Brain Basis in Interaction With Children

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Brain basis of early parent–infant interactions:psychology, physiology, and in vivo functional

neuroimaging studies

James E. Swain, 1 Jeffrey P. Lorberbaum, 2,3 Samet Kose, 3 and Lane Strathearn 4,5

1 Child Study Center, Yale University, New Haven, CT, USA; 2 Psychiatry Department, Penn State University – HersheyMedical Center, Hershey, PA, USA; 3 Brain Stimulation Laboratory, Medical University of South Carolina, Charleston,

SC, USA; 4 Meyer Center for Developmental Pediatrics, Baylor College of Medicine, Houston, TX, USA; 5 HumanNeuroimaging Laboratory, Baylor College of Medicine, Houston, TX, USA

Parenting behavior critically shapes human infants’ current and future behavior. The parent–infantrelationship provides infants with their rst social experiences, forming templates of what they canexpect from others and how to best meet others’ expectations. In this review, we focus on the neuro-biology of parenting behavior, including our own functional magnetic resonance imaging (fMRI) brainimaging experiments of parents. We begin with a discussion of background, perspectives and caveats forconsidering the neurobiology of parent–infant relationships. Then, we discuss aspects of the psychologyof parenting that are signicantly motivating some of the more basic neuroscience research. Followingthat, we discuss some of the neurohormones that are important for the regulation of social bonding, andthe dysregulation of parenting with cocaine abuse. Then, we review the brain circuitry underlyingparenting, proceeding from relevant rodent and nonhuman primate research to human work. Finally,we focus on a study-by-study review of functional neuroimaging studies in humans. Taken together,this research suggests that networks of highly conserved hypothalamic–midbrain–limbic–paralimbic– cortical circuits act in concert to support aspects of parent response to infants, including the emotion,attention, motivation, empathy, decision-making and other thinking that are required to navigate thecomplexities of parenting. Specically, infant stimuli activate basal forebrain regions, which regulatebrain circuits that handle specic nurturing and caregiving responses and activate the brain’s moregeneral circuitry for handling emotions, motivation, attention, and empathy – all of which are crucial foreffective parenting. We argue that an integrated understanding of the brain basis of parenting has

profound implications for mental health. Keywords: Attachment, brain imaging, parent–child inter-action, parent–child relationships, parenting, neuropsychology, neurobiology, neurophysiology, childdevelopment. Abbreviation: fMRI, functional magnetic resonance imaging.

In mammals, species survival critically depends onan extensive repertoire of conserved parental be-havior to sustain each infant through an extensivedependency period and contribute to long-termhealth (Ellison, 2006; Gerhardt, 2006; Leckman &Mayes, 1998; Schore, 2005; Sroufe, 2005). Uni-versal parenting behaviors cross species (Clutton-Brock, 1991) as summarized in Table 1, andinclude pan-cultural human thoughts and activitieslisted in Table 2 (Hrdy, 2000). Such behaviors maybe transmitted genetically or epigenetically (cultur-ally), with the latter permitting the transmission of early life infant experiences across generations,including abusive and neglectful behavior as elab-orated elsewhere in this journal. While we contendthat unifying concepts across species represent auseful starting point to understand the generalscaffolding underlying parental behavior, research-ers are just beginning to link animal studies of parenting with the psychology of human parenting(measured, for example, by interview or videotape

assessment) and the brain circuits that underliecomplex social emotions (measured, for example,by brain imaging of circuits activated by baby sig-nals).

Our working model of the functional neuroana-tomy of parenting behavior begins with rodent datathat point to the importance of basal forebrainstructures (Numan & Insel, 2003). For example,lesions in the vicinity of the medial preoptic area(MPOA) completely abolish all aspects of maternalbehavior. Projections from the MPOA to the midbrainaffect the motivational and approach pathways thatnormally make various pup-directed behaviorsrewarding and also regulate pup retrieval afterseparation. Such pathways involving the MPOA mayin fact regulate a broad range of ritualistic or habit-ual parenting behaviors such as nursing, breast-feeding and nest building through neurocircuitrythat is broadly involved in the appraisal of sensorysalience as well as the internal emotions and cogni-tions that direct attention, set arousal levels, andguide learning and memory to prepare for futurebehaviors. We theorize that normal brain systems,which are initially wired by evolution to handle arange of social behaviors including parenting, go

awry in mental disorders. Many mental disordersmay thus be considered as pathological variants of thoughts and behaviors that are important to par-enting. For example, in addictive disorders, motiva-

Journal of Child Psychology and Psychiatry 48:3/4 (2007), pp 262–287 doi:10.1111/j.1469-7610.2007.01731.x

Ó 2007 The Authors Journal compilation Ó 2007 Association for Child and Adolescent Mental Health.Published by Blackwell Publishing, 9600 Garsington Road, Oxford OX4 2DQ, UK and 350 Main Street, Malden, MA 02148, USA



tional pathways that normally regulate healthy re-sponses to infant stimuli (Panksepp, Nelson, & Siviy,1994) may be hijacked by exogenous substances.Similarly, the systems that cope with the loss of so-cial attachment and short-term grief may be abnor-mally active in depression – a condition that is oftentriggered by social loss (Brockington, 2004; Najib,Lorberbaum, Kose, Bohning, & George, 2004). Thiswould, in turn, interfere with social bonding andparenting itself. Along the same lines, we also spec-ulate that human versions of rodent nest buildingcircuits are co-opted and exaggerated in people withthe hoarding symptoms of obsessive-compulsivedisorder (OCD). Other brain systems that regulatenormal parental preoccupations and rituals may si-milarly malfunction to cause other aspects of anxi-ety, excessive worrying, and OCD (Leckman et al.,1999).

Following this thinking, pediatrician and psycho-analyst Donald Winnicott drew attention to ‘primarymaternal preoccupations’ in 1956. He observed thata mother must experience emotional parentingstates constituting ‘almost an illness’ in order tomeet the physical and psychological needs of herinfant (Winnicott, 1960). In other words, normallyadaptive thoughts and behaviors in the postpartum,such as addiction-like aspects of love, parentalobsessions and hypervigilance for one’s infant’ssafety, may improve infant survival and health, andpromote resiliency, but may malfunction in addictivedisorders and obsessive-compulsive disorder.

In addition, neural systems underlying parent– infant attachment may have substantial overlap withthose underlying other forms of social bonding thatshare an intense, addiction-like concern and focusedattention on a preferred individual, such as withromantic love (Aron et al., 2005; Bartels & Zeki,2004b; Fisher, Aron, Mashek, Li, & Brown, 2002;Hateld & Sprecher, 1986; Jankowiak & Fischer,1992; Leckman et al., 2004; Leckman & Mayes,1999). These systems appear to be sensitive to aseries of important environmental and sensory in-puts that shape the full expression of a parenting or

social bonding type (such epigenetic phenomenaare reviewed elsewhere in this issue). However, whenthe parent–infant bond is disrupted, ranging acrosssituations of mother–infant separation, substance

abuse and maternal depression, or dysregulated asin cases of extreme prematurity, illness or birth de-fects, there may be a feedback that increases riskof disturbed parenting including frank abuseor neglect (Strathearn, Gray, O’Callaghan, &Wood, 2001; Weineld, Sroufe, & Egeland, 2000). In

humans, differences in temperament, as well associoeconomic and environmental factors may alsoimpact the integrity of this mother–infant relation-ship.

As such, measurable differences in early bondinglead to long-standing patterns of thought andbehavior that, in turn, contribute to individual dif-ferences in a person’s risk and resilience proles forpsychopathology in later life, parenting and socialbonding that will impact the next generation.

The psychology of human parent–infantrelationships

From an ethological perspective, parenting is oftenregarded as a subset of caregiving or social behaviorsand thoughts that are evolutionarily conserved, andhave a predictable time course and characteristiccontent (Leckman et al., 2004; Numan & Insel,2003). Competing with each parent’s relationshipwith their infant and motivation to provide parentalcare are the needs of other children or dependants inthe family, occupational duties, the needs of themarital relationship and the demands of the larger

social group. Indeed, parent–infant relationshipshave been considered in many theoretical frame-works. Here we we particularly concencrate onattachment theory, parental motivation, and paren-tal obsessive concern and worry for the welfare of their infants.

Attachment theory and patterns in parent–infant relationships

One of the landmarks of contemporary develop-mental psychology has been its focus on parent– infant attachment (Bowlby, 1969, 1973). In fact, itwas after studying associations between maternaldeprivation and juvenile delinquency that JohnBowlby rst formulated his attachment theory,postulating a universal human need to form closeaffect-laden bonds, primarily between mother andinfant. He also strongly argued, from an evolutionaryperspective, that attachment is an innate biologicalsystem promoting proximity-seeking between aninfant and a specic attachment gure. This prox-imity then increases the likelihood of survival to areproductive age.

Because of this powerful biological instinct,

Bowlby hypothesized that all human infants attachto their caregiver – even if the care is harsh or neg-lectful – but that these latter children manifest dif-ferent patterns of attachment ‘security.’ Infants of

Table 1 Common behavioral elements of maternal care acrossmammalian species

Feature

Nest building and maintenance (place preference)Perceptual exploration (identication of nest and/or offspring)Retrieval (reciprocal calls)

Grooming and kissing or lickingCrouching or preferred nursing positionsNursing and lactation and/or feedingProlonged physical contact/sleeping togetherAggressive behavior in response to perceived threats to their

offspring

Brain basis of early parent–infant interactions 263

Ó 2007 The Authors Journal compilation Ó 2007 Association for Child and Adolescent Mental Health.



caregivers who are available, responsive and sensi-tive to their emotional and physical needs tend tomanifest patterns of ‘secure attachment.’ However, if the care provided is chaotic, unpredictable, rejectingor neglectful, or if the caregiver consistently providesnon-contingent responses to the child, then an

anxious, insecure or disorganized pattern of attach-ment evolves (Shaver, Schwartz, Kirson, & O’Connor,1987). The initial pattern of attachment security wasseen as a developmental pathway of major signi-cance throughout the child’s life course, with longi-tudinal research verifying many of these initialhypotheses (van IJzendoorn, 1995). This under-scores how important one’s early environment is inshaping future behavior.

Over the past decade, a diverse spectrum of re-search has begun to explore the neural basis of attachment – at molecular, cellular and behaviorallevels (Insel & Young, 2001; Strathearn, 2007). Thisresearch has uncovered many parallels betweenBowlby’s original thesis and the biological systemswhich may underlie attachment and stress reactiv-ity. Understanding the neurobiology of attachmentmay thus help in formulating and ameliorating per-vasive and complex social problems such as childabuse and neglect, with relatively simple interven-tions that change one’s early environment. Bowlby’swork has made researchers think how important it isfor contigent loops of interactions to take place be-tween parents and infants in order to ensure survivaland appropriate development. In rodents, in order to

survive, newborns are totally dependent on the ini-tiation of a specic set of maternal behaviors in thepostpartum, such as nest maintenance, pup re-trieval, licking, grooming, arched-back nursing andbold aggression toward infant threats and predators(Leckman & Herman, 2002; MacLean, 1990; Numan& Insel, 2003). These are actually reciprocal beha-viors attuned to the needs of the offspring which areexpressed through a series of behaviors including

vocalizations, nipple-seeking and sucking, and in-fant odors. Such contigent loops of behavior betweenparents and offspring are displayed in Figure 1.Since Bowlby rst published his seminal work onattachment theory, numerous research methodshave been developed to systematically classify

attachment styles, as observed from infancy throughto adulthood. The two most accepted and empiricallytested instruments are the Strange Situation Proce-dure in infancy (Ainsworth & Bell, 1970) and theAdult Attachment Interview (AAI) (Hesse, 1999).Understanding the neurobiological regulation of parental attachment patterns, measured for in-stance by the AAI, may help us understand how at-tachment may be transmitted across generations.

Parenting and xations on joyous love and concernfor infant’s safety

Parents may experience an anxious tension betweenthe joyous reveries of being ‘at one’ with the child,and the intrusive worries that something terriblecould happen and jeopardize the relationship. Theinfant’s moods may reect this, alternating betweenserene contentedness and extreme fussiness. We are just beginning to quantify the frequency and inten-sity of joyfulness and worrying parental preoccupa-tions (Leckman et al., 1999) and how they relate tothe concepts of obsessions and compulsions,addictive disorders and romantic love (Leckmanet al., 2004; Marazziti et al., 2003; Mayes, Swain, &

Leckman, 2005). With regard to the joyful thoughts,many rst-time parents anecdotally are themselvessurprised to report similar feelings such as: ‘No onetold me it was like falling in love.’ Other clear par-enting themes include the tendency to be preoccu-pied with small details of the infant’s appearance,family similarities, and seeing the new infant as‘perfect.’ As one mother said after her baby was born,‘... I just can’t believe it, here she is and she’s so

Figure 1 Model of interdependent relationships between maternal behavior and infant development (Strathearn,2007). Reproduced with permission

264 James E. Swain et al.




perfect, I can’t believe she’s really mine.’ In fact,parents state that the experience of their infant asbeing ‘perfect’ increases during the postpartumperiod, reaching a peak at three months, with 73%and 88% of mothers and fathers endorsing thisexperience, respectively. Future studies may tease

apart the way that happy and anxious preoccupa-tions might interact with each other and betweenparents and infants during bonding (Leckman et al.,1999; Swain, Leckman, Mayes, Feldman, & Schultz,2005). To orient the reader to some aspects of par-ent–infant bonding and associated thoughts andbehaviors, Table 2 lists prominent features of earlyparental love and infant responsiveness. In this ta-ble, ratings (0–4 crosses) are based on the judgmentsof 21 experts on bond-formation and attachment andmean values were rounded to the nearest integer.Using a Wilcoxon signed rank test, parental lovecompared to infant responsiveness was rated asmore focused on checking and things being ‘justright’ for the other, with less aggressive thoughtstoward the other. There were similar ratings in bothparent and infant aspects of parent–infant bondingfor awareness of the other, altered mental state,longing for reciprocity, tendency to idealize the other,emotionally charged reciprocal caring and proximity-seeking behaviors (Leckman et al., 2006).

In early parental love, initial data suggests thatparents frequently feel compelled to shape their ownbehavior to the perceived needs of the baby (Leck-man et al., 1999). Frequently, these behavioral re-

sponses have a ‘just right’ character, such that theyneed to exactly t the apparent needs of the baby.

This heightened sense of responsibility that usuallyaccompanies this state may lead to increased vigil-ance, repeated behaviors aimed at ensuring thesafety of the infant (Leckman et al., 2004) and in-creased sensations of reward.

In the interview studies of parents within the rst

four months postpartum (Leckman et al., 1999;Swain et al., 2004), parents were asked about theoccurrence of specic parenting thoughts and ac-tions for the previous week, such as how preoccupiedthey had been with the baby during the past weekusing a ten-point ordinal scale. Related interviewquestions included requests for time estimates suchas: ‘During the past week, on average how manyhours a day was your mind occupied with thoughtsabout your baby?’ and ‘How long can you go withouthaving thoughts about your child?’ Two of the derivedcontent domains were denoted as Caregiving (CARE),and Anxious Intrusive Thoughts and Harm AvoidantBehaviors (AITHAB or parental preoccupations).CARE was seen as a product of a complex interactionof the parents’ exposure to the infant’s cues(appearance, vocalizations, behavior, soothability),the nature of the current relationship, and the par-ent’s internal working models of their own childhoodattachment gures. The content domain of AITHABwas seen as a heightened sensitivity to potentialthreats (imagined and real) to the well-being of theinfant and repeated behaviors to remove thosethreats. We hypothesized that CARE and AITHABmay be considered to be normal variants of the

mental states and behaviors associated with addict-ive diseases and obsessive-compulsive disorder,

Table 2 Comparison of prominent features of early parent–infant bonding in humans (adapted from Leckman et al., 2006). Earlyparental love was rated by 21 experts as similar to infant responsiveness except where indicted by an asterisk

Feature of love Early parental love Infant responsiveness

Selective recognition – focus exclusivity +++/++++ +++Altered mental state – altered autonomic and behavioral responsivity

conditioned by the absence, presence, or mere cues of the other(s)+++/++++ +++ a

Clear onset – hedonic transformation +++ ++Intrusive thoughts and images (preoccupations):

Longing for reciprocity ++ +++ a

Idealization of the other +++ +++a

Heightened awareness of the other ++++ +++ a

Heightened sense of empathy, responsibility and worries about thewell-being of the other

++++ ++ a

Separation distress ++++ ++++Upsetting aggressive thoughts focused on the self or the other +* +++ a

Altered repetitive behaviors:Proximity seeking and direct physical contact ++++ +++Emotionally charged caring – talking, singing, feeding and grooming ++++ +++Checking to be ensure safety and security, checking that everything

is ‘just right’ ++++* ++

Dichotomous resolution, either:Establishment of intimate mutually satisfying reciprocal patterns of

interaction, usually marked by a culturally dened ritual,reorganization and ongoing development of metacognitive

representations or

+++ +++

Rejection + +

a Initially, the mental processes of the infant are ineffable and likely out of conscious awareness.* p > .01 Wilcoxon Signed Ranks that difference between early parental love and infant responsiveness was signicant.





respectively. In the formulation of the latter, theperformance of compulsive checking behaviors (thateven the parents themselves may regard as excessiveor unnecessary) relieves the intrusive thoughts thatone’s baby has been harmed. Even before the child isborn, parents preoccupy themselves with creating a

safe and secure infant environment. Human nest-building type behaviors are common, includingmajor cleaning and renovation projects in the post-partum. Uppermost among parental concerns andcompulsions are safety (such as excessive infantcleanliness) and unimpeded access to their infant.Preliminary analysis of interview data (Swain et al.,2004) indicates signicantly higher parental preoc-cupations in moms compared to dads ( p < .001), andcorrelations between parental preoccupations anddepression ( p < .001). Later in this article, we willdiscuss the brain systems that underlie parents’ addictive and anxious thoughts and behaviors. In thefuture, studies of how these brain systems malfunc-tion in frankly addictive or obsessive parents mayoffer opportunities for early detection and treatmentoptions in vulnerable individuals.

Certain special cases of parenting bear brief con-sideration. In parental adjustment to the arrival of aninfant, the experience and presence of other childrenin the home are important. Different psychologicaladjustments might be required to maintain close tieswith existing children and the rest of the family, yetthe parents may be more condent and this is partlyreected in the decreased level of parental preoccu-

pation with a second child compared to the rst(Leckman et al., 1999; Swain et al., 2004). Anotherspecial case of becoming a parent that requires dif-ferent adaptations is the example of multiple births.In some cultures, twin births are regarded asunwelcome and unnatural, perhaps due to insuf-cient resources and increased parental preoccupa-tions, and one of the two infants may be killed (Pector,2002). Some parents of twins nd it too difcult toestablish clearly differentiated relationships witheach infant and attempt to merge the twins into asingle unit through similar names, dress, and per-ceived attributes (Robin, Kheroua, & Casati, 1992).In other instances, parents develop clear preferences,clearly favoring one twin more than the other (Mann,1992; Minde, Corter, Goldberg, & Jeffers, 1990). There may be other effects of age and experience toconsider. For example, teen mothers engaged inmore instrumental activities (e.g., changing diapers,adjusting clothes), but less affectionate (e.g., strok-ing, kissing, patting) behavior, and older mothersshowed the opposite, engaging in more affectionateand less instrumental behavior. Further, whengroups were reassessed based on early life experience(consistency of care during the rst 12 years of life, in

which consistent care is having at least one consis-tent caregiver, and inconsistent care is havingmultiple and changing caregivers), an interactionwas also found between consistency of care and type

of behavior shown. Mothers who received inconsis-tent care engaged in more instrumental and lessaffectionate behavior. Also, compared to maturemothers, teen mothers who were breastfeeding alsohad higher salivary cortisol levels, and high cortisolin teen mothers was related to decreased fatigue and

increased energy (Krpan, Coombs, Zinga, Steiner, &Fleming, 2005). Clearly, much more work is requiredto clarify the psychology of the postpartum, theunderlying biology and the implications for infantand family outcomes.

Nursing and feeding are the parental behaviorsthat are perhaps most associated with a new infant.Women describe breastfeeding as a uniquely close,veryphysical, andsometimes sensualexperience thatcreates a particular unity between the mother and herinfant. Cleaning, grooming, play and dressing beha-viors also carry a special valence inasmuch as theypermit the closeness between parent and infant andprovide for frequent inspection of the infant’s bodyand appearance (Leckman et al., 2004).

The presence of xed behavioral patterns in humanparents may at rst seem to be minimal, suppressedor perhaps not as apparent as in rodents. However,detailed videotaped analysis of moment-to-momentparent–infant interaction is prompting a reconsider-ation of the importance of parent–infant behaviors(Feldman, 2003). In addition, special events in familylife are associated ritualistic ceremonies for childnaming, acceptance and guidance into the parents’ social group. We might consider that these social and

parenting behaviors and rituals manifest along acontinuum from adaptive vigilance and habit topathological mood, anxiety and obsessive-compul-sive disorders (Boyer & Lienard, in press; Feygin,Swain, & Leckman, 2006; Swain, in press)

Parenting is regulated by key hormones andneurotransmitters

In addition to far-reaching ‘programming’ of parentsby their own early life experiences, maternal behav-iors are inuenced by current infant cues that acti-vate certain interacting neurotransmitters, includingoxytocin, prolactin, vasopressin and dopamine. Forexample, suckling, audiovisual and olfactory stimulistimulate maternal care in rodents, even modifyingpre-existing behavior patterns (Rosenblatt, 1994;Stern, 1997), at least in part through increasedexpression of oxytocin receptors in specic brainareas (Francis, Champagne, & Meaney, 2000). Incontrast, long periods of mother–infant separationappear to inhibit maternal behavior, through oxyto-cin receptor modulation (Boccia & Pedersen, 2001). The oxytocinergic system is important in the forma-

tion of social and spatial memories, afliative beha-vior and emotion regulation (Ferguson, Young, &Insel, 2002). Oxytocin receptors are enriched in brainareas that are signicant in the manifestation of





social and maternal behavior, including the bed nu-cleus of the stria terminalis, hypothalamic para-ventricular nucleus, central nucleus of the amygdala,ventral tegmental area and lateral septum (Francis,Champagne, & Meaney, 2000). Similar systems aredescribed in nonhuman primates (Winslow, 2005).

Some of the same processes described in animalsthat require oxytocin are also present in the regula-tion of an array of human social behaviors and cog-nitions (Kirsch et al., 2005), including socialreduction of stress (Heinrichs, Baumgartner, Kirs-chbaum, & Ehlert, 2003) and mechanisms of trust(Kosfeld, Heinrichs, Zak, Fischbacher, & Fehr, 2005;Zak, Kurzban, & Matzner, 2004). Oxytocin releasedin mothers during breastfeeding is also associatedwith reduced levels of maternal anxiety and atte-nuated physiological stress response (Chiodera &Coiro, 1987; Legros, Chiodera, & Geenen, 1988), andmore attuned patterns of maternal behavior acrossspecies (Champagne & Meaney, 2001; Uvnas-Moberg, 1998; Uvnas-Moberg & Eriksson, 1996).Perhaps among the many complex aspects of breastfeeding, oxytocin in the mother may play a rolein transmitting infant cues to mothers and en-couraging other parenting behaviors. This notion isconsistent with the observation that the stress of prolonged mother–infant separation in humans isassociated with reduced maternal sensitivity, andmore negative patterns of mothering throughout therst 3 years of life (NICHD, 1999). In addition tofurther supporting the importance of oxytocin for

maternal behaviors, rodent gene knockout studieshave conrmed the importance of prolactin, estro-gen, and dopamine (Leckman & Herman, 2002).

Besides broad roles in motivation and rewardsystems (Schultz, 2006), dopamine directly mod-ulates oxytocinergic systems in the female prairievole nucleus accumbens that are critical for theformation of social attachment (Liu & Wang, 2003;Young, Murphy Young, & Hammock, 2005). Wewould predict that neuroimaging studies of hypo-oxytocinergic non-breastfeeding mothers as well asnon-parents will show decreased responses to par-enting in areas that have oxytocin receptors or directconnections to oxytocin-sensitive areas. Under-standing the links between healthy parenting andthe normal modulation of anxiety, motivation andreward as well as the aberrations in these systemsthat may be associated with neglect or abuse willhelp us better prevent and treat these issues. Aber-rant situations, in which cocaine abuse or mooddisorders might hijack motivation and reward cir-cuits and interfere with social bonding, is the subjectof current research efforts and discussed in thefollowing sections below.

Cocaine and maternal behavior

Maternal cocaine abuse is a signicant public healthissue, particularly affecting children with high rates

of abuse, neglect, foster care placement (Chafn,Kelleher, & Hollenberg, 1996) and disturbed at-tachment (Seifer et al., 2004). An estimated 4.6million women use cocaine each year in the UnitedStates, with 750,000 drug-exposed births occurringannually (Porter & Porter, 2004). However, we know

little about how cocaine exposure affects brain cir-cuits involved in maternal behavior, especially inhumans.

The neuropeptide hormone, oxytocin, already dis-cussed above in normal parenting, may be affectedby cocaine exposure (Johns et al., 2005a, 2005b).One human study demonstrated signicant differ-ences in peripheral oxytocin responses between co-caine exposed mothers and matched controls, inresponse to infant contact and a stressor (Lightet al., 2004). Thus, natural infant-related rewardstimuli and articial stimulants such as cocaine maydifferentially affect neural development, throughboth dopamine and oxytocin.

For most mothers, interacting and engaging withone’s own infant is a rewarding and pleasurableexperience that promotes mother–infant attachment,ensures optimal care for the developing infant, andmotivates maternal behavior, even in the face of ex-treme fatigue and competing needs for attention.However, animal and human research suggests thatcocaine-exposed mothers, even when not activelyusing the drug, may be less able to respond appro-priately to their infants’ cues, or may nd theseinteractions less intrinsically rewarding. Thus, co-

caine effectively appropriates the motivation circuitsthat normally regulate parenting, resulting in in-creased risk of infant neglect or even abuse. In turn,many cases result in court ordered separation of mother and baby and intensication of trauma toboth.

In mothers previously exposed to cocaine, a rangeof important, though sometimes subtle, abnormal-ities in maternal caregiving behaviors have also beennoted, such as mothers being less attentive andmore interrupting of dyadic exchanges (LaGasseet al., 2003; Mayes, Bornstein, Chawarska, &Granger, 1995; Mayes, Granger, Frank, Schotten-feld, & Bornstein, 1993; Tronick et al., 2005). Ani-mal models support the hypothesis that maternalcocaine exposure affects dopaminergic brain path-ways, which, in turn, affects early postpartummaternal care (Johns et al., 2005b). However, poss-ible confounding inuences include the mother’sown adverse childhood experience, which may alsoresult in differences in maternal behavior (Francis,Diorio, Liu, & Meaney, 1999) and predispose tosubstance abuse (Kosten, Zhang, & Kehoe, 2006).

We conjecture that cocaine exposure and adversechildhood experience inuence maternal responses

to infant cues, perhaps interactively, as a resultof neurobiological changes in mesocorticolimbic re-gions of the brain, and altered reward perception andsalience. We also suspect that these changes may





result from variations in gene expression. A recentfMRI animal study demonstrated that cocaine ex-posure prior to pregnancy resulted in a signicantlyreduced brain response to pup suckling, in themedial prefrontal cortex, associated with reduceddopamine production (Febo, Numan, & Ferris, 2005;

Ferris et al., 2005). Another study showed that lowlevels of maternal care were associated with reduceddopamine release in the nucleus accumbens, in re-sponse to pup cues (Champagne et al., 2004). Asdiscussed previously, cross-fostering studies in ratsstrongly suggest that maternal care received in in-fancy is causally related to subsequent maternalbehavior in adulthood (Francis & Meaney, 1999;Pedersen & Boccia, 2002). Thus, maternal care ininfancy may enhance the development of dopami-nergic reward pathways, resulting in enhancedcapacity of offspring to later provide maternal care.

Indeed, human and animal fMRI studies haveshown that cocaine activates both the mesocortico-limbic and the nigrostriatal dopamine systems(Breiter et al., 1997; Kufahl et al., 2005). In lactatingrats, pup suckling produces a remarkably similarpattern of brain activation, including reward-asso-ciated brain regions (Ferris et al., 2005). Studies of human mothers have demonstrated that infant cues,such as facial expressions and cries, activate similarbrain reward regions to cocaine, including the vent-ral tegmental area/substantia nigra region, nucleusaccumbens, cingulate and prefrontal cortices. Thus,in non-drug-addicted mothers, exposure to infant

cues appears to be highly reinforcing (or at least in-vokes motivation to respond and approach behavioras in infant crying), and important in activatinghealthy maternal reward and motivational circuits.Healthy parent–infant interactions, which maythemselves be addiction-like (Insel, 2003), are dis-rupted by articial stimulants of the dopaminergicsystem, such as cocaine which may act as a highlyreinforcing infant substitute (Meaney, Brake, &Gratton, 2002).

Parental behavior disturbances in postpartum

depressionIn addition to understanding normal human par-enting in order to optimize health outcomes, re-search on parents who suffer mental healthproblems such as substance abuse (discussedabove) and mood disorders promises to improve re-cognition, treatment and prevention of disturbedparenting.

Recently published follow-up data on the offspringof depressed and anxious mothers indicating in-creased mental health risks (Brown, Bifulco, &Harris, 1987; Heim, Owens, Plotsky, & Nemeroff,

1997; Kendler, Kessler, Neale, Heath, & Eaves,1993; Sroufe, Carlson, Levy, & Egeland, 1999) un-derscores the signicance of work in this area.Clearly, parental wellness (and/or the presence of

other attuned caregiving adults) has long-term po-sitive effects on resiliency and emotional well-beingof children as they grow up and for decades later.Indeed, longitudinal studies of high-risk infantssuggest that secure attachment in the perinatalperiod is associated with a degree of resiliency and

protection against the development of psycho-pathology later in life (Werner, 2004).Parental mental health problems in the post-

partum, such as depression and anxiety, are com-mon and contribute signicantly to parent–infantattachment problems. Postpartum depression fol-lows 10% to 15% of all deliveries (Caplan et al.,1989) and more than 60% of patients have an onsetof symptoms within the rst 6 weeks postpartum(Stowe & Nemeroff, 1995). While more commonthan problems such as pre-term delivery, post-partum depression and anxiety have received muchless investigative attention and not a single fMRIstudy (Squire & Stein, 2003). A growing body of evidence from naturalistic longitudinal studies at-tests to an adverse impact of postpartum depres-sion, with depressed mothers less sensitivelyattuned to their infants, less afrming and morenegative in describing their infant. These dis-turbances in early mother–infant interactions werefound to predict poorer infant cognitive outcome at18 months (Murray & Cooper, 2003) and later time-points such as 7 years (Kim-Cohen, Moftt, Taylor,Pawlby, & Caspi, 2005).

However, a recent study showed that maternal

remission from depression within 3 months wasassociated with signicant decreases in the moodsymptoms of their children, who were 7–17 years of age (Weissman et al., 2006). We would predict aneven more dramatic effect in younger children. Inefforts to understand the underlying physiology,brain imaging studies are currently under way(Mayes, Swain, & Leckman, 2005) with parents atrisk for postpartum depression. We predict thatsuch work will outline future opportunities toidentify families at risk for pathological attachment,assess treatments and improve parent–childattachment.

Neuroanatomical circuits of parenting

Understanding of the underlying neuroanatomy isnecessary for interpreting the interplay of differentneurotransmitters in health and illness. Animalmodels of parental behavior highlight the importanceof specic brain circuits that regulate parenting perse as well general aspects of reward, motivation,sensory processing and approach vs. avoidancedecision making. Please refer to Figure 2, indicating

the regions that we expect to be critical to humanparenting, extrapolated from work on rodent behav-iors (Table 1) that we summarize below as a preludeto the human imaging studies.





Maternal behavior regulation by motivational systems of the basal forebrain and midbrain

In the rat, the structures showing the most convin-cing evidence for a central role in maternal behaviorare the medial preoptic area (MPOA) and nearbyventral part of the bed nucleus of the stria terminalis(VBNST) (Numan, 1994). These are small basalforebrain structures lying just anterior to the optic

chiasm and hormone regulatory systems of thehypothalamus. Lesions of the MPOA/VBNST regionor its lateral efferent connections clearly disruptmaternal behavior (Numan, 1974; Numan, Corodi-mas, Numan, Factor, & Piers, 1988; Numan,McSparren, & Numan, 1990; Numan, Morrell, &Pfaff, 1985; Numan & Numan, 1996) and estradiolinjections into the MPOA/VBNST facilitate maternalbehavior (Numan, Rosenblatt, & Komisaruk, 1977).MPOA/VBNST outputs include posterior projectionsto the hypothalamus and midbrain regions such asthe ventral tegmental area (VTA) and retrorubralelds/substantia nigra which are rich in dopamineand important in motivated approach behavior(Mirenowicz & Schultz, 1996). Such behavior may berequired in pup retrieval, motivation to care forpups, and foraging (Numan, Morrell, & Pfaff, 1985;Numan & Nagle, 1983). The VTA and substantia ni-gra project along the mesolimbic, mesocortical, ornigrostriatal dopaminergic pathways (midbrain– striatal–anterior cingulate/prefrontal cortex regions)(Mello & Villares, 1997), and lesions along thesepathways also interfere with maternal behavior(Numan & Numan, 1997). For example, ventralstriatal/nucleus accumbens lesions impair maternal

behavior (Hansen, 1994), and infant cues appear totrigger dopamine release in the nucleus accumbens(Champagne et al., 2004). There are also indicationsthat other midbrain sites are potentially important in

maternal behavior. For example, MPOA projectionsto the peripeduncular nuclei in the lateral midbrain’sretrorubral eld region may be involved in a mother’smilk letdown response (Factor, Mayer, & Rosenblatt,1993; Hansen & Kohler, 1984). The function of theMPOA projections to the midbrain’s central gray

matter, a region known to be involved in defensivebehavior, is not well known. However, such projec-tions could be potentially important for maternalaggressiveness toward intruders (Lonstein, Sim-mons, Swann, & Stern, 1998; Lonstein & Stern,1997), preventing a mother’s aggression towardpups (Numan & Sheehan, 1997), or even a mother’sassuming the correct kyphotic nursing posture(Lonstein, Simmons, Swann, & Stern, 1998; Lon-stein & Stern, 1997; Numan & Numan, 1997).

Maternal behavior regulation by emotion control

circuits involving the amygdala and septal regionsLimbic regions such as the amygdala and the septalregion also connect to the MPOA and are thought tobe important for parenting. For example, the amyg-dala may mediate the avoidance of young pup smellsby nulliparous rat females (Numan & Sheehan,1997), since it is also known to mediate the aversiveresponses to foul odors (LeDoux, 1996). The hor-monal changes of pregnancy might convert pupsmells from an aversive to a non-aversive or perhapseven rewarding odor. Female nulliparous rats whoare made anosmic (Fleming, Vaccarino, Tambosso, &

Chee, 1979), undergo the hormonal changes of pregnancy (Numan, 1994), or have amygdala lesions(Fleming, Miceli, & Moretto, 1983; Numan, Numan,& English, 1993), no longer avoid pups and mayeven exhibit maternal behavior. These data indicatethat the amygdala may inhibit maternal behavior inthe rat through the olfactory system. In contrast, theamygdala has also been reported to play a role infacilitating maternal behavior in nonhuman pri-mates (Kling & Steklis, 1976). These opposing nd-ings may be explained by studies of sub-regions of the amygdala. In one such study, different regions of the central amygdala have been shown to containtwo distinct neuronal populations, through whichoxytocin modulates the integration of excitatoryinformation from the basolateral amygdala and cer-ebral cortex in opposite manners (Huber, Veinante,& Stoop, 2005). Thus, different populations of cellsin a small structure such as the amygdala may infact exert opposing effects on the autonomic nervoussystem and parenting behavior.

The septal region of the brain may also be im-portant in nest building, orchestrating pup retrieval,and controlling aggression toward pups (Numan &Numan, 1997). For example, nest building in mice is

arrested by septal lesions (Slotnick & Nigrosh, 1975),and rodents with septal lesions are also more proneto commit infanticide (Flannelly, Kemble, Blanchard,& Blanchard, 1986; Novakova, Sterc, Kuchar, &

Thalamus

Cingulate SeptalRegion

MedialPreoptic AreaHypothalamus

Midbrain

Figure 2 Human parental brain areas. Brain regionsexpected to be important to human parenting, based on

animal studies of mother–infant behaviors. The stria-tum and amygdala are not shown





Mozes, 1993; Slotnick & Nigrosh, 1975). Moreover,in mice with septal lesions, pup retrieval becomesdisorganized (Slotnick & Nigrosh, 1975) such thatmothers with septal lesions often drop them andleave them scattered around the cage rather than inthe nest.

Maternal behavior regulation by sensation driventhalamocingulate circuits

Several animal studies suggest that the cingulategyrus and its connected thalamic nuclei (such asdorsomedial, medial pulvinar, midline, and anterior)also play a pivotal role in mammalian maternalbehavior (Mesulam, 2000). These structures regulateselective attention through dopamine approachpathways. Cingulate lesions, which in turn causeretrograde degeneration of medial thalamic nuclei,impair maternal behavior in rats and hamsters(MacLean, 1990; Murphy, MacLean, & Hamilton,1981; Slotnick, 1967; Stamm, 1955). For example,rat and hamster mothers with cingulate lesions(which may include the neighboring midline cortex)often have problems nest building, retrieving pupswhen separated, actively allowing their pups tonurse, and sustaining pups through weaning (Mac-Lean, 1990; Murphy, MacLean, & Hamilton, 1981;Slotnick, 1967; Stamm, 1955). In fact, the degree of maternal behavior impairment appears to stronglycorrelate with the degree of accompanying anteriorthalamic nuclei degeneration (Slotnick, 1967; Slot-

nick & Nigrosh, 1975). Further, motivation to carefor pups appears to be present but motheringbehaviors seem disorganized in a manner that issimilar to that produced by septal lesions. Also,electrical stimulation of the anterior cingulate infemale rabbits (Aulsebrook & Holland, 1969) cancause oxytocin release, milk ejection, and uterinecontractions (Slotnick, 1967; Stamm, 1955). Evenmore evidence for the cingulate’s involvement inmaternal behavior is that the anterior cingulatecortex is rich in opiate receptors (Wise & Herken-ham, 1982). In several species, opiates inuencematernal retrieval of separated young (Panksepp,Nelson, & Siviy, 1994). On the other hand, somehave failed to nd altered maternal behavior withcingulate lesions in mice (Slotnick & Nigrosh, 1975);and in the rat, maternal behavior is associated withprominent c-fos labeling in the basal forebrain, butnot the cingulate cortex (Lonstein, Simmons, Swann,& Stern, 1998). Thus, it could be that the cingulate isimportant to organize a range of complex behaviortypes, of which parenting is one.

Integrative physiology of normal parentingbehaviors

While most of the pioneering and systematic work onmaternal brain behavior has been performed with

rodents, there is a growing body of converging workon the human brain basis of parenting. Given ourshared mammalian evolutionary heritage, it makessense that some of the same bioactive chemicals andstructures mediate parenting and social bondingthrough similar mechanisms across species. For

example, human afliative behaviors have beenconsidered as part of an elaborate reward and stress-sensitive system that requires dopamine and oxyto-cin, and a host of other neurotransmitters includingopiates as well as pituitary and gonadal hormones. Ithas been proposed that this system can be simpliedas domains of sensation, perception, attention,learning and memory (Depue & Morrone-Strupinsky,2005).

Altered activity of the dopaminergic system hasalso been associated with a wide range of humandiseases and psychopathology. These include drugaddiction, attention decit hyperactivity disorder,obesity, compulsive gambling, and several person-ality traits (Blum et al., 2000; Comings & Blum,2000) – arguably all of which involve malfunctioningmotivation systems. We suggest that all of these maybe associated with adverse early life events. A recentPET study showed that dopamine production in thehuman brain was associated with reduced self-reported maternal care in childhood (Pruessner,Champagne, Meaney, & Dagher, 2004). Abnormaldevelopment of the dopaminergic system may also beassociated with differing patterns of adult attach-ment, with a relative decit seen in ‘preoccupied’

patterns and an excess in ‘dismissing’ types. Thishypothesis is currently being explored using fMRI toexplore patterns of parental brain response accord-ing to attachment classication (Strathearn, 2007).

As for oxytocin, receptor binding sites measured atautopsy in humans appear in many of the regionspreviously mentioned as potentially important to ratmaternal behavior. These include the preoptic area/hypothalamus region, midbrain and upper ponssites (especially the substantia nigra, central grayregions, and superior colliculus), and lateral septalarea (Loup, Tribollet, Dubois-Dauphin, & Dreifuss,1991; Loup, Tribollet, Dubois-Dauphin, Pizzolato, &Dreifuss, 1989). There are also human oxytocinbinding sites in other brain regions including thebasal nucleus of Meynert, diagonal band of Broca,and lower pons/medulla/upper spinal cord sites(facial nucleus, nucleus of the solitary tract, spinaltrigeminal nucleus, rostral nucleus ambiguus,hypoglossal nucleus, area postrema, and dorsalhorn of the upper spinal cord) suggesting an ex-tended range of functions.

Evidence for the importance of stress hormones inparenting includes the work of Fleming and co-workers (Fleming, Steiner, & Corter, 1997), who

found that rst-time mothers with high levels of circulating cortisol were better able to identifytheir own infant’s odors. In these same primip-arous mothers, the level of affectionate infant





contact (affectionate burping, stroking, poking andhugging) by the mother was related to levels of salivary cortisol.

A key question for research on human parenting iswhich infant stimuli elicit parental thoughts andfeelings most potently and meaningfully. MacLean

(1990), a pioneer in neuroethological approaches tobrain research, hypothesized that the brain’s thal-amocingulate division (the cingulate cortex and itsconnected medially located thalamic nuclei) isimportant in mammalian mother–infant attachmentbehavior such as infant crying (a caretaking elicitorin all studied mammals) and a mother’s caretakingresponse. MacLean (1990) reasoned that the thal-amocingulate division is likely involved in parentingbehavior and attachment behavior, since it is pre-sent in mammals but not in lizard-like reptiles, who,unlike mammals, do not cry, exhibit signicantparental care, or even hear well. In fact, lizard-likereptiles are likely to eat their young if they nd them.Alligators and crocodiles that provide some maternalcare are more evolutionarily related to birds anddinosaurs and have a rudimentary anterior cingu-late. Further, lesioning the thalamocortical circuitappears to impair executive control of maternal be-havior and produces disorganized pup retrieval, ra-ther than a lack of motivation to respond. MacLean’sevolutionary theories have been a major inspirationin our eld, including insights about the importanceof the universally present mammalian caretakingcue of infant vocalizations.

Thus far, however, there is not strong evidence foracoustically distinct infant cry types in humans, inthe way that hunger and separation cries have beenfound in animals (Newman, 2003). It has been sug-gested that human infant cries may function and becharacterized rather as graded signals (Soltis, 2004).During pain-induced autonomic nervous systemarousal, for example, neural input to the vocal cordsincreases cry pitch in a graded fashion. Caregiversmay use this acoustic information, together withother cues, to guide caregiving behavior. In onestudy of normal parents, controlled for extraneouscues, 80% of mothers were able to recognize theirinfants’ cries, as were 45% of fathers at 30 dayspostpartum (Green & Gustafson, 1983). Seriouspathology, on the other hand, results in chronicallyand severely abnormal cry acoustics. Such abnormalcrying may be a proximate cause of infant mal-treatment in circumstances in which parents reduceor withdraw investment from infants with low sur-vival chances. An increase in the amount of cryingduring the rst few months of life is universal inhumans, and excessive crying, or colic, representsthe upper end of this normal increase. Potentialsignal functions of excessive crying include mani-

pulation of parents to acquire additional resources,honest signaling of need, and honest signaling of vigor (Soltis, 2004). Manipulation in the context of infant behavior refers to signaling for more resources

than might be necessary for survival. Infant cry–careloops may thus be thought of as part of an elaborate,dynamic and interactive communication system thatmaintains proximity to and elicits care from care-givers (MacLean, 1990; Swain, Mayes, & Leckman,2004).

Fathers have also been studied for physiologicalmarkers of parenting. In one set of studies, Flemingand colleagues found that fathers hearing baby crystimuli felt more sympathetic and more alert com-pared to groups who did not hear the cries or to non-fathers who heard the cries, and testosterone andprolactin were key mediators of paternal physiology.Fathers and non-fathers with lower testosterone le-vels had higher sympathy and/or need to respond tothe infant cries than fathers with higher testosteronelevels. In addition, fathers hearing the cry stimulishowed a greater percentage increase in testosteronethan fathers not hearing the cry stimuli, and bothexperience and testosterone contributed to the var-iance in fathers’ affective responses to infant cries.Prolactin levels were higher with paternal alertnessand positive response to the cries, and experiencedfathers hearing the cries showed a greater percent-age increase in prolactin levels compared to rst-time fathers or to any group of fathers hearingcontrol stimuli (Fleming, Corter, Stallings, & Steiner,2002). These results are particularly interesting inlight of the convergent ndings that men and womenhave similar stage-specic differences in hormonelevels, including higher concentrations of prolactin

and cortisol in the period just before the births andlower postnatal concentrations of sex steroids (tes-tosterone or estradiol). Men with more pregnancysymptoms (couvade) and men who were most affec-ted by the infant reactivity test had higher prolactinlevels and greater post-test reduction in testoster-one. Hormone concentrations were correlatedbetween partners. This pattern of hormonal changein men and other, paternal mammals, and itsabsence in nonpaternal species, suggests thatcertain hormones also play key roles in primingmales to provide care for their young (Storey, Walsh,Quinton, & Wynne-Edwards, 2000).

Another potentially important maternal behaviorconcerns the infant carrying hypothesis (Salk, 1960),which is based on the observation that most women(whether they were right- or left-handed) carry theirinfants with their left arm so that the infant’s headlies against the left breast. Many higher primatesappear to do so as well (Sieratzki & Woll, 1996).While it could be true that a major evolutionary forceguiding the left-sided infant carrying might be thatthis places the infant near the mother’s heartbeat, animportant effect of placing a child on the left is thatthe infant lies in the mother’s left visual eld with

more direct communication to the right hemisphere(Sieratzki & Woll, 1996). Some have taken this tomean that the right cerebral cortex may have a spe-cialized role in human social attachment (Henry,





1993; Horton, 1995; MacLean, 1990; Sieratzki &Woll, 1996). Horton (1995) tested whether the righthemisphere is involved in ‘giving others comfort’, byoffering men and women a choice of helping one of two identical teddy bears, one on the right and theother on the left. Each bear was said to be in distress

and in urgent need of help. People more often choseto comfort the teddy bear on their left with mothersmore so than non-mothers and men. This result wasmore pronounced among females, especially moth-ers (Horton, 1995). This was not true for picking up aball which most people pick up on the right side tothrow. Consistent with this are observations of pre-dominantly right-sided brain response in early brainimaging experiments described below.

Brain imaging of human parent–infant

relationshipsIn this section, we present data on the brain basis of human maternal behavior and thoughts, using thehigh resolution and non-invasive technique of fMRI. This is a brain imaging technique which assays brainactivity by measuring blood oxygenation. The differ-ences between oxygenated and deoxygenated hemo-globin provide characteristic magnetic signals thatare detected by scanners positioned around the headof each subject, and the signals are localized tomillimeter resolution. An important caveat through-out the interpretation fMRI studies is that that brain

activity measurements represent an integration of activity over blocks of several seconds. In thesestudies, auditory and visual baby and control stimuliare presented to parents during these blocks. Brainactivity may then be measured and compared be-tween periods of attending to different stimuli togenerate maps of the brain indicating differences inbrain activity that may be important for one set of thoughts versus another. For example, comparisonof brain activity during baby cry vs. control noiseexperience may yield signicant differences in cer-tain brain regions that may then be said to relate tothe experience of a baby cry, and so the associatedparenting thoughts and behaviors. The experimentsto date using baby sound and visual stimuli withbrain fMRI are summarized in Tables 3 and 4respectively. These inclusive reference tables areintended to suggest patterns of response across allstudies and stimuli at a glance, to provide a roughmodel of the brain areas important for human par-enting and to stimulate future studies. Parent brainareas of increased activity with baby stimuli areindicated in these tables with ‘ACT’ and a goldbackground, while areas of decreased activity areindicated by ‘DEACT’ and a blue background. Also

indicated are the number of subjects, age of infantsat time of scan, type of study (magnet strength andblock or event design), and stimuli used in eachstudy. Statistical methods vary across studies, but

all ndings satisfy the criteria of xed effects at p < .001, or random effects at p < .05. Each of thesestudies along with closely related research is detailedin the following sections after a brief orientation toparenting brain circuits.

First, based on animal studies of parenting

behaviors in animals reviewed in previous sections,we expect that human parenting brain responses willinclude motivation circuits of the midbrain and basalforebrain, emotion control circuits involving theamygdala and other limbic regions and sensationdriven emotion and decision-making thalamocingu-late circuits (Figure 2). In humans, we would alsoexpect that regions involved in the appraisal of par-enting context and memory would require hippo-campal and parahippocampal circuits. Finally, wesuppose that higher order emotion and cognitionareas facilitate parental empathy and caregiving forthe infant, especially in humans. Empathy in generalrequires forming a model of another’s mind thatpredicts their behavior and inuences emotions(Baron-Cohen & Wheelwright, 2004). Parentalempathy toward an infant would require the under-standing and predicting of one’s infant’s mentalstates and behaviors as well as the experiencing of appropriate emotions. Candidate brain circuits thatcould support parental empathy include a variety of cortical regions including inferior frontal, premotor,insular, temporo-parietal and cingulate cortices(Decety & Grezes, 2006; Saxe, 2006a).

In order to explicitly study the biological bases of

human attachment, brain activity can be measuredduring tasks designed to activate the underlyingsystems. An example of this innovative approachused the projective measure of broad aspects of adultattachment (the adult attachment projective) duringbrain scanning (Buchheim et al., 2006). In this pilotstudy of eleven women, line drawings meant to acti-vate the attachment system (illness, solitude, separ-ation and abuse) were presented to subjects duringbrain imaging. The authors reported that subjectswith organized compared to disorganized attachmentpatterns showed increased activity in the right amy-gdala, left hippocampus and right inferior frontalgyrus – areas hypothesized to be important in theattachment system. Allied research on the brainbasis of thinking about other minds (mentalization) isalso beginning to dissect the brain basis of complexsocial emotional thinking (Pelphrey, Morris, Michel-ich, Allison, & McCarthy, 2005; Saxe, 2006b), andthis research suggests that specic regions in themedial prefrontal cortex and temporal cortex mediateaspects of emotional empathy and collaborativebehaviors. In the following section, we describeattempts to specically understand the brain basis of parental attachment by presenting emotionally

charged infant stimuli during brain imaging. Wehypothesize that ‘parenting’ brain circuits, which areactivated by baby stimuli, share much with circuitsthat regulate other social attachments, and might be





T a b l e 3 H u m a n p a r e n t b r a i n r e s p o n s e s t o i n f a n t c r i e s . A n a t o m i c a l b r a i n r e g i o n s w i t h

i n c r e a s e d a c t i v i t y ( A C T ) d u r i n g i n f a n t

c r y a r e i n d i c a t e d i n g o l d , a n d a r e a s o f d e c r e a s e d a c t i v i t y

( D E A C T ) a r e i n d i c a t e d i n b l u e . E m p t y b o x e s i n d i c a t e n o s i g n i c a n t c h a n g e s i n b r a i n a c t i v i t y w i t h e x p o s u r e t o b a b y s o u n d s

A u t h o r ( y e a r ) :

L o r b e r b a u m e t a l .

( 1 9 9 9 )

L o r b e r b a u m e t a l .

( 2 0 0 2 )

S e i f r i t z e t a l .

( 2 0 0 3 )

S w a i n e t a l .

( 2 0 0 3 , 2 0 0 4 )

S w a i n e t a l .

( 2 0 0 3 , 2 0 0 4 )

N u m b e r o f

s u b j e c t s :

n ¼

4

n ¼

1 0

n ¼

2 0

n ¼

7 – 1 4

n ¼

7 – 8

A g e o f i n f a n t s a t t i m e o f s c a n :

3 w e e k s –

3 . 5 y e a r s

1 – 2 m o n t h s

< 3 y e a r s

t i m e 1 : 2 – 4 w e e k s , t i m e

2 : 3 – 4 m o n t h s

t i m e 1 : 2 – 4 w e e k s , t i m e

2 : 3 – 4 m o n t h s

P a r e n t a l g r o u p s :

m o t h e r s o n l y


m o t h e r s + f a t h e r s +

n o n - p a r e n

t s

n o v i c e + m u l t i p a r o u s

m o t h e r s


f a t h e r s

T y p e o f s t u d y :

1 . 5 T , 3 0

s b l o c k s ,

x e d e f f e c t s

1 . 5 T , 3 0 s b l o c k s

r a n d o m e f f e c t s

1 . 5 T , 6 s e v e n t s


3 T , 3 0 s b l o c k s x e d

e f f e c t s

3 T , 3 0 s b l o c k s x e d

e f f e c t s

B a b y c r y u s e d :

o t h e r c r y > w h i t e

n o i s e

o t h e r c r y > c o n t r o l

n o i s e

o t h e r c r y + l a u g h

o w n c r y

> c o n t r o l

o t h e r c r y

> c o n t r o l

o w n c r y

> c o n t r o l

o t h e r c r y

> c o n t r o l

S e p t a l r e g i o n s ( M P O A / V B N S T /

c a u d a t e h e a d )

A C T

A C T

A C T

H y p o t h a l a m u s

A C T

A C T

A C T

T h a l a m u s

A C T

A C T

A C T

S t r i a t u m / P u t a m e n / N u c l e u s

a c c u m b e n s

A C T

A C T

A C T

A C T

A n t e r i o r c i n g u l a t e

A C T

A C T

D E A C T

A C T

A C T

A C T

A C T

M i d d l e c i n g u l a t e

A C T

A C T

P o s t e r i o r c i n g u l a t e

A C T

A m y g d a l a

A C T ( c r y - r e s t

)

A C T

A C T

L e n t i f o r m n u c l e u s G l o b u s p a l l i d u s

A C T

A C T

A C T

H i p p o c a m p u s

A C T

A C T

M i d b r a i n

A C T

A C T

A C T

A C T

I n s u l a

A C T

A C T

A C T

A C T

A C T

O r b i t o f r o n t a l / I n f e r i o r f r o n t a l g y r i

A C T

A C T

A C T

A C T

A C T

M e d i a l f r o n t a l G y r u s

A C T

A C T

D E A C T

D E A C T

A C T

V e n t r a l p r e f r o n t a l c o r t e x

A C T

A C T

T e m p o r o p a r i e t a l c o r t e x

A C T

A C T

A C T

A C T

A C T

A C T

P a r a h i p p o c a m a l / L i m b i c l o b e

A C T

A C T

O c c i p i t a l c o r t e x

N o t e x a m i n e d


A C T

A C T

A C T

F u s i f o r m g y r u s

A C T

A C T

A C T

A C T

T e m p o r a l / A u d i t o r y c o r t e x

A C T

A C T

A C T

C e r e b e l l u m



A C T

A C T

A C T

G l o s s a r y f o r T a b l e s 3 a n d 4 : A c t i v a t i o n s a n d d e a c t i v a t i o n s , m e a s u r e d b y f u n c t i o n a l m a g n e t i c r e s o n a n c e i m a g i n g , s a t i s e d s i g n i c a n c e c r i t e r i a o f r a n d o m e f f e c t s a n a l y s i s a t p < . 0 5

o r x e d

e f f e c t s a n a l y s i s a t p < . 0 0 1

a t a m i n i m u m ; T ¼

T e s l a ( u n i t o f m a g n e t i c e l d s t r e n g t h ) ; b l o c k s ¼ p e r i o d s o f s t i m u l u s e x p o s u r e a n d f M R I d a t a a c q u i s i t i o n ; e v e n t s ¼

b r i e f e x p o s u r e s t o i n f a n t

s t i m u l i d u r i n g f M R I e x p e r i m e n t s ; o t h e r c r y ¼ c r y o f a n u n f a m i l i a r b a b y ; o w n c r y ¼ c r y o f t h e s u b j e c t ’ s o w n b a b y ; M P O A

¼ m e d i a l p r e o p t i c a r e a ; B N S T

¼ b e d n u c l e u s o f t h e s t r i a

t e r m i n a l i s .





T a b l e 4 H u m a n p a r e n t b r a i n r e s p o n s e s t o i n f a n t p i c t u r e s . A n a t o m i c a l b r a i n r e g i o n s w i t h i n c r e a s e d a c t i v i t y ( A C T ) d u r i n g i n f a n

t c r y a r e i n d i c a t e d i n g o l d , a n d a r e a s o f d e c r e a s e d a c t i v i t y

( D E A C T ) a r e i n d i c a t e d i n b l u e . E m p t y b o x e s i n d i c a t e n o s i g n i c a n t c h a n g e i n b r a i n a c t i v i t y w i t h e x p o s u r e t o b a b y p i c t u r e s

A u t h o r ( y e a r ) :

B a r t e l s &

Z e k i

( 2 0 0 4 )

N i t s c h k e e t a l .

( 2 0 0 4 )

R a n o t e e t a l .

( 2 0 0 4 )

S t r a t h e a r n &

M c C l u r e ( 2 0 0 2 )

S w a i n e t a l .

( 2 0 0 3 , 2 0 0 4 , 2 0 0 5 )

S w a i n e t a l .

( 2 0 0 3 , 2 0 0 4 , 2 0 0 5 )

N u m b e r o f

s u b j e c t s :

n ¼

1 9

n ¼

6

n ¼

1 0

n ¼

8

n ¼

9 – 1 4

n ¼

4 – 9

A g e o f i n f a n t s a t t i m e o f s c a n :

9 m o n t h s – 3 . 5

y e a r s

2 – 4 m o n t h s

4 – 8 m o n t h s

3 – 1 8 m o n t h s

t i m e 1 : 2 – 4 w e e k s

t i m e 2 : 3 – 4 m o n t h s

t i m e 1 : 2 – 4 w e e k s

t i m e 2 : 3 – 4 m o n t h s

P a r e n t a l g r o u p s :

m o t h e r s

o n l y





m o t h e r s


f a t h e r s

T y p e o f s t u d y :

2 T , 1 5 s b l o c k s


1 . 5 T , 3 0 s b l o c k s

x e d e f f e c t s

1 . 5 T , 2 0 – 4 0 s b l o c k s

r a n d o m e f f e c

3 T , 6 s e v e n t s

x e d e f f e c t s

3 T , 3 0 s b l o c k s x e d

e f f e c t s

3 T , 3 0 s b l o c k s

x e d e f f e c t s

B a b y p i c t u r e u s e d :

o w n > o t h e r

o w n > o t h e r

o w n > o t h e r v i d e o s

o w n > o t h e r

o w n

> o t h e r

b a b y

> h o u s e

o w n

> o t h e r

b a b y

> h o u s e

S e p t a l r e g i o n s ( M P O A / V B N S T /

c a u d a t e h e a d )

A C T

H y p o t h a l a m u s

A C T

T h a l a m u s

A C T

A C T

A C T

A C T

A C T

A C T

A C T

S t r i a t u m / p u t a m e n / n u c l e u s

a c c u m b e n s

A C T

A C T

A C T

A C T

A n t e r i o r c i n g u l a t e

A C T

A C T

A C T

A C T

A C T

M i d d l e c i n g u l a t e

A C T

A C T

A C T

A C T

P o s t e r i o r c i n g u l a t e

D E A C T

A m y g d a l a

D E A C T

A C T

L e n t i f o r m n u c l e u s G l o b u s

p a l l i d u s

A C T

A C T

A C T

H i p p o c a m p u s

A C T

A C T

M i d b r a i n

A C T

A C T

A C T

A C T

A C T

I n s u l a

A C T

O r b i t o f r o n t a l / i n f e r i o r f r o n t a l

A C T

A C T

A C T

A C T

A C T

A C T

M e d i a l f r o n t a l g y r u s

D E A C T

D E A C T

A C T

A C T

V e n t r a l p r e f r o n t a l

A C T

T e m p o r o p a r i e t a l

D E A C T

A C T

A C T

A C T

A C T

P a r a h i p p o c a m a l / L i m b i c l o b e

A C T

O c c i p i t a l c o r t e x

A C T

A C T

A C T

A C T

A C T

A C T

A C T

F u s i f o r m g y r u s

A C T

A C T

A C T

A C T

A C T

A C T

A C T

T e m p o r a l / A u d i t o r y c o r t e x

A C T

C e r e b e l l u m

A C T

A C T

A C T

A C T

A C T





even more active in parents during the early post-partum than at other times of life.

Parental brains and baby cry stimuli

The rst experiments using the pioneering approach

of studying brain activity in mothers while they listento infant cries was done by Lorberbaum and col-leagues. Building on the thalamocingulate theory of maternal behavior in animals developed by MacLean(1990), they initially predicted that baby cries wouldselectively activate cingulate and thalamus inmothers (ranging from 3 weeks to 3.5 years post-partum) exposed to an audio-taped 30-secondstandard baby cry, not from their own infant (Lor-berbaum et al., 1999), although they later expandedtheir hypotheses to include the MPOA/BNST and itsconnections including its indirect connections tomotivational circuitry (Lorberbaum et al., 2002). Intheir rst study (Lorberbaum et al., 1999), a group of 4 mothers were studied for their response to30 seconds of a standard cry compared with30 seconds of a control sound consisting of whitenoise that was shaped to the temporal pattern andamplitude of the cry. With cry versus control sound,the 4 mothers showed increased activity in the sub-genual anterior cingulate and right mesial prefron-tal/orbitofrontal using a xed effects data analysis.In a methodologically more stringent follow-upstudy, brain activity was measured in 10 healthy,breastfeeding, rst-time mothers with infants

1–2 months old. While they listened to standard in-fant cry recordings compared to similarly cry-shapedcontrol sounds, brain activity in many candidateparenting centers was revealed using a random ef-fects imaging analysis, in which posterior regionswere not imaged (Lorberbaum et al., 2002). Activatedregions included the anterior and posterior cingu-late, thalamus, midbrain, hypothalalamus, septalregions, dorsal and ventral striatum, medial pre-frontal cortex, right orbitofrontal/insula/temporalpolar cortex region, and right lateral temporal cortexand fusiform gyrus. Additionally, when cry responsewas compared with the inter-stimulus rest periods,instead of the control sound (which some mothers judged to be aversive), the amygdala was active. Thefusiform gyrus activity is interesting because thisstructure has been implicated in human face andvoice recognition along with related social cognitionsthat might be impaired in autism (Schultz, 2005).

These initial studies t with the regions thought tobe involved in animal parenting behavior. In thisstudy, brain activations occurred for these cries eventhough they did not originate from the parent’s owninfant and the control sounds were emotionallynegative (sounded like static on the television). Per-

haps then, this activity might partly represent in-creased attention to cries compared to controlsounds, rather than ‘parenting’ responses per se. This is suggested by related research on auditory

event-related brain potentials (ERPs). For example, Tzourio and colleagues showed that auditory atten-tion requires anterior cingulate and temporal corti-ces (Tzourio et al., 1997). In another study, womenresponded signicantly more to a baby cry than to anemotionally neutral vocalization in these regions

(Purhonen, Paakkonen, Ypparila, Lehtonen, & Kar-hu, 2001) and in a third study, mothers respondedmore than control women to infant cries (Purhonenet al., 2001). These results suggest a general in-crease in alertness and arousal for baby signals andfor mothers in particular, perhaps assisting them intheir ability to be continuously alert or be attuned tothe infant’s needs. It is not clear yet how much theN100 signal represents general arousal versusselective parenting attention per se. In the end, theargument here might be merely semantic as wewould expect attention and arousal to be importantelements of response to infant crying. Support forthis view might be found in studying parents whoabuse or neglect their children and might be havingdifculty sustaining or appropriately modulatingtheir attention and arousal in response to infantcries. In one such physiological study of parents whomaltreat their children (Frodi & Lamb, 1980),audiovisual infant stimuli elicited exaggeratedphysiological responses. Indeed, infant crying is aproximate risk factor for infanticide (Soltis, 2004),perhaps due to parents’ failure to regulate theirarousal. Future work may shed light on this ques-tion: What is unique about a healthy parent’s brain

compared to a parent at risk for neglect and abuse?One might think that healthy parents would attendto infant cues and respond appropriately, but not beso aroused as to make an impulsive, disinhibiteddecision. We hypothesize that this capacity to as-sume a caretaking role in the face of ostensiblyaversive stimuli may have measurable brain activitysignals.

Hypothesizing that gender and experience wouldaffect the neural responses to baby sounds includingbaby cry and laughter, Seifritz and colleagues (Seif-ritz et al., 2003) studied four groups: mothers andfathers of children under age 3, and non-parentmales and females, with 10 subjects in each group. They used an event-related fMRI design, whichmeasures brain response to brief 6-s events. Overthe entire sample, intensity-matched baby sounds of crying and laughing compared to ‘neutral’ sounds(white noise pulsed at 5-Hz with an averaged fre-quency spectrum similar to the infant vocalizations)produced more brain activity in bilateral temporalregions. These regions might be important for hear-ing processes (Heshyl’s gyrus and temporal poles),processing human vocalizations, and empathicemotion processing (see below). They also reported

that women, as a group including parents and non-parents (but not males), had a decrease in activity inresponse to both baby cry and laughter in the sub-genual anterior cingulate cortex. This nding is,





however, contrary to the other studies (Lorberbaumet al., 1999, 2002; Swain et al., 2003, 2004; Swain,Leckman, Mayes, Feldman, & Schultz, 2005), whichhighlights the importance of the choice of stimuli inthese experiments as well as not viewing the anteriorcingulate as one structure without subdivisons.

Perhaps also, 6-second vs. 30-second stimuli havevery different meanings to new parents and theremay be non-linear or biphasic anterior cingulate re-sponses. Finally, within-group analyses showed thatparents activated more to infant crying than laugh-ing in the right amygdala, while non-parent responsewas greater for infant laughing then crying (Seifritzet al., 2003). These within-group results suggest apotential change in amygdala function with being aparent, although there was no direct comparison of parents to non-parents. Inclusion of psychologicalmeasures of parenting parameters will make futurestudies more practically insightful. These data do,however, represent the rst attempts to extend theprevious work on parental brain circuits to includegender and experience-dependant aspects of humanparenting.

Relevant to parent responses to infant sounds,other fMRI research has been exploring brain re-sponses to emotionally laden human vocalizations,such as having non-parents listen to adult cries andlaughter. Some of the brain responses overlap withthose found in the parent–infant studies. To revealemotion circuits, subjects were asked to self-inducehappy or sad emotions to correspond with the

laughing or crying stimuli respectively. For pitchdetection, subjects were asked to detect pitch shifts.Both conditions led to bilateral activation of the a-mygdala, insula and auditory cortex with a right-hemisphere advantage in the amygdala, and largeractivation during laughing than crying in the audit-ory cortex with a slight right-hemisphere advantagefor laughing, both likely due to acoustic stimulusfeatures. These results suggest that certain brainregions, including the amygdala, activate to emo-tionally meaningful sounds like laughing and cryingindependent of the emotional involvement, suggest-ing the pattern recognition aspect of these sounds iscrucial for this activation and that emotional valencemight be represented elsewhere in the brain (Sander,Brechmann, & Scheich, 2003). Frontal areas may begood candidates as suggested by more recent workby Sander and colleagues, in which they found acorrelation between activity in the orbitofrontal cor-tex in response to angry utterances and an emotionalsensitivity scale across a group of young adults(Sander et al., 2005).

In an attempt to further this research on theneurocircuitry underlying emotionally laden par-enting behavior and parent–infant attachment, the

authors and their colleagues have been gatheringdatasets on groups of new parents across a range of experience, temperament and parent–infant inter-action styles using own baby cries. For example,

Swain and colleagues (Swain et al., 2003) reportedon a comprehensive interview and self-reportassessment and fMRI brain imaging (using own in-fant cry stimuli) of postpartum mothers and fathers,across experience from novice to multiple pregnancyfamilies. In this design, inspired by Lorberbaum and

colleagues (described above), parents underwentbrain fMRI during 30-second blocks of infant criesgenerated by their own infant as well as a ‘standard’ cry and control noises matched for pattern andintensity. In addition, they added a longitudinalcomponent with scans and interviews done at 2 timepoints: 2–4 weeks and 12–16 weeks postpartum. These times were chosen to coincide with the trans-forming experience of having a baby known to beassociated with increased tendency for parents to behighly preoccupied in the early postpartum (Leck-man et al., 1999). They hypothesized that parentalresponses to own baby cries would include specicactivations in thalamo–cortico–basal ganglia circuitsbelieved to be involved in human ritualistic andobsessive-compulsive thoughts and behaviors (Bax-ter, 2003; Leckman et al., 2004). Swain and col-leagues also reasoned that emotional alarm, arousaland salience detection centers including amygdala,hippocampus and insula (Britton et al., in press;LeDoux, 2003) would be activated by baby crystimuli. The experimental block design was used inorder to give parents a chance to reect on theirexperience of parenting and, according to our hypo-thesis, become more preoccupied with their infants’

well-being and safety. In a group of rst-time moth-ers ( n ¼ 9) at 2–4 weeks postpartum, own baby crystimuli compared with other baby cry regions of relative activation included midbrain, basal ganglia,cingulate, amygdala and insula (Swain et al., 2003).Preliminary analysis of the parenting interview datashows that mothers were signicantly more pre-occupied than fathers, which was reected in therelative lack of activation for fathers in the amygdalaand basal ganglia (Swain et al., 2004). In the groupof primiparous mothers, given the same stimuli at3–4 months postpartum, amygdala and insularactivations were not evident; and instead, medialprefrontal cortical and hypothalamic (hormonalcontrol) regions were active (Swain et al., 2004). Thismay reect a change in regional brain responses asthe parent–infant relationship develops, and themother learns to associate her infant cries more withsocial behaviors and habit systems, and less withalarm and anxiety. Manuscripts are in preparationto include data grouped across different variables,and include correlations between brain activity inregions of interest with measures of parental preoc-cupations and parent–infant behaviors.

Parental brains and baby visual stimuli

Several groups are using baby visual stimuli toactivate parental brain circuits (Bartels & Zeki,





2004b; Leibenluft, Gobbini, Harrison, & Haxby,2004; Nitschke et al., 2004; Ranote et al., 2004;Strathearn, 2002; Strathearn, Li, & Montague, 2005;Swain et al., 2003) with a variety of designs, parentpopulations and infant age.

Hypothesizing that reward and emotion circuits,

which are important for aspects of romantic love(Bartels & Zeki, 2000), might also be involved inmaternal love, Bartels and Zeki used photographs of own, familiar and unfamiliar infants (9 months to3.5 years of age) as stimuli for parental brain circuits(Bartels & Zeki, 2004b). They measured brain ac-tivity in 20 healthy mothers while viewing still-facephotographs of their own child compared to age-matched photographs of other children. There wasincreased activity in the midbrain (periaqueductalgray and substantia nigra regions), dorsal and ven-tral striatum, thalamus, left insula, orbitofrontalcortex, sub-, pre-, and supra-genual anterior cin-gulate, and superior medial prefrontal cortex. Therewere also increases in the cerebellum, left fusiform,and left occipital cortex, but decreases in the leftamygdala. Bartels and Zeki also compared motherbrain responses of own child vs. familiar child to thebest friend vs. familiar friend in order to control forfamiliarity and positive affect, and they argue thatresponses were unique to the own child stimuli. Theysuggested that parent–infant attachment may beregulated by a push–pull mechanism that selectivelyactivates motivation and reward systems, while atthe same time suppressing circuits responsible for

critical social assessment and negative emotions(Bartels & Zeki, 2004b).Using a similar approach, but focusing on early

stage romantic love, attachment and mate selection(Fisher et al., 2002; Fisher, Aron, Mashek, Li, &Brown, 2002), Aron, Fisher and colleagues con-ducted fMRI studies of brain response to photo-graphs of beloved and familiar individuals (Aronet al., 2005; Fisher, Aron, & Brown, 2005). Theyreplicated the ndings of Bartels and Zeki (Bartels &Zeki, 2000) and also reported activations specic tothe beloved in the midbrain (right ventral tegmentalarea) and the caudate nucleus (right postero-dorsalbody and medial parts). The activation in thesedopamine-rich areas associated with mammalianreward and motivation were correlated with facialattractiveness scores. Further, activation in the rightanteromedial caudate was correlated with question-naire scores that quantied intensity of romanticpassion for the individuals whose photographs wereused as stimuli. Also, activity in the left insula-putamen-globus pallidus correlated with trait affectintensity, wheras activity in limbic cortical regions,including insula, cingulate parietal, inferior tem-poral and middle temporal cortex was correlated

with the length of time in love. Taken together, thesestudies suggest that romantic love uses subcorticalreward and motivation systems to focus on a specicindividual, while limbic cortical regions process

individual emotion factors. The inverse approach toattachment circuits was taken by Najib, Lorber-baum, Kose, and colleagues (Najib, Lorberbaum,Kose, Bohning, & George, 2004). In this study of women whose romantic relationship had endedwithin the 4 months preceding the experiment, they

found that acute grief related to the loss of aromantic attachment gure modulated activity insome of the same areas implicated in social attach-ment and parenting. This included activations intemporal cortex, insula and prefrontal cortex. Incontrast to the romance-studies which found acti-vations in the anterior cingulate, they also foundthat romantic grief was consistently associated withdeactivations in this region. Finally, they found thatactivity in the anterior cingulate, insula, and amyg-dala was inversely related to the grief inventoryscore.

Returning to the focus of parent–infant relations,Swain and colleagues presented blocks of own andother baby photographs (aged 0–2 weeks) to groupsof mothers and fathers with similar block design forpictures as was used for cries (Swain et al., 2003).Photographs were chosen by the parents themselvesin order to provide the most potent and ethologicallyappropriate signals to evoke their own parentingemotions involving motivation and reward. In thesestudies, there were also activations in frontal andthalamo-cortical circuits to own vs. other baby pic-tures at 2–4 weeks postpartum. Specic characteri-zation of these regions according to differences by

gender, experience and postpartum time of assess-ment are under way.In a related study using photographs of much

older children (5–12 years), mothers viewed picturesof their own and other children’s faces during brainfMRI measurements, while being asked to press abutton to indicate identity (Leibenluft, Gobbini,Harrison, & Haxby, 2004). Some social cognitionregions that were not activated in the Bartels andZeki study (2004b) were signicantly activated inthis study, including the anterior paracingulate,posterior cingulate and the superior temporal sul-cus. This may be explained by the use of much olderchildren, which might involve a different set of cir-cuits relevant to those particular relationships. Itmay also be that the cognitive task interacts withaffective responses to face images in some way (Gray,2001). Differences in child photo affective facial ex-pressions (happy vs. neutral vs. sad) may also con-stitute a confounding factor. Another possiblereason for differences between studies is that samplepopulations and their relationships likely differ inimportant ways. Although all of the studies were of ‘normative’ parent populations, most studies onlyscreened for clinical psychiatric disease. It appears

that different populations may process infant cues indifferent ways. Perhaps studies involving more spe-cic tasks and correlations between brain activa-tions and relationship-specic variables will be able





to tease apart the particular roles of different brainregions in different aspects of those relationships.

Across auditory and visual sensory stimuli thusfar used in parent imaging studies, a convergence of brain responses is emerging to include many re-gions. Although baby cries may be aversive com-

pared with baby pictures, considerable overlap inactivation of motivation, arousal and reward circuitsmay not be too surprising since, for example, parentsare still generally compelled to approach a cryinginfant – perhaps in anticipation of reward. It alsomakes sense that common social cognition circuitswould be involved. In particular, it is interesting toconsider the common activation of the precuneuscortex in parents responding to own child stimuliacross visual and auditory stimuli (Leibenluft, Gob-bini, Harrison, & Haxby, 2004; Swain, Leckman,Mayes, Feldman, & Schultz, 2005). This ts with therapidly expanding literature on the importance of this region for episodic memory retrieval necessaryfor recognizing familiar auditory and visual socialstimuli, as well as self-referential mental imagery(Cavanna & Trimble, 2006; Gobbini & Haxby, inpress; Lundstrom, Ingvar, & Petersson, 2005;Lundstrom et al., 2003; Nakamura et al., 2001; Todorov, Gobbini, Evans, & Haxby, in press).

In another study focusing on parents’ brains usingvisual stimuli, Nitschke and colleagues studied sixhealthy, primiparous mothers’ brains at 2–4 monthspostpartum as they viewed smiling pictures of theirown and unfamiliar infants. They reported orbito-

frontal cortical activations that correlated positivelywith pleasant mood ratings. In contrast, areas of visual cortex that also discriminated between ownand unfamiliar infants were unrelated to mood rat-ings (Nitschke et al., 2004). Perhaps, as they sug-gest, activity in the orbitofrontal cortex – which mayvary across individuals – is involved with high orderdimensions of maternal attachment. Perhaps thecomplex aspects of parenting may be quantiedusing fMRI of frontal brain areas to help predict therisks of mood problems in parents.

With the innovative and perhaps more realisticand ethologically appropriate use of videotape infantstimuli, Ranote and colleagues conducted a similarexperiment (Ranote et al., 2004). In their study, 10healthy mothers viewed alternating 40-secondblocks of their own infant’s video, a neutral video,and an unknown infant. For these women, there wassignicant activation in the ‘own’ versus ‘unknown’ infant comparison in the left amygdala and temporalpole. They interpreted this circuit as regulatingemotion and theory-of-mind regions relating to theability to predict and explain other people’s behav-iors. Certainly, this ts with fMRI experiments onbiological motion, which activate similar regions

(Morris, Pelphrey, & McCarthy, 2005). It is importantto note that all of these visual paradigms used toexamine differences between one’s own infant andunfamiliar infants employ a complex set of brain

systems necessary for sensory perception, identi-cation, and emotional response. Yet, it now appearsfrom a number of studies that despite the multi-sensory complexities of audiovisual stimuli, mean-ingful analysis of fMRI data is possible. For example,there seems to be a striking inter-subject synchron-

ization among emotion regulating brain areasresponding to audiovisual cues during observationof the same scenes of an emotionally powerful movie(Hasson, Nir, Levy, Fuhrmann, & Malach, 2004).Also, the intensity with which subjects perceive dif-ferent features in a movie (color, faces, language, andhuman bodies) was correlated with activity in sepa-rate brain areas (Bartels & Zeki, 2004a). Finally,regional activity between brain areas that are knownto be anatomically connected has been shown to besimultaneously active during movie viewing (Bartels& Zeki, 2005). This work suggests the use of moviesas more naturalistic baby stimuli for parents mayalso be used to develop a functional architecture of brain parenting brain systems. Perhaps related de-cision-making can also be studied with interactivestimuli in future parent–infant brain imaging work.

Finally, Strathearn and colleagues have also beenstudying healthy mother–infant dyads using fMRI toexamine maternal brain regions activated in re-sponse to visual infant facial cues of varying affect(smiling, neutral and crying). They have completed apilot study of eight healthy right-handed mothers,without a history of psychiatric impairment or childmaltreatment along with their infants aged between

3 and 8 months. They assessed serum oxytocin lev-els sequentially from the mothers during a stan-dardized period of mother–infant interaction, duringwhich they acquired infants’ facial expressionvideotapes. Maternal brain activity was then assayedwith fMRI in response to 6-second exposures to thefacial images of their own infant compared withfamiliar and unknown infant facial images (Strath-earn, 2002). Areas of signicant activation (uncor-rected p < .005) unique to own infant viewingincluded brain reward areas with dopaminergicprojections (ventral striatum, thalamus and nucleusaccumbens), areas containing oxytocin projections(amygdala, bed nucleus of the stria terminalis andhippocampus), the fusiform gyrus (involved in faceprocessing), and bilateral hippocampi (involved inepisodic memory processing). Further, a positive,but non-signicant trend in this small sample wasseen in serum oxytocin concentration before andafter mother–infant interaction (prior to scanning),suggesting a possible correlation between brain ac-tivation and peripheral afliative hormone produc-tion. A further study, which was limited to thepresentation of crying infant faces, revealed activa-tion of the anterior cingulate and insula bilaterally

(Strathearn, Li, & Montague, 2005).Careful use of a variety of baby stimuli to activate

parent brains, along with correlations of parentalbrain activity with psychometric parameters, will





help in the understanding of these circuits. It mayalso be helpful to include comprehensive measure-ments of parent physiology during infant response.In addition to understanding normal parental be-havior, this eld promises to elucidate abnormalitiesof parental circuitry that may be manifest in post-

partum depression and anxiety. Such under-standing may suggest optimal detection andtreatment strategies for these conditions that haveprofound deleterious effects on the quality of parent– infant interactions, and the subsequent long-termhealth risks and resiliencies of infants. These studieswill also inform our understanding of social circuitsimportant for empathy across a range of relation-ships.

The neurobiology of empathy and parenting

Empathy, dened as appropriate perception, experi-ence and response to another’s emotion, is especiallyrelevant to parenting in which the infant’s needs aregreat, yet most communication is exclusively non-verbal. The growing eld of cognitive neuroscience,propelled by modern brain imaging techniques, isrevealing networks of brain activity relating toempathy and emotional mirroring (Gallese, Keysers,& Rizzolatti, 2004) that seem to overlap signicantlywith parenting brain responses reviewed in thispaper, and relevant to the brain basis of social cog-nition. Two of these overlapping regions are the cin-

gulate and insular cortices. Indeed, empathy hasbecome one of the central interests of psychodynamicclinicians, particularly since the writings of Kohut(Kohut, 1982), and we are now in a position to explorethe neuroanatomy.

In one fascinating study, focusing on the neuroa-natomy of empathy using fMRI techniques, Singerand colleagues measured brain activity while volun-teers experienced a painful stimulus or observed asignal indicating that their loved one (‘other’), presentin the same room, had received a similar pain sti-mulus (Singer et al., 2004). They found a separationof circuits responding to the sensory-discriminitativecomponents of pain from the autonomic-affectiveaspects. Specically, posterior insula, the sensori-motor cortex, and the caudal anterior cingulate,brainstem and cerebellum were active while receivingpain stimuli, yet for the emotional aspects of experi-encing the pain of a loved one, the rostral anteriorcingulate and anterior insula were specically active.Such decoupled representations, which may even beindependent of the sensory inputs of the outsideworld, have been postulated to be necessary for ourempathic abilities to mentalize, that is, to understandthe thoughts, beliefs, and intentions of others (Frith

& Frith, 2003). It may well be that humans useseparate circuits to decouple representations of theexternal world to understand physical properties andassess personal emotional values. This framework

may be of great importance to those studying thebrain substrates of relationships, as well as trau-matic stress disorder, dissociation, and our imagi-nation – which may occur without any real sensoryexperience.

In another relevant study of the cingulate in

mediating the brain basis of social behavior, Eisen-berger and colleagues utilized virtual reality tosimulate shunning. In this study (Eisenberger,Lieberman, & Williams, 2003), the subject is in-volved in a virtual game of Cyberball which includesthree players. Suddenly, the subject player is ex-cluded from the virtual game and there is a rapidchange in the anterior cingulate cortex. Perhaps thecingulate mediates the separation/attachment sys-tem, which may be so important to parenting, thedevelopment of the individual and in the work of thepsychoanalyst. Thus, in addition to registering pain,anterior cingulate may also be an important circuitin thinking about a range of emotional signals (painof oneself or social pain such as in witnessing thepain of a loved one, social rejection, or stimuli of one’s child or romantic love) in order to shift atten-tion, make decisions, recruit memory, regulatemood, or direct behavior.

The insula has also been raised as an importantcenter for integrating emotional information (Carr,Iacoboni, Dubeau, Mazziotta, & Lenzi, 2003) withconnections to mirror areas in the posterior parietal,inferior frontal, and superior temporal cortices alsoof interest. In one study subjects were shown pic-

tures of standard emotional faces (happy, sad, an-gry, surprised, disgusted, and afraid) and fMRI wasused to measure responses to two behavioral tasks:(i) mere observation and (ii) observation as well asinternal simulation of the emotion observed. As ex-pected, imitation produced greater activity in fron-totemporal areas in the mirror network, includingthe premotor face area, the dorsal pars opercularis of the inferior frontal cortex, and the superior temporalsulcus. Imitation also produced greater activity inthe right anterior insula and right amygdala. This isparticularly intriguing in light of evidence that theanterior insula responds to pleasant ‘caress-liketouch’ (Olausson et al., 2002) and that the insulaplays a crucial role in emotional and interpersonalinteraction in health and mental illness such asautism (Dapretto et al., 2006). A further conrma-tion of the insula’s role in emotion recognition comesfrom the study of patients with strokes. Stroke pa-tients with insular lesions showed a signicantlygreater decit in emotion recognition than otherstroke patients (Bodini, Iacoboni, & Lenzi, 2004). Wespeculate that cingulate and insula will continue toemerge as key areas of importance during thetransformations that are typical in the initial for-

mation of a new family. Perhaps studies of high-riskfamilies may fail to show this pattern of activation,while early intervention programs shown to havebenecial long-term effects on child development





(Olds et al., 2004) will be associated with changes inthe activation patterns seen in these limbic corticalregions.

Conclusions and critical summary

Forming strong interpersonal bonds involves under-standing the needs of the other, providing care andprotection, and a preoccupation with the interestsand wants of the other. The human transition toparenthood involves a set of highly conserved be-haviors and mental states, reecting both geneticendowment and early life experience – including theintrauterine environment not covered in this review.Indeed, while we have focused on parenting, there aremany other forms of interpersonal relationship – adoption, foster care, step-parenting, teaching,mentoring, grandparenting as well as friendship andromantic love – each involving similar genetic, neu-robiological and experiential systems that have thepotential to inform clinical practice, particularly earlyintervention programs for high-risk expectant par-ents. To paraphrase Winnicott (1960), ‘good enough’ genes combined with good enough parental careensure positive outcomes in childhood and beyond.

Unfortunately, ‘good enough’ circumstances areoften not available. Each year in the United States,over 900,000 children become victims of abuse orneglect, with the biological mother identied as aperpetrator in two-thirds of these cases (U.S. Dept. of

Health and Human Services, 2001, 2003). Abuseand neglect perpetrated by a child’s biological mo-ther represents a fundamental breakdown in thisimportant attachment relationship, resulting inserious long-term consequences for the offspring.Accumulating evidence from basic, clinical andepidemiological research indicates that the mother– infant relationship may be a critical target in opti-mizing developmental outcomes and preventingchild maltreatment (Olds et al., 1997; Sanchez,Ladd, & Plotsky, 2001). Measures of ‘primary par-ental preoccupations’ will be useful in future earlyintervention programs as an index of change within akey domain of functioning. Viewing parenting as aninteraction among genes, past parenting, currentexperience, psychological state, neurobiologicalsystems, and environmental constraints bringsmany disciplines to the study of parenting. Futuremultidisciplinary studies should permit the exam-ination of how successful early intervention pro-grams inuence brain development, problem-solvingabilities, stress response, as well as later parentingability and vulnerability to psychopathology. Thismay have far-reaching consequences for humanmental health. In fact, we expect that with a better

understanding of the neurobiological processesunderlying this reciprocal attachment relationship,we will be better able to understand – and ultimatelyhelp to prevent – child abuse and neglect.

Functional MRI experiments on parenting usingbaby stimuli are just beginning to make a meaning-ful contribution. This selective review of the physi-ology of parenting across species predicts manybrain areas that are likely important in regulatinghuman parenting. For this review, virtually all of the

studies involving infant stimuli to study parentbrains with fMRI are summarized and contrasted in Table 3 and 4 (baby cry stimuli), (baby picturestimuli). So far, it appears that a set of brain circuitsof parental response to baby stimuli, whether pictureor cry, is emerging. This appears to center on thecingulate with feedback loops involving midbrain,basal ganglia regions and thalamus for motivationand reward. More complex planning and socialemotional/empathy responses may involve frontal,insular, fusiform and occipital areas. Other import-ant aspects of parenting may be contributed bycontext and memory processing regions includingthe hippocampus, parahippocampus and amygdala.Clearly, baby pictures and cries can be used toselectively activate brain circuits related to arousal,mood, and social and habitual behaviors. However,different groups have used a mixture of stimuliincluding baby cries, laughter and child pictures of very different ages and different facial affect andexperience. A clearer picture of the specicity of different brain areas may emerge as brain responsesin these areas are linked to specic aspects of parenting, by adding sophisticated interviews, nat-uralistic assessments of parent–infant interaction

and bonding. This review is an attempt to synthesize our currentunderstanding of parent–infant bonding, largelyfrom the perspective of the parent’s brain physiology. The parent–infant bond, so central to the humancondition, may also determine risks for mood andanxiety disorders, and potential for resiliency andprotection against the development of psychopa-thology later in life, not to mention the far-reachingaspects of human attachment across individual be-haviors and between cultures. Efforts to characterizethis reciprocal interaction between caregiver andinfant and to assess its impact have provided apowerful theoretical and empirical framework in theelds of social and emotional development.

Future directions

Likely, the stimuli and populations will be expandedand rened in parental brain research to include theuse of more movie stimuli and the different sensorysystems such as the olfactory system. This will re-quire careful consideration and study of how thesepatterns of brain activation may differ between

attachment groups. Do mothers with insecure pat-terns of attachment respond differently to their in-fant cues? Are neglecting mothers unresponsive tothese cues or do they fail to receive reward signals in





the brain? Longitudinal research designs may helpin this regard. In addition, it will be important toclarify the role of different neuroendocrine pathwaysand different genetic variations in mediating par-enting brain activations.

A helpful approach to these questions will in-

clude systematic studies of well-characterized butdifferent populations of parents using a variety of infant stimuli paradigms and psychometric tools.As in other areas of cognitive neuroscience, therewill be debates about whether to use more etho-logically sound but poorly controlled versus moretightly controlled, but less generalizable stimuli.Both types of experiment will be needed to teaseapart the basic apparatus of baby responsivenessand bond formations as well as the parts of thecircuit that are actually at work in normal day-to-day-parenting. This work will also require jointstudy of parents and infants to understand howtheir interactions contribute to their bond andinfant outcomes.

In the near future, we expect that differences inparental response patterns will be reported in spe-cic clinical populations, such as those with post-partum depression and substance abuse. This maylead to future assessments of parent mental healthrisk and resilience proles using standardized ima-ging techniques and to improvements in the detec-tion, treatment and prevention of mental illness thatinterferes with parenting.

Acknowledgements

The authors would like to acknowledge the generoussupport of colleagues, research assistants and re-search participants at our respective institutions:

JES was supported by grants from the Institute forResearch on Unlimited Love (unlimitedloveinsti-tute.org), the National Alliance for Research onSchizophrenia and Depression (narsad.org), the YaleCenter for Risk, Resilience and Recovery, and Asso-ciates of the Yale Child Study Center. Dr. Swainwould especially like to acknowledge the mentorshipof Drs. James F. Leckman, Linda C. Mayes, andRobert T. Schultz.

JPL was supported by the child neglect consor-tium RFA grant, NINDS R01 NS40259–01, NICHD R-03 HD49422–01, the Center for Advanced ImagingResearch (CAIR) at the Medical University of SouthCarolina, the National Alliance for Research onSchizophrenia and Depression (narsad.org), andPenn State’s Child Youth and Family Consortium.Dr. Lorberbaum would especially like to acknow-ledge the ideas of Drs. Paul Maclean and MarkS. George in getting started in this line of research.

SK was supported by the child neglect consortiumRFA grant R-01 NINDS R01 NS40259–01, and theNational Alliance for Research on Schizophrenia andDepression (narsad.org)

LS was supported by grants from the NationalInstitute of Child Health and Human Development(K23 HD043097) and the Baylor CHRC: PediatricsMentored Research Program (K12 HD41648), andthe South Central MIRECC.

We gratefully acknowledge that Figure 1 and por-

tions of the text were reproduced with permissionfrom the book, Developmental Science and Psycho-analysis: Integration and Innovation, Ó 2007 LindaMayes, Peter Fonagy, Mary Target, London, UK.Published by Karnac, London, UK.

Correspondence to

James E. Swain, Child Study Center, Yale University,230 S. Frontage Road, New Haven, CT 06520-7900,USA; Tel: (203) 785-6973; Fax: (203) 785-7611;Email: [email protected]

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Brain Basis in Interaction With Children