Results of this study are the first, to our knowledge, to chart the coordinated functioning of neural networks, affiliation hormones, and micro-level maternal behavior in an attempt to further specify the neurobiological basis of mothering. Consistent with methodology developed in animal research and research showing that patterns of maternal care in mammals chart distinct bio-behavioral profiles in mothers, we examined two naturally occurring patterns of human maternal care—synchronous and intrusive mothering—and assessed their brain and neurohormonal correlates. The study is also among the first to assess maternal brain response to ongoing, dynamic, and ecologically valid infant stimuli and describe the neural networks associated with the synchronous and intrusive maternal styles on the basis of functional connectivity analysis. Similar to the analysis of the mother's brain response to an ongoing infant stimulus, our behavioral measures were defined on a temporal continuum and addressed the ongoing coordination between maternal behavior and infant social signals. The findings, therefore, may provide new insights into the interface between the maternal brain response and the moment-by-moment expression of maternal behavior in the formation of maternal–infant bonding in humans.
Overall, the results chart three functional neural networks that are activated in response to infant stimuli and may, in combination, describe the brain basis of human mothering. The first refers to a limbic motivational network that includes the NAcc and amygdala (Assaf et al, 2009
). The second is an attention network (Pessoa et al, 2002
) oriented at perception–action integration (Dayan et al, 2007
), which includes the IFG, medial frontal gyrus, associative visual areas, insula, pre-supplementary motor area and parietal cortices that are thought to compose the mirror–neuron network (Iacoboni and Dapretto, 2006
; Keysers and Fadiga, 2008
). The third network includes the mPFC emotional modulation areas (Bryant et al, 2008
; Gilboa et al, 2004
; Liddell et al, 2005
; Zaretsky et al, 2010
), which we found to be functionally correlated with the limbic activation of the left NAcc in the synchronous mothers and the right amygdala in the intrusive group. The discrete activations of these structures have been previously associated with maternal response to own infant stimuli (Bartels and Zeki, 2004
; Leckman et al, 2004
; Lorberbaum et al, 2002
; Swain et al, 2007
). Here, we describe the coordinated functioning of these three neural networks into a unified time-locked brain activity and suggest that this integration is related to the mother's social behavior. The finding that a unique integrative profile of the three neural systems emerged for mothers showing synchronous vs
intrusive styles of maternal care may suggest that addressing the coordination between various emotional and social brain systems can prove useful in the study of normative vs
The synchronous maternal style was characterized by four features. At the motivational level, the left NAcc in this group showed greater activations as compared to the right amygdala during the observation of own infant cues. This may suggest that the motivational mechanisms underlying synchronous maternal care are based on the reward components of parenting to a greater extent than on the stress elements. Second, at the connectivity level, the left NAcc in the synchronous group was functionally correlated with the left dmPFC and the right subcallosal ACC. In the context of rodent maternal behavior, these structures were found to control the motivational element of maternal behavior rather than the behavior per se
(Lorberbaum et al, 2002
; Slotnick, 1967
; Stamm, 1955
), whereas human research has implicated these structures in cognitive empathy and ‘Theory of Mind' skills (Assaf et al, 2009
; Gallagher and Frith, 2003
; Vollm et al, 2006
). In addition, in the synchronous maternal care group, functional connectivity was found between the right amygdala and regions included in the so-called MNS, including the STG, insula, and IFG. Such mirror system activations may reflect the mother's ability to better understand the intentions and desires of her infant and to respond with a synchronized conduct. Thirdly, the hormonal analysis revealed that among the synchronous group, plasma Oxytocin levels were correlated with the activation of the left NAcc and the right amygdala. Oxytocin is known to mediate social affiliation in mammals (Insel et al, 1997
), and thus the connection between Oxytocin and activations of these parenting-related motivational limbic areas may suggest that parenting for these mothers is more closely linked with subcortical motivational mechanisms. Finally, the SPIN analysis indicated that among the synchronous group, the time course of the left NAcc and right amygdala activations showed a relatively organized pattern across the paradigm, whereas the intrusive group displayed less organized activity of these nuclei. This study is the first to apply SPIN analysis in fMRI research of human attachment, and may thus open new directions for future research. Such analysis focuses on the organization of ROI activity across time, rather than on the direction of effects and underscores the importance of signal organization in the description of maternal care profiles.
In contrast to the synchronous group, the intrusive group was characterized by a different set of features. Among these mothers, right amygdala activations were significantly greater than left NAcc activations, suggesting that the motivational components of fear and anxiety may be more pronounced than those associated with reward and affiliation. In addition, the organizing activity of the dmPFC was missing in this group and wide activations of pro-action areas were observed, including the right premotor cortex and the left OFC. This pattern may point to insufficient behavioral inhibition, which may lead to the excessive, non-modulated maternal behavior typical of the intrusive style. Another feature that reflected intrusive mothering was the lower organization of the left NAcc and right amygdala across time. SPIN analysis revealed that the activity of these motivational nuclei showed lower levels of intrinsic organization in this group and this corresponded with their lower behavioral synchronization. Taken together, the findings chart distinct profiles of limbic and cortical activity and their time-locked integration that differentiated mothers whose caregiving style was characterized by affect synchrony from those whose behaviors were marked by overstimulation, excessive parenting, and miscoordination.
The correlations between the left NAcc and right amygdala activity with plasma Oxytocin in the synchronous group are interesting in light of recent findings on the role of Oxytocin in social affiliation. Oxytocin has been consistently implicated in the onset of maternal behavior in mammals and with more adaptive maternal care in humans (Feldman et al, 2010a
; Gordon et al, 2010a
; Levine et al, 2007
; Pedersen et al, 1994
). Oxytocin has also been linked with social approach behavior (Kosfeld et al, 2005
) and empathy (Domes et al, 2007
; Hurlemann et al, 2010
). Recently, the infusion of Oxytocin directly into rat mothers' ventral tegmental area was found to enhance dopamine signals in the NAcc shell and to increase maternal behavior (Shahrokh et al, 2010
). The involvement of NAcc dopamine in social reward, including maternal attachment, may be linked with Oxytocin projections. It is possible that social reward relies on different mechanisms than those implicated in other types of reward (eg, food) and that social reward depends to a greater extent on the functioning of the Oxytocinergic system (Strathearn et al, 2009
). Although the precise nature of such Oxytocin–dopamine interactions in the support of maternal behavior is not fully understood, their combined activity may be central to the formation of affiliative bonds (Douglas, 2010
; Strathearn et al, 2009
). Future endocrine, imaging, and animal studies are required to explore the relations between the Oxytocin and NAcc dopaminergic systems within a model that addresses their combined contribution to human attachment.
Results of this study may provide further insights on the adaptive roles of both the reward and stress components of parenting. The fact that the infant is a powerful reinforcement to its mother (Barrett and Fleming, 2011
) serves an important evolutionary role and may be mediated by the NAcc (Champagne et al, 2004
; Hansen, 1994
; Hansen et al, 1991
; Keer and Stern, 1999
; Li and Fleming, 2003
; Vernotica et al, 1999
). However, a certain amount of heightened arousal and vigilance is also required for infant care, which involves some anxious conduct (Barrett and Fleming, 2011
; Leckman and Herman, 2002
; Leckman and Mayes, 1999
; Leckman et al, 1999
). The amygdala, which processes negative emotions, may participate in directing attention toward the infant and charging the incentive value placed on the infant with acuteness and highly aroused energy. Such finely tuned co-activations of structures within the limbic system are central for the formation of the maternal–infant bond. However, this delicate balance is also highly sensitive to early disruptions and slight deviations from normative functioning may result in non-optimal patterns of maternal care that may bear negative consequences for the infant's future mental health. Indeed, recent studies have shown that up to 29% of mothers and infants suffer from some sort of disruptions to early bonding, due to marked increases in cases of maternal post-partum depression and anxiety, as well as in premature birth (ACOG, 2006
; Andersson et al, 2006
; Silverman et al, 2007
; Vesga-Lopez et al, 2008
). Such conditions pose a risk for the infant's adaptation and well-being and may lead to a variety of epigenetic, behavioral, and mental processes that would compromise the infant's future well-being, health, and adaptation.
The findings demonstrate that the motivational components of stress and affiliation are evident not only at the limbic level, but also at the cortical and mental levels. Synchronous mothers showed higher activations of mirror-neuron and empathy-related cortical systems, which may point to more adaptive theory-of-mind skills and more adequate representations of the infant's needs. Conversely, intrusive mothers consistently activated pro-action areas, which may explain the non-matched excessive maternal behavior and the lack of sufficient mentalizing of the infant's state. These results support the notion that in addition to conserved biological and behavioral aspects, human parenting includes higher-order mental components that involve the capacity to reflect on infant state, differentiate infant signals on the basis of past experience, and plan a course of caregiving actions. Such perception–action systems include primary and associative cortices of different modalities, premotor areas, and mirror neuron areas such as insula, STG, IFG, and parietal cortex that have been associated with empathy (Adolphs et al, 2000
; Rizzolatti, 2005
), theory-of-mind abilities (Gallagher and Frith, 2003
), and maternal response to infant cries (Swain et al, 2007
The findings that maternal synchrony and intrusiveness chart two unique profiles of brain–behavior correlations and that these associations did not emerge for the entire group is consistent with the findings for other mammals showing that distinct patterns of maternal care are underpinned by specific biological processes (Meaney, 2001
). Future research may extend research from patterns of maternal care observed in the normative population to profiles of brain–behavior correlations in clinical populations. Similarly, future research may integrate other physiological systems with constellations of observed parenting, including the immune system and epigenetic processes.
Two reasons guided our choice to sample plasma Oxytocin at the home and not in the hospital context, where the fMRI data was collected. First, most current knowledge on maternal plasma Oxytocin is based on samples collected in the home and it was important to compare our Oxytocin levels with previously published data. Second, we wished to avoid the potential anxiety-provoking effects of a blood draw on the mother's brain response (if sampled before imaging) or the effects of exposure to infant cues on Oxytocin levels (if sampled after imaging). Plasma Oxytocin levels were found to be highly stable within individuals in several independent samples (Gordon et al, 2010a
; Levine et al, 2007
) and to be unrelated to demographic conditions, such as parent gender, age, height, weight, body mass index, smoking, use of medications, and time since last meal. Similarly, when not sampled immediately before or after breastfeeding, maternal OT levels are unrelated to menstrual cycle phase, contraceptive intake, mode of delivery (vaginal vs
c-section), feeding style (breastfeeding vs
bottle-feeding), post-partum interval (weeks from birth to date of assessment), or the interval from prior breastfeeding (Feldman et al, 2010b
). Thus, our plasma Oxytocin levels likely reflect baseline levels that are not affected by the situational distress of the fMRI procedure.
Limitations of the study include the small number of intrusive mothers with Oxytocin data and future research with larger samples are required to better describe the hormonal profile of this group and its brain correlates. The father's data would have been important to shed light on the paternal brain and its relation to patterns of paternal care. Attachment patterns in infants were also not tested and this is clearly a study limitation. Assessing infant attachment would have pointed to the relations between bio-behavioral profiles of maternal care and infant attachment security vs
insecurity. In general, it is important to emphasize that our use of the term ‘attachment' was general and does not imply that infant attachment was studied. Such use is consistent with Bowlby's (1958
) description of the mother's attachment to her infant and its biological and behavioral concomitants. Furthermore, as brain, hormonal, and behavioral data were collected concurrently, it is not possible to infer causality, only relationships between variables. Follow-up data would have been important to examine whether maternal brain activations in the post-partum can predict infants' later social–emotional development and assessment of maternal Oxytocin during pregnancy could have shown predictions from hormonal levels to brain activations. Much further research is required to integrate imaging, hormonal analysis, and careful assessments of social behavior with genetic and epigenetic markers to help describe integrative profiles that may later assist in the diagnosis of specific high-risk conditions.
The use of functional magnetic resonance imaging combined with micro-level behavioral analysis and bonding-related hormones may enhance our understanding of typical and high-risk parenting. Our results show that a priori categorization of patterns of maternal care that are expressed in the general population can reliably chart different neural networks. Future research is required to apply integrative assessments to various clinical populations that involve risk to the mother–infant bond due to post-partum depression, premature birth, or social adversity. Understanding the motivational basis of healthy and at-risk parenting may open new theoretical vistas and clinical opportunities and may lead to the construction of more specific interventions that can target disruptions to maternal–infant bonding at an earlier stage and in a more accurate manner.