Network integrity of the parental brain in infancy ...tive survival function, and are underpinned by brainstem-limbic system connectivity (Burgdorf and Panksepp, 2006). Extant research

Network integrity of the parental brain in infancy

supports the development of childrenrsquos social

competenciesEyal Abraham1 Talma Hendler23 Orna Zagoory-Sharon1 andRuth Feldman14

1Department of Psychology and the Gonda Brain Research Center Bar-Ilan University Ramat-Gan 52900Israel 2Functional Brain Center Wohl Institute of Advanced Imaging Tel-Aviv SouraskyMedical Center TelAviv Israel 3School of Psychological Sciences Faculty of Medicine and Sagol School of Neuroscience Tel AvivUniversity Tel Aviv Israel and 4Child Study Center Yale University School of Medicine New Haven CT USA

Correspondence should be addressed to Ruth Feldman Child Study Center Yale University School of Medicine New Haven CT USAE-mail feldmanruthgmailcom

Abstract

The cross-generational transmission of mammalian sociality initiated by the parentrsquos postpartum brain plasticity andspecies-typical behavior that buttress offspringrsquos socialization has not been studied in humans In this longitudinal studywe measured brain response of 45 primary-caregiving parents to their infantrsquos stimuli observed parentndashinfant interactionsand assayed parental oxytocin (OT) Intra- and inter-network connectivity were computed in three main networks of thehuman parental brain core limbic embodied simulation and mentalizing During preschool two key child social competen-cies were observed emotion regulation and socialization Parentrsquos network integrity in infancy predicted preschoolersrsquo so-cial outcomes with subcortical and cortical network integrity foreshadowing simple evolutionary-based regulatory tacticsvs complex self-regulatory strategies and advanced socialization Parentndashinfant synchrony mediated the links between con-nectivity of the parentrsquos embodied simulation network and preschoolersrsquo ability to use cognitiveexecutive emotion regula-tion strategies highlighting the inherently dyadic nature of this network and its long-term effects on tuning young to sociallife Parentrsquos inter-network core limbic-embodied simulation connectivity predicted childrenrsquos OT as moderated by parentalOT Findings challenge solipsistic neuroscience perspectives by demonstrating how the parentndashoffspring interface enablesthe brain of one human to profoundly impact long-term adaptation of another

Key words parental brain parent-infant synchrony oxytocin embodied simulation mentalizing

Introduction

A key question in the development of social species is howyoung become members of the social group and learn to func-tion competently within the social milieu In highly social spe-cies such as ants or bees young enter social groups via

reciprocal exchanges of sensory stimuli with conspecificsunderpinned by coordination of neuro-hormonal processes(Wilson 2012) In mammals the infantrsquos first social experiencesoccur within the parentndashinfant bond and similarly coordinatebrain and behavior into a process of biobehavioral synchrony(Feldman 2012b 2015b)mdashthe coupling of parentrsquos and infantrsquos

Received 7 February 2016 Revised 25 May 2016 Accepted 20 June 2016

VC The Author (2016) Published by Oxford University PressThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (httpcreativecommonsorglicensesby-nc40) which permits non-commercial re-use distribution and reproduction in any medium provided the original work is properly citedFor commercial re-use please contact journalspermissionsoupcom

1707

Social Cognitive and Affective Neuroscience 2016 1707ndash1718

doi 101093scannsw090Advance Access Publication Date 30 June 2016Original article

Downloaded from httpsacademicoupcomscanarticle-abstract111117072514637by Interdisciplinary Center Herzliya useron 19 April 2018

physiology and behavior during social contactmdashwhich carriesprofound effects for offspringrsquos adaptation (Kundakovic andChampagne 2015) Plasticity of the parental brain in infancyindicated by increased activations of key brain areas implicatedin mammalian parenting accompanied by structural changes inthe parentrsquos brain initiates the cross-generational sequence ofmammalian sociality (Stolzenberg and Numan 2011 Feldman2015b) Research in rodents has shown that the postpartummarks the period of highest plasticity in the adult brain (Cohenand Mizrahi 2015) when areas of the parentrsquos brain includingthe hypothalamus basolateral amygdala parietal cortex andprefrontal cortex partly triggered by oxytocin (OT) release be-come sensitized to infant cues and initiate the expression ofspecies-typical parental behavior (Featherstone et al 2000Lambert et al 2011) These parenting behaviors in turn organ-ize the infantrsquos brain and behavior toward life within the socialecology (Weaver et al 2004 Numan and Young 2016) Imagingstudies of human parentsrsquo brain show activations in parallelareas in response to infant stimuli similarly associated with OTand the human-specific parenting repertoire (Rilling andYoung 2014 Swain et al 2014 Feldman 2015b Kim et al 2016)Yet the cross-generational sequence of mammalian socialityinitiated by adaptation of the parentrsquos brain in infancy continu-ing with the expression of parenting behavior and culminatingin social adaptation of juveniles has not been tested inhumans Describing such sequence in humans may provide evi-dence that the parentndashinfant interface the junction of evolu-tionary progress marks a unique context where one humanrsquosbrain can profoundly affect another humanrsquos social adaptation

Research on the parental brain described three main net-works underpinning human parenting core limbic embodied-simulationempathy and mentalizing (Rilling and Young 2014Swain et al 2014 Feldman 2015b Kim et al 2016) Studies onthe parental brain in rodents detail the critical role of a core-limbic network including the MPOA of the hypothalamusamygdala and subcortical dopamine reward system Primed byOT surge during parturition and sensitized by sensory stimulifrom infant and nest these structures consolidate into a mam-malian parenting network that subserves parenting (Dulac et al2014 Numan and Young 2015) In humans all imaging studiesof infant visuals show that this highly conserved core-limbicnetwork activates with parentsrsquo exposure to their infantsrsquo pic-tures (Atzil et al 2011 Barrett and Fleming 2011 Swain 2011b2012 Abraham et al 2014 Feldman 2015b) However inhumans the ancient limbic network is connected via multipleascending and descending projections to two main cingulo-insular and fronto-temporo-parietal networks that support theflexibility person-specificity and future-directedness of humanparenting (Swain 2011a Rilling and Young 2014) Theembodied-simulationempathy network consists of structuresin the anterior insular-cingulate cortex that enable the parentto resonate with infant state and emotion ground experience inthe present moment and afford perceptual-motor coupling ofinfant action in the parentrsquos brain via mirror mechanisms(Craig 2009 Gallese 2014) The mentalizing network includingfronto-temporo-parietal structures supports social attributionand theory-of-mind abilities (Spunt and Lieberman 2013) andenables parents to understand infantsrsquo nonverbal communica-tions and infer infant intentions from actions (Frith and Frith2006 2012)

The two cortical networks embodied-simulation and men-talization which jointly comprise the human social brain servemultiple cognitive and associative functions and are superim-posed upon the ancient limbic circuit to create the lsquohuman

parental caregiving networkrsquo that integrates immediate motiv-ational responses with the interoceptive and conscious aspectsof human parenting (Swain 2008 Feldman 2015b Kim et al2015) The complexity of the human parental brain and its inte-gration of primitive with later-evolving structures lend supportto the hypothesis that the cross-generational transfer of humansociality likely combines mammalian-general features withuniquely human brain networks and complex parentndashchild ex-changes to facilitate both survival-related and executive-mental child social outcomes

Developmental studies identified two key competencies thatenable preschool children as they enter the social world to so-cially participate with non-kin adults and peers emotion regu-lation and socialization (Kochanska et al 1995 Eisenberg andMorris 2002) Most crucial is emotion regulation defined as theability to manage states of increased negative or positivearousal to facilitate adaptation or goal-directed activity (Coleet al 2004) Research mainly focused on the regulation of nega-tive emotions addressing the development of emotion regula-tion from simple tactics in infancy to more complex strategiesin preschool that require higher socio-cognitive competenciessuch as executive attention or symbolic communications (Foxand Calkins 2003) Emergence of these complex regulatory abil-ities follows the development of anterior insula and ACC con-nectivity at 3ndash4 years and the increase in Von Economoneurons projection cells found mainly in human cingulo-insular cortex that provide the rapid efficient connectivityneeded for mature self-regulation (Allman et al 2005 Posneret al 2014) Regulation of positive emotions the enhancementand maintenance of positive affect draws on simpler mechan-isms like mimicking or self-soothing which comprise part ofthe infantrsquos self-regulatory repertoire from birth serve an adap-tive survival function and are underpinned by brainstem-limbic system connectivity (Burgdorf and Panksepp 2006)Extant research indicated that emotion-regulation abilities arecritical for social adaptation and that preschoolersrsquo ability toregulate emotions is a stable individual trait that predicts cogni-tive social-emotional life-success and mental-health outcomesthroughout life (Eisenberg et al 2000 Moffitt et al 2011)

The second key ability socialization defined as childrenrsquoswilling compliance with adult commands and internalization ofsocial rules undergoes significant maturation during the pre-school years and similarly predicts long-term social adjust-ment mental health and adult employment (Kochanska et al1995 Daly et al 2015) Importantly although preschoolersrsquo emo-tion regulation and socialization may provide an index of life-time adaptation their roots lie in parentndashinfant synchrony(Feldman 2007b Calkins and Hill 2011) Synchronous inter-actions which build online from the parentrsquos and childrsquos non-verbal signals tune the child to social dialogue and providecritical inputs for organizing the brain basis of intersubjectivitya prerequisite of human social life (Feldman 2007c 2012aGallese 2014)

The central question guiding the current study is whetherand how the human parental brain evolved to facilitate key so-cial abilities in human children as in other mammals We as-sessed parentrsquos brain response to own-infant cues usingfunctional magnetic resonance imaging (fMRI) among primary-caregiving first-time mothers and fathers computed intra- andinter- functional connectivity in the aforementioned three net-works based on parentsrsquo brain response to their own infantmeasured parental OT levels and videotaped parentndashinfantinteractions which were coded offline for parentndashinfant syn-chrony Four years later we revisited families observing

1708 | Social Cognitive and Affective Neuroscience 2016 Vol 11 No 11


children in a battery of well-validated emotion-regulation andsocialization paradigms that were micro-coded offline to createmeasures of negative and positive emotional expression use ofsimple and complex regulatory strategies and self-regulated so-cialization OT levels were re-assessed in parent and child

Recent studies in rodents (Bales and Saltzman 2016) andhumans (Abraham et al 2014) demonstrate that different path-ways to the parental brain exist in mothers and fathers yetfathering utilizes similar neural networks as mothering and nodifferences in brain activation levels were found in the threeaforementioned networks between primary-caregiving mothersand fathers We applied a network perspective to the parentalbrain in light of recent models in social neuroscience (Stanleyand Adolphs 2013 Dulac et al 2014 Raz et al 2014) that high-light the need to shift from focusing on activations of discretestructures to coordination of neural circuits that support sociallife Thus theorizing that network connectivity provides a ro-bust index of system functionality we measured connectivityin each network of the lsquohuman parental caregiving networkrsquomdashcore-limbic embodied-simulation and mentalizingmdashand usedthese connectivity indices to predict child outcomes

We hypothesized that network connectivity in the parentrsquosbrain in infancy would shape the childrsquos long-term social com-petencies both directly (Hypothesis 1) and indirectly via parentndashinfant synchrony (Hypothesis 2) We expected that integrity ofthe core-limbic network would support childrenrsquos ability to usesimple evolutionary-based regulatory strategies possibly injoy-related contexts whereas integrity of the parentrsquos corticalnetworks would support advanced self-regulatorysocializationoutcomes that draw on later-evolving executive and inhibitorybrain functions Our special focus centered on the parentrsquosembodied-simulation network which directs the parent tolsquohere-and-nowrsquo bodily exchanges integrates online biologicaland behavioral signals and engages overlapping neural circuitsbetween two individuals (Hasson et al 2012 Decety 2015Hasson and Frith 2016) Such brain-to-brain overlap afforded bythe embodied-simulation network may trigger the expression ofparentndashinfant behavioral synchrony that would tune the in-fantrsquos brain to life within the social world Finally based on re-cent research highlighting the critical role of OT as modulator offunctional connectivity within the social brain (Sokolowski andCorbin 2012 Bethlehem et al 2013) and the cross-generationaltransmission of OT functionality in both humans and othermammals (Meaney 2001 Feldman et al 2010) we expected thatconnectivity among the three networks may support the devel-opment of the childrsquos OT system as mediated by parental OT(Hypothesis 3)

Materials and methodsParticipants

A total of 45 first-time primary-caregiving parents raising theirinfant within a committed two-parent family participated inthe study [mean age 364 years 6 687 sd] These included 20heterosexual primary-caregiving biological mothers and 25homosexual primary-caregiving biological fathers raising theinfant without maternal involvement since birth through surro-gacy Two parents chose not to participate in the follow-uphome visit therefore we excluded their fMRI data Infants[mean age at Time 1 1095 months 6687 sd mean age at Time2 4022 months 6 445 sd] were all born at term and werehealthy since birth (Supplementary Table S1) In all familiesparents were healthy with no history of mental illness and

both parents shared housework and childcare responsibilitiesParticipants received compensation for their time and gavewritten informed consent The study received approval fromthe Institutional Review Board

Procedure

The experimental procedure included three sessions with eachfamily In the first we visited families at home (Time1frac14 Infancy) salivary samples were collected for parental OTand parent was videotaped interacting with the infant In thesecond session several days later primary-caregiving parentunderwent functional brain scanning with the individually tail-ored home videotapes used as fMRI stimuli In the third session(Time 2frac14Preschool) when children reached preschool age were-visited families at home salivary samples were collectedfrom parent and child for OT and preschoolers underwent test-ing with the Stanford-Binet Intelligence Scale (Thorndike et al2003) Visit also included parentndashchild interactions and severalchild emotion-regulation procedures with a stranger videotapedfor later coding when parent was in the room We carefully se-lected well-validated emotion-regulation procedures that tapchildrenrsquos negative and positive emotional expression and theiruse of simple and complex emotion-regulatory strategies asfollows

1 Parent-child free playmdashParent and child engaged in a 7-minfree play session with preselected toys used to elicit play atthis age (Feldman 2007a) Instructions were lsquoPlay with yourchild as you typically dorsquo

2 Self-regulated socializationmdashToy pick-up task (compliancesituation) We employed a well-validated paradigm to assesschildrenrsquos self-regulated socialization and parentrsquos discip-line techniques (Kochanska et al 2001) The parent receiveda cart and instructions to have the child pick up the toys fol-lowing the free play The toy pick-up lasted 8 min or untiltask was completed

3 Regulation of negative emotionsmdashMasks In this procedureadapted from the LAB-TAB (Goldsmith and Rothbart 1996)child sits in front of the experimenter who puts on four in-creasingly fear-eliciting masks rabbit lion alligator andmonster The experimenter wore each mask for 15 s

4 Regulation of positive emotionsmdashBubbles Similarly adaptedfrom the LAB-TAB (Goldsmith and Rothbart 1996) the ex-perimenter blew soap bubbles for the child to play for 5 min

OT collection and determination

Saliva was collected using Salivettes (Sarstedt RommelsdorfGermany) Samples were stored at 20 C until centrifugedtwice 2 days apart at 4 C at 1500g for 20 min Liquid sampleswere kept at 80 C lyophilized for 10 days and stored at 20 COn the assay day the dry samples were reconstituted in waterand concentrated X 4 before immunoassay OT was assayed byELISA (EnzoVR (NY USA) with careful sample preparation sam-ples were centrifuged twice delicate lyophilization maintainedconstant refrigeration to slows the drying and samples werereconstituted in water prior to assay Measurements were per-formed in duplicate and the concentrations of samples werecalculated using Matlab-7 according to relevant standardcurves The intra-assay and inter-assay coefficients of variabil-ity are lt191

E Abraham et al | 1709


Coding

We used global rating scales for parentndashchild interaction at thetwo time-points and micro-coding for child social outcomesmdashemotion regulation and socialization

Parentndashchild interactions (Times 1 and 2) were coded usingthe Coding Interactive Behavior (CIB) Manual (Feldman 1998)This CIB is a well-validated global rating system for adult-childinteractions includes 42 scales which aggregate into theoretic-ally meaningful constructs The system has been validated inmultiple studies and shows good psychometric propertiesincluding testndashretest reliability individual stability across longdevelopmental epochs and construct validity (for review seeFeldman 2012b) In infancy (Time 1) we used the parentndashinfantsynchrony construct was used in infancy to index the centralbehavioral expression of attuned human caregiving Codes de-scribe the expression of the human species-typical parental be-havior (parent gaze positive affect lsquomotheresersquo vocalizationaffectionate touch) and their coordination with the infantrsquos sig-nals (mutual adaptation dyadic reciprocity fluency of the inter-action and the degree to which it provides a supportivepresence for infant play and exploration (Feldman 2007c) Forthe human parental behavior construct we used the four CIBscales that index the human parental caregiving repertoirewhich appears immediately after birth in the gaze affect vocaland touch modalities Codes describe parentsrsquo expression ofwarm and positive affect gaze at infant provision of affectivetouch and high-pitched lsquomotheresersquo vocalizations In preschool(Time 2) we used the child social engagement construct Thisconstruct includes seven scales that measure the degree ofchild social involvement including child alertness social initi-ation affection toward parent symbolic play vocalizationsgaze maintenance and positive affect Trained raters blind to allother information the coding Inter-rater reliability measuredon 20 of the sample was intraclass rfrac14 094 (rangefrac14087ndash099)

Child emotion regulation and socialization The Masks andBubbles paradigms tapping child emotion regulation wereeach micro-coded for the childrsquos expression of positive emotion-ality (positive affect positive vocalizations and laughter) andnegative emotionality (negative affect withdrawal cryingyell-ing and protest) Two types of regulatory behaviors were micro-coded consistent with prior research (Feldman et al 2011Hirschler-Guttenberg et al 2015 Ostfeld-Etzion et al 2015)Simple regulatory behaviorsmdashincluded behaviors aiming solelyat self-regulation that clearly display the childrsquos regulatory ef-fort such as physical self-soothing (eg thumb-sucking) verbalself-soothing (eg lsquoThatrsquos okayrsquo) and proximity seekingComplex regulatory behaviorsmdashincluded complex behaviorsthat are not inherently self-regulatory but may be used for emo-tion regulation during moments of increased stress such assubstitutive-symbolic play functional play using executiveskills to divert attention or talking to parent or experimenter

The Toy pick-up paradigm aimed to index child socializa-tion was micro-coded consistent with prior research(Kochanska and Aksan 1995 Feldman et al 1999) for child self-regulated compliance and parentrsquos discipline techniquesParent codes included warm controlmdashparent shows positive af-fect while providing consistent limits uses tactics such as en-couragement redirection of attention or praise negotiates withthe child explains and suggests and shows empathy in orderto keep child on task harsh controlmdashparent uses physical forceinsults yelling or manipulations no controlmdashparent providesno structure lets child do as he or she pleases with no attention

to task may pick up the toys for child Coding was conductedon a computerized system (The Observer Noldus InformationTechnology Wageningen The Netherlands) Two blind trainedobserverscoded while the tape progressed at normal speedshifting to slow motion when shift in behavior occurred Coderswere trained to 90 reliability Inter-rater reliability measuredon 20 of the sample was intraclass rfrac14 091 for the pick-upprocedure rfrac14 086 for the masks and rfrac14 089 for the bubblesProportion and frequency variables were used

fMRI data acquisition and analyses

Imaging was performed on a GE-3T Sigma Horizon echo-speedscanner with a resonant gradient echoplanar imaging systemFunctional T2-weighted images were obtained using field ofviewfrac14 220 mm matrix sizefrac14 96 96 repetition timefrac14 3000 msecho timefrac14 35 ms flip anglefrac14 90 acquisition orientation of thefourth ventricle plane 39 axial slices of 3-mm thickness andgapfrac14 0 In addition each functional scan was accompanied by athree-dimensional (3D) anatomical scan using anatomical 3Dsequence spoiled gradient (SPGR) echo sequences that were ob-tained with high-resolution of 1 1 1 mm fMRI data wereanalyzed with the BrainVoyager analysis package (version 21Brain Innovation)

fMRI data preprocessing

The first six volumes before signal stabilization were discardedto allow for T1 equilibrium Preprocessing of functional scansincluded 3D motion correction slice scan time correction spa-tial smoothing [a full width at half maximum 4-mm GaussianKernel] linear trend removal and high-pass filtering (fastFourier transform based with a cutoff of two cycles per timecourse) The functional images were then superimposed on 2Danatomical images (a 3D SPGR echo sequence field of view-frac14 220 mm matrix sizefrac14 96 96 axial slices of 3 mm thicknessgapfrac14 0) and incorporated into the 3D datasets through trilinearinterpolation The complete dataset was transformed intoTalairach space

fMRI experimental design

While lying in the scanner participants were instructed towatch a series of attachment-related video vignettes presentedon the screen For ecological validity we examined parentsrsquobrain response to natural interactions and attachment-relatedstimuli videotaped in the home environment the contextwhere parentalndashinfant bonding takes place All videos includedmulti-modal dynamic and realistic stimuli Each parentrsquos videoset was individually tailored comprising three 2-min infant-and parent-related videos with alternating rest fixation periodsof 15 or 18 s between stimuli preceded by a 1-min rest with fix-ation period For the NCI analysis we used a 2 min vignette ofeach parent interacting with herhis own infant (lsquoSelfndashInfantInteractionrsquo) Stimuli were counterbalanced and were randomlypresented in three different order patterns To ensure our re-sults describe parentsrsquo networks integrity stimulated specific-ally by observing themselves interacting with their infant wecomputed NCI analysis for a 2 min lsquounfamiliar parentndashinfantinteractionrsquo condition (in which the parent was of the same sexas the participant) and found no significant links to any childsocial outcomes In addition we found specific associations be-tween child social outcomes and a parental network but not



with the other network analyses which provide convincing evi-dence for the specific role these parental networks play duringinfancy in supporting childrenrsquos long-term social developmentTo ensure that parents and infantsrsquo affective states did not dif-fer between participants we selected only clips in which the in-fants and the parents were in neutral or positive affectivestates as coded using the CIB rating system

Computation of network cohesion indices

To analyzing the dynamic functional network connectivity ofthe three brain networks of interest we used a NCI index (fordetails see Raz et al 2012 2014) probing the dynamics of coord-ination both within defined network (intra-network cohesionindex intra-NCI) and between networks (inter-network cohe-sion index inter-NCI) Cohesion is measured here in a way thatreflects both the strength of the average correlations betweensignals in a group of regions and the variation around this aver-age with higher values for correlations that are narrowly dis-tributed around a high average First the average signal of eachregion-of-interest (ROI) was extracted using a Gaussian maskwith 3 mm radius around the seed coordinates in a selectedtime window of 114 s (38 TRs) the lsquoSelfndashInfant Interactionrsquo con-dition incorporating a hemodynamic delay of two TRs Next foreach network k and participant p the set of all pairwisePearson correlations was computed at the selected time-window t as follows

NCIpk teth THORN frac14 tstatistic qp

ij teth THORN j i j 2 network kn o

(1)

Thus the NCI resulted from a right tailed Studentrsquos t-testwith a null hypothesis of mRfrac14 0 performed on the population ofthe Fisher Z-transformed coefficients In this test the t-statisticserves as a probe for the connectivity within the network withhigh values when the mean correlation is high and variance islow Inter-NCI was calculated in the same manner except thatthe population of the t-tested pairwise correlations includespairs of ROIs in different networks

Definition of networks of interest

Relevant comprehensive and updated meta-analyses of neuroi-maging studies were used to define core-limbic embodied-simulationempathy and mentalizing networks (Figure 2 andSupplementary Table S2) The three chosen networks core-limbic embodied-simulationempathy and mentalizing havebeen repeatedly shown in studies on the parental brain tounderpin human parenting and all brain structures within thesenetworks have been found in previous research to activate in re-sponse to infant cues (auditory visual or multimodal infantstimuli such as infant crying pictures or movies often com-prising lsquoownrsquo infant to standard infant or control condition)(Swain 2008 Rilling and Young 2014 Swain et al 2014Feldman 2015b Kim et al 2016) The core-limbic network wasdefined on the basis of a meta-analysis that clustered emotion-related brain structures according to their co-activity acrossstudies (Kober et al 2008) The embodied-simulationempathynetwork was defined on the basis of recent meta-analyses onempathy (Fan et al 2011) and mirror properties (Molenberghset al 2012) The mentalizing network was based on in whichparticipants were instructed to infer othersrsquo intentionsthoughts and future actions (Bzdok et al 2012) MontrealNeurological Institute (MNI) to Talairach transformations were

performed using a Lancaster transformation (Lancaster et al2007)

ResultsAssociations between parental behaviors and child socialoutcomes

Consistent with ethological perspectives we first sought toexamine associations between parental behaviors in infancyand childrsquos social outcomes during the preschool period Sinceno differences emerged between preschoolers reared byprimary-caregiving mothers vs fathers on any preschool vari-able (Supplementary Table S2) we collapsed the two groupsThe Human parental behavior construct including affectivetouch lsquomotheresersquo vocalization gaze and positive affectmdasha con-struct that parallels the licking-and-grooming of other mam-malsmdashwas longitudinally related to the childrsquos use of simpleregulatory strategies in preschool (rfrac14 0395 Pfrac14 0007) Parentndashinfant synchrony in infancy was longitudinally associated withthe childrsquos employment of complex regulatory strategies in pre-school (rfrac14 0505 Pfrac14 00001) Finally higher parental warm con-trol behavior defining the integration of warm affect with clearlimits was associated with childrsquos self-regulated socializationin preschool (rfrac14 0352 Pfrac14 0018)

Direct links between parentrsquos intra-network integrity andchild social outcomes

We defined the three networks of the parental brain on thebasis of prior research (Figure 1A and B Supplementary TableS3) To dynamically examine parentsrsquo functional connectivitywithin networks as activated while viewing their videotapedinteractions with their infant we applied network cohesionanalysis (NCI Raz et al 2012 2014) to derive intra-network indi-ces No differences emerged in intra-connectivity betweenprimary-caregiving mothers and fathers in any of the three net-works Core-limbic-NCI F143frac140281 Pfrac14 0599 Embodied-simulation-NCI F143frac14008 Pfrac14 0778 Mentalizing-NCI F143frac140821 Pfrac14 0370 (Figure 1C) Thus we collapsed the mother andfather groups To test direct links between parental brain andchild outcomes (Hypothesis 1) ANOVAs measured differencesin child outcomes at Time 2 among parents with high vs lowNCI in each network using the median split Results indicatethat preschoolers raised by parents with greater connectivity inthe core-limbic network (Figure 2A medianfrac14 0264) exhibitedmore positive emotionality (F143frac14438 Pfrac14 0037) readilyemployed simple regulatory strategies such as mimicking andself-soothing (F143frac14615 Pfrac14 0017) and displayed greater socialengagement during interaction with their parents (F143frac14549Pfrac14 0023) Second as predicted preschoolers whose parents ex-hibited higher connectivity of the embodied-simulation net-work (Figure 2B medianfrac14 0288) exhibited less negativeemotionality (F143frac14430 Pfrac14 0043) and utilized complex regula-tory strategies to regulate the negative context (F143frac14688 Pfrac14 0012) including executive attention and symbolic communica-tion Finally preschoolers of parents with greater connectivityof the mentalizing network (Figure 2C medianfrac14 0108) dis-played greater self-regulated socialization when asked to com-ply to adultsrsquo requests (F143frac14427 Pfrac14 0041) (SupplementaryTables S4ndashS6)



Indirect effects of parentrsquos intra-network integrity on childoutcomes

To test Hypothesis 2 on indirect effects via parenting behaviorwe examined whether parental behavior mediated the relation-ship between parentrsquos intra-NCIs and childrsquos social outcomesfor each network separately As predicted using Sobelrsquos (1982)test we found partial mediation by parentndashinfant synchro-nyonly for the link between parentrsquos embodied-simulation-NCIand preschoolersrsquo complex regulatory behaviors (zfrac14 2210Pfrac14 0027 Figure 3) Baron and Kennyrsquos (1986 see Figure 3A)steps were computed In Step 1 associations between the pre-dictor (parentrsquos embodied-simulation-NCI) and outcome (childcomplex regulation) was found significant (path C szligfrac14 05tfrac14 3785 Pfrac14 0001) In Step 2 associations between predictorand mediator (parentndashinfant synchrony) were significant (pathA szligfrac14 0382 tfrac14 2707 Pfrac14 0009) In Step 3 associations betweenmediator and outcome controlling for predictor were significant(path B szligfrac14 368 tfrac14 2764 Pfrac14 0008) In Step 4 we associationpredictor and the outcome controlling for mediator were

significant (szligrsquofrac140360 tfrac14 2704 Pfrac14 001) Sobelrsquos test for medi-ation zfrac14 2210 Plt 005 indicated a significant indirect effect ofparentrsquos embodied-simulation-NCI on the childrsquos use of com-plex regulatory behaviors 4 years later partially mediated byparentndashinfant synchrony

Associations between parentrsquos inter-network connectivityand child OT

Finally to provide a system-level perspective on the parentalbrain and its effects on children we assessed inter-connectivity(inter-NCIrsquos) between networks comprising the lsquohuman parentalcaregiving networkrsquo Results indicate that the connectivity be-tween parentrsquos core-limbic and embodied simulation-inter-NCIin infancy predicted childrenrsquos OT levels at preschool(Hypothesis 3) (rfrac14 0499 Pfrac14 00001) Interestingly we found thatparentrsquos OT level in infancy moderated the relation betweenparentrsquos core limbic-embodied simulation-NCI and childrsquos OTlevels (R2 Totalfrac14 0367 F141frac147909 Pfrac14 0001 Figure 3BSupplementary Table S7) A hierarchical multiple regression

Fig 1 Location of ROIs comprising the core-limbic (red) embodied-simulation (green) and mentalizing (blue) networks from coronal (A) and sagittal (B) views

dmPFC dorsomedial prefrontal cortex Ant insula anterior insula IFG inferior frontal gyrus TP temporal pole NAcc nucleus accumbens GP globuspallidus STS su-

perior temporal sulcus TPJ temporoparietal junction PAG periaqueductal gray vmPFC ventromedial prefrontal cortex ACC anterior cingulated cortex L left R

right The bar graph (C) presents the three networksrsquo intra-NCI values (6SE represented by error bars at top) activated by parentsrsquo viewing of their interactions with in-

fants at Time 1 for primary-caregiving mothers (PC-Mothers nfrac14 20 bright orange) and primary-caregiving fathers (PC-Fathers nfrac1425 dark orange)



predicting childrenrsquos OT by parentrsquos core limbic-embodiedsimulationndashNCI parentrsquos OT and their interaction showedchildrenrsquos OT was independently predicted by parentrsquos corelimbic-embodied simulation-NCI and the interaction of thisconnectivity with parentrsquos OT Under condition of high parentalOT levels (above and below the median split medianfrac14 2934)significant positive correlation emerged between parentsrsquo corelimbic-embodied simulation-NCI and childrsquos OT levels (rfrac14 0677Pfrac14 00001) but such correlation was not found under low par-entrsquos OT (rfrac14 005 Pfrac14 0831) Higher childrsquos OT was associatedwith more frequent child use of complex regulatory strategies(rfrac14 0447 Pfrac14 0002)

Discussion

This study provides the first evidence that functionality of thehuman parental brain in infancy as expressed in network in-tegrity bears long-term impact on key social abilities in humanchildren and on the neurohormonal substrate that supportsmammalian sociality We found that this effect was both directand mediated by context-specific and skill-specific parental be-havior and parentsrsquo hormones reflecting the specificity andcomplexity of human social functions Our study is the first touse integrity indices in the three main networks comprising thelsquohuman parental caregiving networkrsquo to test functionality of the

Fig 2 Relations between parentrsquos intra-NCIs and childrsquos emotion regulation emotionality and social behaviors (Time 2) Proportion values (6SE represented by error

bars at the top) are presented for childrsquos simple regulatory behaviors and positive emotionality during positive-emotion-eliciting paradigm and childrsquos social behavior

during parentndashchild interaction (A) childrsquos complex regulatory behaviors and negative emotionality during negative-emotion-eliciting paradigm (B) and childrsquos self-

regulatory socialization during socialization situation (C) nfrac1445 Plt 005



human parental brain This is also the first study to follow par-ents and infants across the first 4 years of life to examine long-term effects of the parentrsquos brain adaptation in infancy on thesocial outcomes of juveniles as measured by direct observationsof key social competencies and hormonal assessments Wefound specific links between network integrity in the parentrsquosbrain in infancy and key social competencies in human chil-dren similar to that found in other mammals Specifically in-tegrity of the parentrsquos subcortical network was associated withthe childrsquos expression of positive emotionality and use of sim-ple mammalian-general regulatory behavior whereas integrityof the parentrsquos cortical networks was linked with the develop-ment of human-specific sociocognitive skills including com-plex emotion regulation and self-regulated socializationFinally functional connectivity between the parentrsquos subcor-tical and embodied-simulation networks was longitudinallylinked with the childrsquos OT levels OT is implicated in multiplesocial abilities in children adolescents and adults including so-cial reciprocity empathy trust mind-reading and emotion de-tection (Bartz et al 2011 Feldman et al 2013 Gordon et al 2013De Dreu and Kret 2016) Overall our findings underscore one

pathway by which the neurobiology of parenting shapes the so-cial development of human children

It has long been suggested that the parentndashinfant interfaceprovides the template for species continuity and evolutionarychange via reciprocal social behavior (Tinbergen 1963) Ourfindings provide evidence for such cross-generational mechan-isms in humans by charting longitudinal links from network in-tegrity of the parentrsquos brain in infancy and two critical childsocial competencies in preschool-aged children as measured byobservation of social behavior toward a non-kin conspecificThese critical social competenciesmdashemotion regulation and so-cializationmdashare individually stable and predict the individualrsquoslifetime adaptation to the social world from social cognition toadultsrsquo employment history (Moffitt et al 2011 Fox and Pine2012 Daly et al 2015) Overall our findings show that the integ-rity of the human parental brain in the postpartum confers evo-lutionary advantage to human children similar to thatdescribed for other mammals (Rilling and Young 2014 Nguyenet al 2015) The complexity and multifinality of the humanbrain and social behavior is thus reflected in our studyrsquosfindings

Fig 3 Direct and indirect effects of parentrsquos-NCI on childrsquos outcomes (Time 2) Standardized regression coefficient for the relations between parentrsquos embodied-simu-

lation-NCI and childrsquos complex self-regulation as partially mediated by parent-infant synchrony Path c shows the standardized regression coefficient for the total (b)

and direct (brsquo) effects of embodied-simulation-NC Ion childrsquos complex regulatory behavior (A) Moderation model of parental OT levels on core limbic and embodied

simulation-Inter-NCI and childrsquos OT levels Path b Model shows the standardized regression coefficient for the interaction (b) and direct (brsquo) effects of core (there was

no space) limbic-embodied simulation-Inter-NCI on childrsquos OT levels Examination of the interaction showed that under condition of high parental OT levels a signifi-

cant positive correlation was found between parentsrsquocore limbic-embodied simulation-inter-NCI and childrsquos OT (solid line) and was not found under low parental

OT levels (broken line) In addition higher childrsquos OT levels were positively associated with more frequent child use of complex regulatory strategies (B) Plt 005

Plt 001 Plt 0001



Consistent with animal studies that demonstrate the criticalrole of early parental behavior for social development of theyoung (Meaney 2001 Braun and Champagne 2014) our resultsdescribe the links between human parental behavior and youngchildrenrsquos emotion regulation and socialization The humanparental postpartum repertoire comprising the non-verbalbuilding blocks of human social exchange in the gaze affectvocal and touch modalities was longitudinally related to chil-drenrsquos use of regulatory strategies to manage moments of higharousal This is consistent with animal studies indicating thatearly somatosensory and olfactory experiences bear lifetime ef-fects on offspring (Lovic et al 2001) In addition parentndashinfantsynchrony the coupling of parent and childrsquos social signals in-tentions and communications predicted the childrsquos use of com-plex regulatory strategies Such findings are in line withlongitudinal studies indicating that the experience of inter-active synchrony in the first months of life shapes a host ofhuman-specific functions in children and adolescents includ-ing complex socialization symbolic competence and the cap-acity for empathy (Feldman 2007b Calkins and Hill 2011)Finally the parentrsquos warm-control discipline tactics correlatedwith child self-regulated socialization according with perspec-tives that emphasize the importance of the parentrsquos warmthand clear limits for child socialization (Kochanska et al 1995Feldman and Klein 2003)

Integrity of the parentrsquos core-limbic network which supportsmammalian parenting (Numan 2012 Kumi and Numan 2014)and is characterized by high postpartum plasticity (Kim et al2010 Leuner et al 2010 Abraham et al 2014 Royle et al 2014)was found to predict the childrsquos greater skills at maintainingpositive emotionality by employing simple mammalian-general strategies These results which highlight some cross-generational origins parallel findings on increases in c-Fosexpression in the limbic system of juvenile rats during positivesocial play (van Kerkhof et al 2013) In humans research hasshown that the regulation of negative and positive emotions isunderpinned by distinct mechanisms (Feldman 2003Hirschler-Guttenberg et al 2015) and that positive emotionalityand social engagement in preschool predict a host of positiveoutcomes and greater success in social groups throughout life(Porges 2003 Dougherty et al 2010)

In contrast the more complex human-specific social skillssuch as attention manipulation symbolization in the service ofemotion regulation and internalization of social rules that buildon sociocognitive skills and theory-of-mind capacities de-pended on the integrity of the parentrsquos embodied-simulationand mentalizing networks These networks enable humans toshare intentions and experiences during online social inter-actions (Frith and Frith 2012) and their functioning has beenshown to motivate empathic-related prosocial behavior ineveryday life (Rameson et al 2011) Preschoolers of parents withgreater embodied-simulation connectivity displayed lowernegative emotionality which has been linked with greater so-cial competence (Eisenberg et al 2000) and greater use of com-plex regulatory strategies abilities that characterize childrenwith advanced social skills and lower psychopathology(Hirschler-Guttenberg et al 2015 Ostfeld-Etzion et al 2015)Finally preschoolers of parents who displayed higher connect-ivity of the mentalizing network exhibited higher self-regulatedsocialization Self-regulated socialization in the preschool yearsdevelops on the basis of synchronous parentndashchild interactionsin infancy and supports in turn the emergence of higher-ordersocial competencies in later childhood and adolescence(Kochanska et al 1995 Feldman et al 1999 Feldman 2007b)

Of special interest is the finding that parentndashinfant syn-chrony mediated the longitudinal link between integrity of theparentrsquos embodied-simulation network in infancy and pre-schoolersrsquo complex emotion-regulation skills This accords withbiobehavioral perspectives suggesting that the brainrsquos embod-ied-simulation network builds upon early social experiences(Keysers and Gazzola 2007 Gallese 2014) particularly thoseinvolving the coordination of visual and motor signals into ajoint brain-to-brain unit (Hasson et al 2015) The embodied-simulation network is dyadic in nature and contains cellularand molecular mechanisms that bind two brains throughparallel activity and integrate first-person experience and third-person observation (Keysers et al 2013 Decety 2015)It integrates online biological and behavioral signals betweensocial partners (Gallese 2015) thus potentially shaping the in-fantrsquos social brain and the use of complex behavior to navigatethe social world Parentndashinfant synchrony provides the firstpractice of such intersubjective mechanisms through the part-nersrsquo online matching of sensory-motor social cues during mo-ments of social contact (Feldman 2012a) Parentndashinfantsynchrony in infancy provides the foundation for the childrsquos so-cial development and shapes the lifelong capacity to regulatestress modulate arousal and engage in coordinated social inter-actions with intimate partners and strangers abilities whichare critical for human participation in social life (Feldman2015a) Research has shown that parentndashinfant synchrony pre-dicts the development of children emotion regulation attach-ment security physiological organization and empathy acrosschildhood and adolescence (Feldman 2007a 2015a Beebe et al2010) Moreover the experience of biobehavioral synchrony thecoupling of physiology and behavior in parent and child organ-izes the infantrsquos physiological systems including the OT sys-tem to enable parenting in the next generation therebysupporting the cross-generation transmission of human attach-ment (Feldman et al 2010) Our findings may suggest thatembodied-simulation mechanisms in the parentrsquos brain utilizesynchronous interactions to tune the infantrsquos brain to social lifepossibly via mechanisms that involve dynamic coordination be-tween two brains (Ames et al 2014 Hasson and Frith 2016)With the maturation of cingular and frontal corticesrsquo connectiv-ity this early tuning enables children to reach more complexsocial outcomes such as the internalization of social rules be-havior inhibition and use of symbolic acts to regulate emotions

In addition to intra-network connectivity we found thatinter-network connectivity between the parentrsquos subcorticaland embodied-simulation network was longitudinally associ-ated with the development of childrenrsquos OT response as medi-ated by the parentrsquos OT in infancy This is consistent withrecent brain studies demonstrating enhanced functional con-nectivity between the amygdala and the ACC and anterior in-sula under OT administration (Bos et al 2012 Riem et al 2012Rilling et al 2012) Findings is also consistent with research inanimal models (Ross and Young 2009) showing that connectiv-ity between limbic and cortical networks in the parentrsquos brainshaped childrenrsquos OT response which in turn supported matur-ation of the childrsquos social competencies Overall our results areconsistent with multiple perspectives highlighting the integra-tive nature of this ancient peptidergic system and its reorgan-ization by early attachment experiences (Ludwig and Leng2006 Feldman et al 2016)

This study should be considered in light of its limitationsFirst it is possible that other unmeasured factor such as sharedgenes contributed to the longitudinal effects In addition oursample includes parents of middle- to high-socioeconomic



backgrounds with no reported parental psychopathology andfuture studies are need to generalize the findings to other popu-lations including parents at higher risk

Overall our findings challenge the solipsistic viewpointguiding most human neuroscience research and highlight theembedded nature of the human brain We further suggest thatthe human parentndashinfant interface provides the prototypicalcontext for such embeddedness and that it carries profound ef-fects on offspringrsquos survival and thriving Much further researchintegrating brain hormones and behavior in the context of theparentndashinfant unit is required to better understand the dynamiccoupling of parentrsquos and infantrsquos brains and its long-term effectson the development of infant social adaptation Our findingsmay provide a first step toward addressing the gap between in-dividuals by describing how intersubjectivity implements in theparentrsquos brain and transmits to offspring to facilitate greateradaptation to human social life

Supplementary data

Supplementary data are available at SCAN online

Conflict of interest None declared

Acknowledgements

Special thanks to Dr Gal Raz (the Tel Aviv Center for BrainFunction) for providing the scripts and overall guidance forthe network analysis using the NCI algorithm and to shimritsolnik for invaluable assistance with the NCI implementa-tion Supported by the German-Israeli Foundation (1114-10522010) the Simms-Mann Foundation and the Irving BHarris Foundation and the I-CORE Program of the Planningand Budgeting Committee and The Israel ScienceFoundation (grant No 5111)to RF Thanks for the fundingof the Sagol network foundation (to TH) the Israel Centersof Research Excellence for cognitive studies (no 5111 toTH) and the Israeli Ministry of Science Technology andSpace (Grant no 3-11170 to TH)

ReferencesAbraham E Hendler T Shapira-Lichter I Kanat-Maymon Y

Zagoory-Sharon O Feldman R (2014) Fatherrsquos brain is sensi-tive to childcare experiences Proceedings of the NationalAcademy of Science United States of America 111 9792ndash7

Allman JM Watson KK Tetreault NA Hakeem AY (2005)Intuition and autism a possible role for Von Economo neu-rons Trends in Cognitive Sciences 9 367ndash73

Ames DL Honey CJ Chow MA Todorov A Hasson U(2014) Contextual alignment of cognitive and neural dy-namics Journal of Cognitive Neuroscience 27 655ndash64

Atzil S Hendler T Feldman R (2011) Specifying the neurobio-logical basis of human attachment brain hormones and behaviorin synchronous and intrusive mothers Neuropsychopharmacology36 2603ndash15

Bales KL Saltzman W (2016) Fathering in rodents neurobio-logical substrates and consequences for offspring Hormonesand Behavior 77 249ndash59

Barrett J Fleming AS (2011) Annual research review all moth-ers are not created equal neural and psychobiological per-spectives on mothering and the importance of individualdifferences Journal of Child Psychology and Psychiatry 52 368ndash97

Bartz JA Zaki J Bolger N Ochsner KN (2011) Social effectsof oxytocin in humans context and person matter Trends inCognitive Sciences 15 301ndash9

Beebe B Jaffe J Markese S et al (2010) The origins of 12-monthattachment a microanalysis of 4-month motherndashinfant inter-action Attachment and Human Development 12 3ndash141

Bethlehem RAI van Honk J Auyeung B Baron-Cohen S(2013) Oxytocin brain physiology and functional connectiv-ity a review of intranasal oxytocin fMRI studiesPsychoneuroendocrinology 38 962ndash74

Bos PA Panksepp J Bluthe RM Honk J V (2012) Acute ef-fects of steroid hormones and neuropeptides on humansocialndashemotional behavior a review of single administrationstudies Frontiers in Neuroendocrinology 33 17ndash35

Braun K Champagne FA (2014) Paternal influences on off-spring development behavioural and epigenetic pathwaysJournal of Neuroendocrinology 26 697ndash706

Burgdorf J Panksepp J (2006) The neurobiology of positiveemotions Neuroscience and Biobehavioral Reviews 30 173ndash87

Bzdok D Schilbach L Vogeley K et al (2012) Parsing the neu-ral correlates of moral cognition ALE meta-analysis on mor-ality theory of mind and empathy Brain Structure and Function217(4) 783ndash96

Calkins S Hill A (2007) Caregiver Influences on EmergingEmotion Regulation In Gross JJ editor Handbook of EmotionRegulation New York Guilford Press 229ndash48

Cohen L Mizrahi A (2015) Plasticity during motherhoodchanges in excitatory and inhibitory layer 23 neurons in audi-tory cortex The Journal of Neuroscience 35 1806ndash15

Cole PM Martin SE Dennis TA (2004) Emotion regulationas a scientific construct methodological challenges and direc-tions for child development research Child Development 75317ndash33

Craig AD (2009) How do you feel now The anterior insula andhuman awareness Nature Reviews Neuroscience 10 59ndash70

Daly M Delaney L Egan M Baumeister RF (2015) Childhoodself-control and unemployment throughout the life span evidencefrom two British cohort studies Psychological Science 26 709ndash23

De Dreu CKW Kret ME (2016) Oxytocin conditions intergrouprelations through upregulated in-group empathy cooperationconformity and defense Biological Psychiatry 79 165ndash73

Decety J (2015) The neural pathways development and func-tions of empathy Current Opinion in Behavioral Sciences 3 1ndash6

Dougherty LR Klei DNEmilyhayden C Elizabeth PThomas M (2010) Temperamental positive and negativeemotionality and childrenrsquos depressive symptoms a longitu-dinal prospective study from age three to age ten Journal ofSocial and Clinical Psychology 29 462ndash88

Dulac C OrsquoConnell LA Wu Z (2014) Neural control of mater-nal and paternal behaviors Science 345 765ndash70

Eisenberg N Fabes RA Guthrie IK Reiser M (2000)Dispositional emotionality and regulation their role in pre-dicting quality of social functioning Journal of Personality andSocial Psychology 78 136ndash57

Eisenberg N Morris AS (2002) Childrenrsquos emotion-related reg-ulation Advances in Child Development and Behavior 30 189ndash229

Fan Y Duncan NW de Greck M et al (2011) Is there a coreneural network in empathy An fMRI based quantitativemeta-analysis Neuroscience amp Biobehavioral Reviews 35(3)903ndash11

Featherstone RE Fleming AS Ivy GO (2000) Plasticity in thematernal circuit effects of experience and partum conditionon brain astroctye number in female rats BehavioralNeuroscience 114 158ndash72



Feldman R (1998) Mother-Newborn Coding System Manual TelAviv Israel Bar-Ilan University Press

Feldman R (2003) Infantndashmother and infantndashfather synchronythe coregulation of positive arousal Infant Mental HealthJournal 24 1ndash23

Feldman R (2007a) Mother-infant synchrony and the develop-ment of moral orientation in childhood and adolescence dir-ect and indirect mechanisms of developmental continuityAmerican Journal of Orthopsychiatry 77 582ndash97

Feldman R (2007b) Parentndashinfant synchrony and the construc-tion of shared timing physiological precursors developmentaloutcomes and risk conditions Journal of Child Psychology andPsychiatry 48 329ndash54

Feldman R (2007c) Parentndashinfant synchrony biological founda-tions and developmental outcomes Current Directions inPsychological Science 16 340ndash5

Feldman R (2012a) Bio-behavioral synchrony a model for inte-grating biological and microsocial behavioral processes in thestudy of parenting Parenting 12 154ndash64

Feldman R (2012b) Parenting Behavior as the EnvironmentWhere Children Grow In Mayes LC Lewis M editors TheCambridge Handbook of Environment in Human Development NewYork Cambridge University Press 535ndash67

Feldman R (2015a) Sensitive periods in human social develop-ment new insights from research on oxytocin synchrony andhigh-risk parenting Development and Psychopathology 27 369ndash95

Feldman R (2015b) The adaptive human parental brain impli-cations for childrenrsquos social development Trends inNeurosciences 38 387ndash99

Feldman R Dollberg D Nadam R (2011) The expression andregulation of anger in toddlers relations to maternal behaviorand mental representations Infant Behavior and Development34 310ndash20

Feldman R Gordon I Influs M Gutbir T Ebstein RP (2013)Parental oxytocin and early caregiving jointly shape childrenrsquosoxytocin response and social reciprocity Neuropsychopharmacology38 1154ndash62

Feldman R Gordon I Zagoory-Sharon O (2010) The cross-generation transmission of oxytocin in humans Hormones andBehavior 58 669ndash76

Feldman R Greenbaum CW Yirmiya N (1999) Mother-infantaffect synchrony as an antecedent of the emergence of self-control Development and Psychopathology 35 223ndash31

Feldman R Klein PS (2003) Toddlersrsquo self-regulated compli-ance to mothers caregivers and fathers implications for theo-ries of socialization Development and Psychopathology 39 680ndash92

Feldman R Monakhov M Pratt M Ebstein RP (2016)Oxytocin pathway genes evolutionary ancient system impact-ing on human affiliation sociality and psychopathologyBiological Psychiatry 79 174ndash84

Fox NA Calkins SD (2003) The development of self-control ofemotion intrinsic and extrinsic influences Motivation andEmotion 27 7ndash26

Fox NA Pine DS (2012) Temperament and the emergence ofanxiety disorders Journal of the American Academy of Child andAdolescent Psychiatry 51 125ndash8

Frith CD Frith U (2006) The neural basis of mentalizingNeuron 50 531ndash4

Frith CD Frith U (2012) Mechanisms of social cognitionAnnual Review of Psychology 63 287ndash313

Gallese V (2014) Bodily selves in relation embodied simulationas second-person perspective on intersubjectivityPhilosophical Transactions of the Royal Society of London Series BBiological Sciences 369 20130177

Gallese V (2015) Embodied simulation as second-person per-spective on intersubjectivity In Jan De Vos Ed Pluth editorsNeuroscience and Critique Exploring the Limits of NeurologicalTurns New York Routledge 188ndash203

Goldsmith HH Rothbart MK (1996) The LaboratoryTemperament Assessment Battery Locomotor Version 30Technical Manual Madison WI University of Wisconsin

Gordon I Wyk BCV Bennett RH et al (2013) Oxytocin en-hances brain function in children with autism Proceedings of theNational Academy of Science United States of America 110 20953ndash8

Hasson U Janice C Christopher JH (2015) Hierarchical proc-ess memory memory as an integral component of informa-tion processing Trends in cognitive sciences 196 304ndash13

Hasson U Frith CD (2016) Mirroring and beyond coupled dy-namics as a generalized framework for modelling social inter-actions Philosophical Transactions of the Royal Society of LondonSeries B Biological Sciences 371 20150366

Hasson U Ghazanfar AA Galantucci B Garrod S KeysersC (2012) Brain-to-brain coupling a mechanism for creatingand sharing a social world Trends in Cognitive Sciences 16114ndash21

Hirschler-Guttenberg Y Feldman R Ostfeld-Etzion S LaorN Golan O (2015) Self- and co-regulation of anger and fear inpreschoolers with autism spectrum disorders the role of ma-ternal parenting style and temperament Journal of Autism andDevelopmental Disorders 45 1ndash11

Keysers C Gazzola V (2007) Integrating simulation and theoryof mind from self to social cognition Trends in CognitiveSciences 11 194ndash6

Keysers C Thioux M Gazzola V (2013) Mirror neurons sys-tem and social cognition In Baron-Cohen S Lombardo MTager-Flusberg H Cohen D editors Understanding OtherMinds Perspectives from Developmental Social NeuroscienceOxford Oxford University Press 233ndash64

Kim P Leckman JF Mayes LC Feldman R Wang X SwainJE (2010) The plasticity of human maternal brain longitudi-nal changes in brain anatomy during the early postpartumperiod Behavioral neuroscience 124(5) 695ndash700

Kim HE Torres-Garcia A Swain JE (2015) The parental braina neural framework for study of teaching in humans and otheranimals The Behavioral and Brain Sciences 38 28ndash9

Kim P Strathearn L Swain JE (2016) The maternal brain andits plasticity in humans Hormones and Behavior 77 113ndash23

Kober H Barrett LF Joseph J Bliss-Moreau E Lindquist KWager TD et al (2008) Functional grouping and corticalsub-cortical interactions in emotion a meta-analysis of neuroi-maging studies Neuroimage 42(2) 998ndash1031

Kochanska G Aksan N (1995) Mother-child mutually positiveaffect the quality of child compliance to requests and prohib-itions and maternal control as correlates of early internaliza-tion Child Development 66 236ndash54

Kochanska G Aksan N Koenig AL (1995) A longitudinalstudy of the roots of preschoolersrsquo conscience committedcompliance and emerging internalization Child Development66 1752ndash69

Kochanska G Coy KC Murray KT (2001) The developmentof self-regulation in the first four years of life ChildDevelopment 72 1091ndash111

Kuroda KO Numan M (2014) The medial preoptic area andthe regulation of parental behavior Neuroscience Bulletin 30863ndash5

Kundakovic M Champagne FA (2015) Early-life experienceepigenetics and the developing brain Neuropsychopharmacology40 141ndash53



Lambert KG Franssen C L Bardi M et al (2011)Characteristic neurobiological patterns differentiate paternalresponsiveness in two Peromyscus species Brain Behavior andEvolution 77 159ndash75

Lancaster JL Tordesillas-Gutierrez D Martinez M et al(2007) Bias between MNI and Talairach coordinates analyzedusing the ICBM-152 brain template Human Brain Mapping 281194ndash205

Leuner B Glasper ER Gould E (2010) Parenting and plasticityTrends in Neurosciences 33 465ndash73

Lovic V Gonzalez A Fleming AS (2001) Maternally separatedrats show deficits in maternal care in adulthood DevelopmentalPsychobiology 39 19ndash33

Ludwig M Leng G (2006) Dendritic peptide release andpeptide-dependent behaviours Nature Reviews Neuroscience 7126ndash36

Meaney MJ (2001) Maternal care gene expression and thetransmission of individual differences in stress reactivityacross generations Annual Review of Neuroscience 24 1161ndash92

Moffitt TE Arseneault L Belsky D et al (2011) A gradient ofchildhood self-control predicts health wealth and publicsafety Proceedings of the National Academy of Science United Statesof America 108 2693ndash8

Molenberghs P Cunnington R Mattingley JB (2012) Brain re-gions with mirror properties a meta-analysis of 125 humanfMRI studies Neuroscience and Biobehavioral Reviews 36 341ndash9

Nguyen HB Bagot RC Diorio J Wong TP Meaney MJ(2015) Maternal care differentially affects neuronal excitabilityand synaptic plasticity in the dorsal and ventral hippocampusNeuropsychopharmacology 40 1590ndash9

Numan M (2012) Maternal behavior neural circuits stimulusvalence and motivational processes Parenting 12 105ndash14

Numan M Young LJ (2016) Neural mechanisms of motherndashinfantbonding and pair bonding similarities differences and broaderimplications Hormones and Behavior 77 98ndash112

Ostfeld-Etzion S Golan O Hirschler-Guttenberg Y Zagoory-Sharon O Feldman R (2015) Neuroendocrine and behavioralresponse to social rupture and repair in preschoolers with aut-ism spectrum disorders interacting with mother and fatherMolecular Autism 6 11

Porges SW (2003) Social engagement and attachment NewYork Academy of Sciences 1008 31ndash47

Posner MI Rothbart MK Sheese BE Voelker P (2014)Developing attention behavioral and brain mechanismsAdvances in Neuroscience 2014 e405094

Rameson LT Morelli SA Lieberman MD (2011) The neuralcorrelates of empathy experience automaticity and prosocialbehavior Journal of Cognitive Neuroscience 24 235ndash45

Raz G Jacob Y Gonen T et al (2014) Cry for her or cry withher context-dependent dissociation of two modes of cine-matic empathy reflected in network cohesion dynamics SocialCognitive and Affective Neuroscience 9 30ndash8

Raz G Winetraub Y Jacob Y et al (2012) Portraying emotionsat their unfolding a multilayered approach for probing dy-namics of neural networks NeuroImage 60 1448ndash61

Riem MME van IJzendoorn MH Tops M Boksem MASRombouts SARB Bakermans-Kranenburg MJ (2012) Nolaughing matter intranasal oxytocin administration changes

functional brain connectivity during exposure to infant laugh-ter Neuropsychopharmacology 37 1257ndash66

Rilling JK DeMarco AC Hackett PD et al (2012) Effects ofintranasal oxytocin and vasopressin on cooperative behaviorand associated brain activity in men Psychoneuroendocrinology37 447ndash61

Rilling JK Young LJ (2014) The biology of mammalian parentingand its effect on offspring social development Science 345 771ndash6

Ross HE Young LJ (2009) Oxytocin and the neural mechan-isms regulating social cognition and affiliative behaviorFrontiers in Neuroendocrinology 30 534ndash47

Royle NJ Russell AF Wilson AJ (2014) The evolution of flex-ible parenting Science 345 776ndash81

Sobel ME (1982) Asymptotic intervals for indirect effects instructural equations models In S Leinhart editor SociologicalMethodology San Francisco Jossey-Bass 290ndash312

Sokolowski K Corbin JG (2012) Wired for behaviors from de-velopment to function of innate limbic system circuitryFrontiers in Molecular Neuroscience 5 7ndash21

Spunt RP Lieberman MD (2013) The busy social brain evi-dence for automaticity and control in the neural systems sup-porting social cognition and action understandingPsychological Science 24 80ndash6

Stanley DA Adolphs R (2013) Toward a neural basis for socialbehavior Neuron 80 816ndash26

Stolzenberg DS Numan M (2011) Hypothalamic interactionwith the mesolimbic DA system in the control of the maternaland sexual behaviors in rats Neuroscience and BiobehavioralReviews 35 826ndash47

Swain JE (2008) Baby stimuli and the parent brain functionalneuroimaging of the neural substrates of parent-infant attach-ment Psychiatry 5 28ndash36

Swain JE (2011a) Becoming a parentmdashbiobehavioral and brainscience perspectives Current Problems in Pediatric andAdolescent Health Care 41 192ndash6

Swain JE (2011b) The human parental brain in vivo neuroi-maging Progress in Neuro-Psychopharmacology and BiologicalPsychiatry 35 1242ndash54

Swain JE Konrath S Brown SL et al (2012) Parenting and be-yond common neurocircuits underlying parental and altruis-tic caregiving Parenting 12 115ndash23

Swain JE Kim P Spicer J et al (2014) Approaching the biol-ogy of human parental attachment brain imaging oxytocinand coordinated assessments of mothers and fathers BrainResearch 1580 78ndash101

Thorndike R Hagen E Sattler J (2003) The Stanford-BinetIntelligence Scale 5th edn Chicago IL Riverside Publication Co

Tinbergen N (1963) On aims and methods of ethologyZeitschrift fur Tierpsychologie 20 410ndash33

van Kerkhof LW Trezza V Mulder T Gao P Voorn PVanderschuren LJ (2013) Cellular activation in limbic brainsystems during social play behaviour in rats Brain Structureand Function 219 1181ndash211

Weaver ICG Cervoni N Champagne FA et al (2004)Epigenetic programming by maternal behavior NatureNeuroscience 7 847ndash54

Wilson EO (2012) On Human Nature Cambridge MA HarvardUniversity Press



physiology and behavior during social contactmdashwhich carriesprofound effects for offspringrsquos adaptation (Kundakovic andChampagne 2015) Plasticity of the parental brain in infancyindicated by increased activations of key brain areas implicatedin mammalian parenting accompanied by structural changes inthe parentrsquos brain initiates the cross-generational sequence ofmammalian sociality (Stolzenberg and Numan 2011 Feldman2015b) Research in rodents has shown that the postpartummarks the period of highest plasticity in the adult brain (Cohenand Mizrahi 2015) when areas of the parentrsquos brain includingthe hypothalamus basolateral amygdala parietal cortex andprefrontal cortex partly triggered by oxytocin (OT) release be-come sensitized to infant cues and initiate the expression ofspecies-typical parental behavior (Featherstone et al 2000Lambert et al 2011) These parenting behaviors in turn organ-ize the infantrsquos brain and behavior toward life within the socialecology (Weaver et al 2004 Numan and Young 2016) Imagingstudies of human parentsrsquo brain show activations in parallelareas in response to infant stimuli similarly associated with OTand the human-specific parenting repertoire (Rilling andYoung 2014 Swain et al 2014 Feldman 2015b Kim et al 2016)Yet the cross-generational sequence of mammalian socialityinitiated by adaptation of the parentrsquos brain in infancy continu-ing with the expression of parenting behavior and culminatingin social adaptation of juveniles has not been tested inhumans Describing such sequence in humans may provide evi-dence that the parentndashinfant interface the junction of evolu-tionary progress marks a unique context where one humanrsquosbrain can profoundly affect another humanrsquos social adaptation

Research on the parental brain described three main net-works underpinning human parenting core limbic embodied-simulationempathy and mentalizing (Rilling and Young 2014Swain et al 2014 Feldman 2015b Kim et al 2016) Studies onthe parental brain in rodents detail the critical role of a core-limbic network including the MPOA of the hypothalamusamygdala and subcortical dopamine reward system Primed byOT surge during parturition and sensitized by sensory stimulifrom infant and nest these structures consolidate into a mam-malian parenting network that subserves parenting (Dulac et al2014 Numan and Young 2015) In humans all imaging studiesof infant visuals show that this highly conserved core-limbicnetwork activates with parentsrsquo exposure to their infantsrsquo pic-tures (Atzil et al 2011 Barrett and Fleming 2011 Swain 2011b2012 Abraham et al 2014 Feldman 2015b) However inhumans the ancient limbic network is connected via multipleascending and descending projections to two main cingulo-insular and fronto-temporo-parietal networks that support theflexibility person-specificity and future-directedness of humanparenting (Swain 2011a Rilling and Young 2014) Theembodied-simulationempathy network consists of structuresin the anterior insular-cingulate cortex that enable the parentto resonate with infant state and emotion ground experience inthe present moment and afford perceptual-motor coupling ofinfant action in the parentrsquos brain via mirror mechanisms(Craig 2009 Gallese 2014) The mentalizing network includingfronto-temporo-parietal structures supports social attributionand theory-of-mind abilities (Spunt and Lieberman 2013) andenables parents to understand infantsrsquo nonverbal communica-tions and infer infant intentions from actions (Frith and Frith2006 2012)

The two cortical networks embodied-simulation and men-talization which jointly comprise the human social brain servemultiple cognitive and associative functions and are superim-posed upon the ancient limbic circuit to create the lsquohuman

parental caregiving networkrsquo that integrates immediate motiv-ational responses with the interoceptive and conscious aspectsof human parenting (Swain 2008 Feldman 2015b Kim et al2015) The complexity of the human parental brain and its inte-gration of primitive with later-evolving structures lend supportto the hypothesis that the cross-generational transfer of humansociality likely combines mammalian-general features withuniquely human brain networks and complex parentndashchild ex-changes to facilitate both survival-related and executive-mental child social outcomes

Developmental studies identified two key competencies thatenable preschool children as they enter the social world to so-cially participate with non-kin adults and peers emotion regu-lation and socialization (Kochanska et al 1995 Eisenberg andMorris 2002) Most crucial is emotion regulation defined as theability to manage states of increased negative or positivearousal to facilitate adaptation or goal-directed activity (Coleet al 2004) Research mainly focused on the regulation of nega-tive emotions addressing the development of emotion regula-tion from simple tactics in infancy to more complex strategiesin preschool that require higher socio-cognitive competenciessuch as executive attention or symbolic communications (Foxand Calkins 2003) Emergence of these complex regulatory abil-ities follows the development of anterior insula and ACC con-nectivity at 3ndash4 years and the increase in Von Economoneurons projection cells found mainly in human cingulo-insular cortex that provide the rapid efficient connectivityneeded for mature self-regulation (Allman et al 2005 Posneret al 2014) Regulation of positive emotions the enhancementand maintenance of positive affect draws on simpler mechan-isms like mimicking or self-soothing which comprise part ofthe infantrsquos self-regulatory repertoire from birth serve an adap-tive survival function and are underpinned by brainstem-limbic system connectivity (Burgdorf and Panksepp 2006)Extant research indicated that emotion-regulation abilities arecritical for social adaptation and that preschoolersrsquo ability toregulate emotions is a stable individual trait that predicts cogni-tive social-emotional life-success and mental-health outcomesthroughout life (Eisenberg et al 2000 Moffitt et al 2011)

The second key ability socialization defined as childrenrsquoswilling compliance with adult commands and internalization ofsocial rules undergoes significant maturation during the pre-school years and similarly predicts long-term social adjust-ment mental health and adult employment (Kochanska et al1995 Daly et al 2015) Importantly although preschoolersrsquo emo-tion regulation and socialization may provide an index of life-time adaptation their roots lie in parentndashinfant synchrony(Feldman 2007b Calkins and Hill 2011) Synchronous inter-actions which build online from the parentrsquos and childrsquos non-verbal signals tune the child to social dialogue and providecritical inputs for organizing the brain basis of intersubjectivitya prerequisite of human social life (Feldman 2007c 2012aGallese 2014)

The central question guiding the current study is whetherand how the human parental brain evolved to facilitate key so-cial abilities in human children as in other mammals We as-sessed parentrsquos brain response to own-infant cues usingfunctional magnetic resonance imaging (fMRI) among primary-caregiving first-time mothers and fathers computed intra- andinter- functional connectivity in the aforementioned three net-works based on parentsrsquo brain response to their own infantmeasured parental OT levels and videotaped parentndashinfantinteractions which were coded offline for parentndashinfant syn-chrony Four years later we revisited families observing









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Documents

Network integrity of the parental brain in infancy ...tive survival function, and are underpinned by brainstem-limbic system connectivity (Burgdorf and Panksepp, 2006). Extant research