Skip to main content
    • Aa
    • Aa

Insensitive parenting may accelerate the development of the amygdala–medial prefrontal cortex circuit

  • Sandra Thijssen (a1) (a2), Ryan L. Muetzel (a2) (a3), Marian J. Bakermans-Kranenburg (a1), Vincent W. V. Jaddoe (a2), Henning Tiemeier (a2) (a3), Frank C. Verhulst (a2) (a3), Tonya White (a2) (a3) and Marinus H. Van Ijzendoorn (a1) (a4)...

This study examined whether the association between age and amygdala–medial prefrontal cortex (mPFC) connectivity in typically developing 6- to 10-year-old children is correlated with parental care. Resting-state functional magnetic resonance imaging scans were acquired from 124 children of the Generation R Study who at 4 years old had been observed interacting with their parents to assess maternal and paternal sensitivity. Amygdala functional connectivity was assessed using a general linear model with the amygdalae time series as explanatory variables. Higher level analyses assessing Sensitivity × Age as well as exploratory Sensitivity × Age × Gender interaction effects were performed restricted to voxels in the mPFC. We found significant Sensitivity × Age interaction effects on amygdala–mPFC connectivity. Age was related to stronger amygdala–mPFC connectivity in children with a lower combined parental sensitivity score (b = 0.11, p = .004, b = 0.06, p = .06, right and left amygdala, respectively), but not in children with a higher parental sensitivity score, (b = –0.07, p = .12, b = –0.06, p = .12, right and left amygdala, respectively). A similar effect was found for maternal sensitivity, with stronger amygdala–mPFC connectivity in children with less sensitive mothers. Exploratory (parental, maternal, paternal) Sensitivity × Age × Gender interaction analyses suggested that this effect was especially pronounced in girls. Amygdala-mPFC resting-state functional connectivity has been shown to increase from age 10.5 years onward, implying that the positive association between age and amygdala–mPFC connectivity in 6- to 10-year-old children of less sensitive parents represents accelerated development of the amygdala–mPFC circuit.

Corresponding author
Address correspondence and reprint requests to: Henning Tiemeier, Generation R Study Group, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands; E-mail:
Hide All

The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the Erasmus University Rotterdam, School of Law and Faculty of Social Sciences; the Municipal Health Service Rotterdam area, Rotterdam; the Rotterdam Homecare Foundation, Rotterdam; and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR), Rotterdam. The first phase of the Generation R Study is made possible by financial support from Erasmus Medical Centre, Rotterdam; Erasmus University, Rotterdam; the Netherlands Organization for Health Research and Development (ZonMw); the Netherlands Organisation for Scientific Research; the Ministry of Health, Welfare and Sport; and the Ministry of Youth and Families. In addition, this study is financially supported through ZonMw TOP project number 91211021 (to T.W.). Henning Tiemer, Marian J. Bakermans-Kranenburg, and Marinus H. van IJzendoorn were supported by research awards from the Netherlands Organization for Scientific Research (H.T., VIDI grant; M.H.v.I., SPINOZA prize; M.J.B.K., VICI grant), and by the Gravitation program of the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (Grant 024.001.003). Bakermans-Kranenburg was also supported by the European Research Council (ERC AdG).

Hide All
AinsworthM. D., & BellS. M. (1970). Attachment, exploration, and separation: Illustrated by the behavior of one-year-olds in a strange situation. Child Development, 41, 4967.
AinsworthM. S., BellS. M., & StaytonD. J. (1974). Infant-mother attachment and social development: “Socialization” as a product of reciprocal responsiveness to signals. In Richards M. P. M. (Ed.), The integration of a child into a social world (pp. 99135). Cambridge: Cambridge University Press.
AkiravI., & MarounM. (2007). The role of the medial prefrontal cortex-amygdala circuit in stress effects on the extinction of fear. Neural Plasticity, 2007, 30873.
AlarconG., CservenkaA., RudolphM. D., FairD. A., & NagelB. J. (2015). Developmental sex differences in resting state functional connectivity of amygdala sub-regions. NeuroImage, 115, 235244.
Bakermans-KranenburgM. J., van IJzendoornM. H., PijlmanF. T., MesmanJ., & JufferF. (2008). Experimental evidence for differential susceptibility: Dopamine D4 receptor polymorphism (DRD4 VNTR) moderates intervention effects on toddlers’ externalizing behavior in a randomized controlled trial. Developmental Psychology, 44, 293300.
BanihashemiL., SheuL. K., MideiA. J., & GianarosP. J. (2015). Childhood physical abuse predicts stressor-evoked activity within central visceral control regions. Social Cognitive and Affective Neuroscience, 10, 474485.
BelskyJ., RuttleP. L., BoyceW. T., ArmstrongJ. M., & EssexM. J. (2015). Early adversity, elevated stress physiology, accelerated sexual maturation, and poor health in females. Developmental Psychology, 51, 816822.
BelskyJ., SteinbergL., & DraperP. (1991). Childhood experience, interpersonal development, and reproductive strategy—An evolutionary-theory of socialization. Child Development, 62, 647670.
BernierA., CarlsonS. M., DeschenesM., & Matte-GagneC. (2012). Social factors in the development of early executive functioning: A closer look at the caregiving environment. Developmental Science, 15, 1224.
BirnR. M., MolloyE. K., PatriatR., ParkerT., MeierT. B., KirkG. R., … PrabhakaranV. (2013). The effect of scan length on the reliability of resting-state fMRI connectivity estimates. NeuroImage, 83, 550558.
BussK. A., BrookerR. J., & LeutyM. (2008). Girls most of the time, boys some of the time: Gender differences in toddlers’ use of maternal proximity and comfort seeking. Infancy, 13, 129.
CallaghanB. L., & RichardsonR. (2011). Maternal separation results in early emergence of adult-like fear and extinction learning in infant rats. Behavioral Neuroscience, 125, 2028.
CallaghanB. L., & TottenhamN. (2016a). The neuro-environmental loop of plasticity: A cross-species analysis of parental effects on emotion circuitry development following typical and adverse caregiving. Neuropsychopharmacology, 41, 163176.
CallaghanB. L., & TottenhamN. (2016b). The stress acceleration hypothesis: Eeffects of early-life adversity on emotion circuits and behavior. Current Opinion in Behavioral Sciences, 7, 7681.
CicchettiD. (2016). Developmental psychopathology. Hoboken, NJ: Wiley.
ConnerO. L., SiegleG. J., McFarlandA. M., SilkJ. S., LadouceurC. D., DahlR. E., CoanJ. A., & RyanN. D. (2012). Mom—It helps when you're right here! Attenuation of neural stress markers in anxious youths whose caregivers are present during fMRI. PLOS ONE, 7, e50680.
DannlowskiU., KugelH., HuberF., StuhrmannA., RedlichR., GrotegerdD., … SuslowT. (2013). Childhood maltreatment is associated with an automatic negative emotion processing bias in the amygdala. Human Brain Mapping, 34, 28992909.
DecetyJ., MichalskaK. J., & KinzlerK. D. (2012). The contribution of emotion and cognition to moral sensitivity: A neurodevelopmental study. Cerebral Cortex, 22, 209220.
DozierM., PelosoE., LewisE., LaurenceauJ. P., & LevineS. (2008). Effects of an attachment-based intervention on the cortisol production of infants and toddlers in foster care. Development and Psychopathology, 20, 845859.
EgelandB., EricksonM. F., Clemenhagen-MoonJ., HiesterM. K., & KorfmacherJ. (1990). 24 Months tool coding manual. Project STEEP—Revised 1990 from mother-child project scales. Unpublished manuscript, University of Minnesota, Minneapolis.
EllisB. J., SchlomerG. L., TilleyE. H., & ButlerE. A. (2012). Impact of fathers on risky sexual behavior in daughters: A genetically and environmentally controlled sibling study. Development and Psychopathology, 24, 317332.
FearonR. M. P., GrohA. M., van IJzendoornM. H., Bakermans-KranenburgM. J., & RoismanG. I. (2016). Attachment and developmental psychopathology. In Cicchetti D. (Ed.), Developmental psychopathology (pp. 325384). Hoboken, NJ: Wiley.
ForbesC. E., & GrafmanJ. (2010). The role of the human pefrontal cortex in social cognition and moral judgment. Annual Review of Neuroscience, 33, 299324.
FrazierJ. A., ChiuS. F., BreezeJ. L., MakrisN., LangeN., KennedyD. N., … BiedermanJ. (2005). Structural brain magnetic resonance imaging of limbic and thalamic volumes in pediatric bipolar disorder. American Journal of Psychiatry, 162, 12561265.
Gabard-DurnamL. J., FlanneryJ., GoffB., GeeD. G., HumphreysK. L., TelzerE., … TottenhamN. (2014). The development of human amygdala functional connectivity at rest from 4 to 23 years: A cross-sectional study. NeuroImage, 95, 193207.
GeeD. G., Gabard-DurnamL. J., FlanneryJ., GoffB., HumphreysK. L., TelzerE. H., … TottenhamN. (2013). Early developmental emergence of human amygdala-prefrontal connectivity after maternal deprivation. Proceedings of the National Academy of Sciences, 110, 1563815643.
GeeD. G., HumphreysK. L., FlanneryJ., GoffB., TelzerE. H., ShapiroM., … TottenhamN. (2013). A developmental shift from positive to negative connectivity in human amygdala-prefrontal circuitry. Journal of Neuroscience, 33, 45844593.
GieddJ. N., VaituzisA. C., HamburgerS. D., LangeN., RajapakseJ. C., KaysenD., … RapoportJ. L. (1996). Quantitative MRI of the temporal lobe, amygdala, and hippocampus in normal human development: Ages 4–18 years. Journal of Comparative Neurology, 366, 223230.
GriffantiL., Salimi-KhorshidiG., BeckmannC. F., AuerbachE. J., DouaudG., SextonC. E., … SmithS. M. (2014). ICA-based artefact removal and accelerated fMRI acquisition for improved resting state network imaging. NeuroImage, 95, 232247.
GuyerA. E., MonkC. S., McClure-ToneE. B., NelsonE. E., Roberson-NayR., AdlerA. D., … ErnstM. (2008). A developmental examination of amygdala response to facial expressions. Journal of Cognitive Neuroscience, 20, 15651582.
HahnA., SteinP., WindischbergerC., WeissenbacherA., SpindeleggerC., MoserE., … LanzenbergerR. (2011). Reduced resting-state functional connectivity between amygdala and orbitofrontal cortex in social anxiety disorder. NeuroImage, 56, 881889.
HaririA. R., MattayV. S., TessitoreA., FeraF., & WeinbergerD. R. (2003). Neocortical modulation of the amygdala response to fearful stimuli. Biological Psychiatry, 53, 494501.
HenschT. K. (2004). Critical period regulation. Annual Review of Neuroscience, 27, 549579.
HochbergZ., & BelskyJ. (2013). Evo-devo of human adolescence: Beyond disease models of early puberty. BMC Medicine, 11, 113.
HostinarC. E., JohnsonA. E., & GunnarM. R. (2015). Early social deprivation and the social buffering of cortisol stress responses in late childhood: An experimental study. Developmental Psychology, 51, 1597–608.
JaddoeV. W., van DuijnC. M., FrancoO. H., van der HeijdenA. J., van IJzendoornM. H., de JongsteJ. C., … HofmanA. (2012). The Generation R Study: Design and cohort update 2012. European Journal of Epidemiology, 27, 739756.
JenkinsonM., BeckmannC. F., BehrensT. E., WoolrichM. W., & SmithS. M. (2012). FSL. NeuroImage, 62, 782790.
KokR., LintingM., Bakermans-KranenburgM. J., van IJzendoornM. H., JaddoeV. W. V., HofmanA., VerhulstF. C., & TiemeierH. (2013). Maternal sensitivity and internalizing problems: Evidence from two longitudinal studies in early childhood. Child Psychiatry & Human Development, 44, 751765.
KokR., ThijssenS., Bakermans-KranenburgM. J., JaddoeV. W. V., VerhulstF. C., WhiteT., … TiemeierH. (2015). Normal variation in early parental sensitivity predicts child structural brain development. Journal of the American Academy of Child & Adolescent Psychiatry, 54, 824831.
KokR., van IJzendoornM. H., LintingM., Bakermans-KranenburgM. J., TharnerA., LuijkM. P. C. M., … TiemeierH. (2013). Attachment insecurity predicts child active resistance to parental requests in a compliance task. Child Care Health and Development, 39, 277287.
LucassenN., KokR., Bakermans-KranenburgM. J., van IJzendoornM. H., JaddoeV. W. V., HofmanA., … TiemeierH. (2015). Executive functions in early childhood: The role of maternal and paternal parenting practices. British Journal of Developmental Psychology, 33, 489505.
MaldjianJ. A., LaurientiP. J., KraftR. A., & BurdetteJ. H. (2003). An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. NeuroImage, 19, 12331239.
ManningL. G., DaviesP. T., & CicchettiD. (2014). Interparental violence and childhood adjustment: How and why maternal sensitivity is a protective factor. Child Development, 85, 22632278.
MehtaM. A., GolemboN. I., NosartiC., ColvertE., MotaA., WilliamsS. C. R., … Sonuga-BarkeE. J. S. (2009). Amygdala, hippocampal and corpus callosum size following severe early institutional deprivation: The English and Romanian Adoptees Study Pilot. Journal of Child Psychology and Psychiatry, 50, 943951.
MillerE. K. (2002). The prefrontal cortex and cognitive control. Perception, 31, 104.
MoriceauS., & SullivanR. M. (2006). Maternal presence serves as a switch between learning fear and attraction in infancy. Nature Neuroscience, 9, 10041006.
MoutsianaC., JohnstoneT., MurrayL., FearonP., CooperP. J., PliatsikasC., … HalliganS. L. (2015). Insecure attachment during infancy predicts greater amygdala volumes in early adulthood. Journal of Child Psychology and Psychiatry, 56, 540548.
MuetzelR. L., BlankenL. M. E., ThijssenS., van der LugtA., JaddoeV. W. V., VerhulstF. C., … WhiteT. (2016). Resting-state networks in 6-to-10 year old children. Human Brain Mapping, 37, 42864300. doi:10.1002/hbm.23309
MutluA. K., SchneiderM., DebbaneM., BadoudD., EliezS., & SchaerM. (2013). Sex differences in thickness, and folding developments throughout the cortex. NeuroImage, 82, 200207.
NelsonC. A., FoxN. A., & ZeanahC. H. (2014). Romania's abandoned children: Deprivation, brain development, and the struggle for recovery. Cambridge, MA: Harvard University Press.
NewtonE. K., LaibleD., CarloG., SteeleJ. S., & McGinleyM. (2014). Do sensitive parents foster kind children, or vice versa? Bidirectional influences between children's prosocial behavior and parental sensitivity. Developmental Psychology, 50, 18081816.
NormanR. E., ByambaaM., DeR., ButchartA., ScottJ., & VosT. (2012). The long-term health consequences of child physical abuse, emotional abuse, and neglect: A systematic review and meta-analysis. PLOS Medicine, 9, e1001349.
OchsnerK. N., BungeS. A., GrossJ. J., & GabrieliJ. D. E. (2002). Rethinking feelings: An fMRI study of the cognitive regulation of emotion. Journal of Cognitive Neuroscience, 14, 12151229.
OlsavskyA. K., TelzerE. H., ShapiroM., HumphreysK. L., FlanneryJ., GoffB., & TottenhamN. (2013). Indiscriminate amygdala response to mothers and strangers after early maternal deprivation. Biological Psychiatry, 74, 853860.
PerlmanS. B., & PelphreyK. A. (2011). Developing connections for affective regulation: Age-related changes in emotional brain connectivity. Journal of Experimental Child Psychology, 108, 607620.
PhanK. L., FitzgeraldD. A., NathanP. J., MooreG. J., UhdeT. W., & TancerM. E. (2005). Neural substrates for voluntary suppression of negative affect: A functional magnetic resonance imaging study. Biological Psychiatry, 57, 210219.
PhelpsE. A., & LeDouxJ. E. (2005). Contributions of the amygdala to emotion processing: From animal models to human behavior. Neuron, 48, 175187.
PhilipN. S., SweetL. H., TyrkaA. R., PriceL. H., BloomR. F., & CarpenterL. L. (2013). Decreased default network connectivity is associated with early life stress in medication-free healthy adults. European Neuropsychopharmacology, 23, 2432.
PowerJ. D., BarnesK. A., SnyderA. Z., SchlaggarB. L., & PetersenS. E. (2012). Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. NeuroImage, 59, 21422154.
QuirogaA., WillisG. B., Lopez-RodriguezL., & MorenoA. (2015). Psychological consequences of collective violence in childhood: The case of Monterrey, Mexico. Estudios De Psicologia, 36, 294315.
RijlaarsdamJ., StevensG. W. J. M., van der EndeJ., HofmanA., JaddoeV. W. V., MackenbachJ. P., … TiemeierH. (2013). Economic disadvantage and young children's emotional and behavioral problems: Mechanisms of risk. Journal of Abnormal Child Psychology, 41, 125137.
Salimi-KhorshidiG., DouaudG., BeckmannC. F., GlasserM. F., GriffantiL., & SmithS. M. (2014). Automatic denoising of functional MRI data: Combining independent component analysis and hierarchical fusion of classifiers. NeuroImage, 15, 449468.
SanchezC. E., RichardsJ. E., & AlmliC. R. (2012). Age-specific MRI templates for pediatric neuroimaging. Developmental Neuropsychology, 37, 379399.
SatterthwaiteT. D., WolfD. H., LougheadJ., RuparelK., ElliottM. A., HakonarsonH., GurR. C., & GurR. E. (2012). Impact of in-scanner head motion on multiple measures of functional connectivity: Relevance for studies of neurodevelopment in youth. NeuroImage, 60, 623632.
ShawP., GreensteinD., LerchJ., ClasenL., LenrootR., GogtayN., … GieddJ. (2006). Intellectual ability and cortical development in children and adolescents. Nature, 440, 676679.
ShawP., KabaniN. J., LerchJ. P., EckstrandK., LenrootR., GogtayN., … WiseS. P. (2008). Neurodevelopmental trajectories of the human cerebral cortex. Journal of Neuroscience, 28, 35863594.
SroufeL. A. (1990). Considering normal and abnormal together: The essence of developmental psychopathology. Development and Psychopathology, 2, 335347.
TellegenP. J., WinkelM., Wijnberg-WilliamsB., & LarosJ. A. (2005). Snijders-Oomen Niet-Verbale Intelligentietest: SON-R 2 1/2−7. Amsterdam: Boom Testuitgevers.
TiemeierH., VeldersF. P., SzekelyE., RozaS. J., DielemanG., JaddoeV. W., … VerhulstF. C. (2012). The Generation R Study: A review of design, findings to date, and a study of the 5-HTTLPR by environmental interaction from fetal life onward. Journal of the American Academy of Child & Adolescent Psychiatry, 51, 11191135.
TottenhamN. (2015). Social scaffolding of human amygdala–mPFC circuit development. Social Neuroscience, 10, 489499.
TottenhamN., HareT. A., QuinnB. T., McCarryT. W., NurseM., GilhoolyT., … CaseyB. J. (2010). Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulation. Developmental Science, 13, 4661.
TownsendJ. D., TorrisiS. J., LiebermanM. D., SugarC. A., BookheimerS. Y., & AltshulerL. L. (2013). Frontal-amygdala connectivity alterations during emotion downregulation in bipolar I disorder. Biological Psychiatry, 73, 127135.
van der VoortA., LintingM., JufferF., Bakermans-KranenburgM. J., SchoenmakerC., & van IJzendoornM. H. (2014). The development of adolescents’ internalizing behavior: Longitudinal effects of maternal sensitivity and child inhibition. Journal of Youth Adolescence, 43, 528540.
van IJzendoornM. H., JufferF., & PoelhuisC. W. (2005). Adoption and cognitive development: A meta-analytic comparison of adopted and nonadopted children's IQ and school performance. Psychological Bulletin, 131, 301316.
WhiteT., El MarrounH., NijsI., SchmidtM., van der LugtA., WielopolkiP. A., … VerhulstF. C. (2013). Pediatric population-based neuroimaging and the Generation R Study: The intersection of developmental neuroscience and epidemiology. European Journal of Epidemiology, 28, 99111.
WhiteT., MuetzelR., SchmidtM., LangeslagS. J., JaddoeV., HofmanA., … TiemeierH. (2014). Time of acquisition and network stability in pediatric resting-state functional magnetic resonance imaging. Brain Connectivity, 4, 417427.
WhittleS., SimmonsJ. G., DennisonM., VijayakumarN., SchwartzO., YapM. B. H., … AllenN. B. (2014). Positive parenting predicts the development of adolescent brain structure: A longitudinal study. Developmental Cognitive Neuroscience, 8, 717.
WhittleS., YapM. B. H., YucelM., SheeberL., SimmonsJ. G., PantelisC., & AllenN. B. (2009). Maternal responses to adolescent positive affect are associated with adolescents’ reward neuroanatomy. Social Cognitive and Affective Neuroscience, 4, 247256.
WuR. Y., SongZ. Z., WangS. Y., ShuiL., TaiF. D., QiaoX. F., & HeF. Q. (2014). Early paternal deprivation alters levels of hippocarnpal brain-derived neurotrophic factor and glucocorticold receptor and serum corticosterone and adrenocorticotropin in a sex-specific way in socially monogamous mandarin voles. Neuroendocrinology, 100, 119128.
YuP., AnS. C., TaiF. D., ZhangX., HeF. Q., WangJ. L., … WuR. Y. (2012). The effects of neonatal paternal deprivation on pair bonding, NAcc dopamine receptor mRNA expression and serum corticosterone in mandarin voles. Hormones and Behavior, 61, 669677.
ZimmermannP., & IwanskiA. (2014). Emotion regulation from early adolescence to emerging adulthood and middle adulthood: Age differences, gender differences, and emotion-specific developmental variations. International Journal of Behavioral Development, 38, 182194.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Development and Psychopathology
  • ISSN: 0954-5794
  • EISSN: 1469-2198
  • URL: /core/journals/development-and-psychopathology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Full text views

Total number of HTML views: 20
Total number of PDF views: 160 *
Loading metrics...

Abstract views

Total abstract views: 821 *
Loading metrics...

* Views captured on Cambridge Core between 12th April 2017 - 20th October 2017. This data will be updated every 24 hours.