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Cited by 91Neuroendocrine regulation and behaviorFunctional Brain Connectivity StudiesNeurotransmitter Receptor Influence on Behavior

Oxytocin effects on complex brain networks are moderated by experiences of maternal love withdrawal

Open access
Riem, Madelon M.E., van IJzendoorn, Marinus H., Tops, Mattie, Boksem, Maarten A.S., Rombouts, Serge A.R.B., Bakermans-Kranenburg, Marian J.·2013·European Neuropsychopharmacology
DOI 10.1016/j.euroneuro.2013.01.011
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Abstract

The neuropeptide oxytocin has been implicated in a variety of social processes. However, recent studies indicate that oxytocin does not enhance prosocial behavior in all people in all circumstances. Here, we investigate effects of intranasal oxytocin administration on intrinsic functional brain connectivity with resting state functional magnetic resonance imaging. Participants were 42 women who received a nasal spray containing either 16 IU of oxytocin or a placebo and reported how often their mother used love withdrawal as a disciplinary strategy involving withholding love and affection after a failure or misbehavior. We found that oxytocin changes functional connectivity between the posterior cingulate cortex (PCC) and the brainstem. In the oxytocin group there was a positive connectivity between these regions, whereas the placebo group showed negative connectivity. In addition, oxytocin induced functional connectivity changes between the PCC, the cerebellum and the postcentral gyrus, but only for those participants who experienced low levels of maternal love withdrawal. We speculate that oxytocin enhances prosocial behavior by influencing complex brain networks involved in self-referential processing and affectionate touch, most prominently in individuals with supportive family backgrounds.

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Written from the paper’s full text.

TL;DR

Intranasal oxytocin altered resting-state functional connectivity of the posterior cingulate cortex (PCC) in women, especially PCC-brainstem connectivity. Oxytocin-induced changes in PCC-cerebellum and PCC-postcentral gyrus connectivity were moderated by maternal love withdrawal, appearing only in women reporting low love withdrawal.

Key findings

  • Oxytocin changed PCC-brainstem and PCC-cerebellum connectivity: the oxytocin group showed positive PCC-brainstem/PCC-cerebellum connectivity, whereas the placebo group showed negative connectivity (between-group cluster size = 745 voxels, peak Z = 3.97, MNI coordinates −8, −6, −34).
  • For PCC-cerebellum connectivity, the condition × love withdrawal interaction was significant (β = 0.38, p = 0.01; model F(3,38) = 3.89, p = 0.02). Oxytocin changed PCC-cerebellum connectivity in participants with low love withdrawal (t(38) = 2.80, p = 0.01, Cohen’s d = 1.49) but not in those with high love withdrawal (t(38) = −0.25, p = 0.81, Cohen’s d = −0.09).
  • For PCC-brainstem connectivity, the effect of condition was significant (β = −0.38, p = 0.01), with no love withdrawal effect (β = −0.07, p = 0.63) and no significant interaction (β = 0.21, p = 0.17).
  • In a supplementary whole-brain analysis of participants reporting low love withdrawal, oxytocin also induced PCC-brainstem/cerebellum changes (cluster size = 689 voxels, peak Z = 3.94) and PCC-postcentral gyrus changes (cluster size = 581 voxels, peak Z = 4.11). Amygdala and insula seed analyses showed no significant group differences.

Methods

  • Double-blind, placebo-controlled intranasal oxytocin study in 42 women (mean age 28.98 years, SD = 7.48, range 22–49; 71.4% used oral contraceptives), recruited from monozygotic and dizygotic twin pairs without children. One sibling per twin pair was randomly assigned to oxytocin (16 IU nasal spray) and the other to placebo (NaCl); scanning occurred approximately 35 min after administration.
  • Resting-state fMRI was acquired on a 3-T Philips Achieva system (170 whole-brain EPIs; TR = 2.2 s; TE = 30 ms). Seed-based functional connectivity analyses used the amygdala, insula, and PCC as seeds in FSL FEAT, with age, menstrual cycle phase, and oral contraceptive use as confound regressors; statistical images were thresholded at Z > 2.3 with cluster-corrected p < 0.05.
  • Maternal love withdrawal was measured with an 11-item questionnaire (Cronbach’s α = 0.85; mean item score = 2.15, SD = 0.71). Hierarchical regression tested condition, love withdrawal, and their interaction predicting PCC-brainstem and PCC-cerebellum connectivity; two outlying PCC-cerebellum values were winsorized.

Limitations

  • The paper states that the between-subject design carries a risk of pre-existing differences between oxytocin and placebo groups, although most participants were twin pairs matched on age and rearing experiences, and monozygotic twins also matched on genotype.
  • The paper notes limitations including self-reported maternal love withdrawal, inability to determine directionality of PCC-cerebellum-brainstem relations, focus on three seed regions to the whole brain rather than other region-to-region interactions, and generalizability only to women without parenting experience.
  • The text also makes evident that the sample was restricted to right-handed women without children and that oxytocin may have different functional connectivity effects in men and women.

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Crossref · 10.1016/j.euroneuro.2013.01.011

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Claims the paper makes

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  • Findingown data

    Oxytocin significantly changed PCC-cerebellum connectivity in participants with low love withdrawal scores.

    “A priori contrasts showed that oxytocin significantly changed PCC-cerebellum connectivity in participants with low love withdrawal scores (t(38)=2.80,p=0.01,Cohen's d=1.49), but oxytocin did not have a significant effect in participants reporting high love withdrawal (t(38)=À0.25,p=0.81,Cohen's d=À0.09),see Figure 3.”
    Quote in the paperSubstantial claim
  • Findingown data

    Oxytocin administration induced a significant change in resting-state functional connectivity between the PCC and the brainstem in women.

    “The between-group comparison (Oxytocin4Placebo) showed that oxytocin significantly induced connectivity changes between the PCC, the brainstem and the cerebellum (1 Cluster, size= 745 voxels, peak Z= 3.97, MNI coordinates x,y,z (mm) =À8, À6, À34) (see Figure 2).”
    • Also stated in: § Abstract · plain
      “We found that oxytocin changes functional connectivity between the posterior cingulate cortex (PCC) and the brainstem.”
    Quote in the paperSubstantial claim
  • Findingown data

    The interaction between condition (oxytocin vs placebo) and experienced love withdrawal significantly predicted PCC-cerebellum connectivity.

    “The interaction between condition and love withdrawal significantly predicted PCC-cerebellum connectivity (ß=0.38,p=0.01).”
    Quote in the paperSubstantial claim
  • Findingown data

    Oxytocin did not have a significant effect on PCC-cerebellum connectivity in participants reporting high love withdrawal.

    “A priori contrasts showed that oxytocin significantly changed PCC-cerebellum connectivity in participants with low love withdrawal scores (t(38)=2.80,p=0.01,Cohen's d=1.49), but oxytocin did not have a significant effect in participants reporting high love withdrawal (t(38)=À0.25,p=0.81,Cohen's d=À0.09),see Figure 3.”
    Quote in the paperSubstantial claim
  • Findingown data

    Intranasal oxytocin changes PCC connectivity.

    “Our finding that intranasal oxytocin changes PCC connectivity is in line with a previous study in which we found that oxytocin increased connectivity between the amygdala and the PCC and other emotional brain regions during exposure to infant laughter (Riem et al., 2012).”
    Quote in the paperSubstantial claim
  • May combine two claims. 18
  • Classified as probably not a substantial claim. 60

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    Findingown data

    In the oxytocin group there was positive connectivity between the PCC and the brainstem, whereas the placebo group showed negative connectivity between these regions.

    “In the oxytocin group there was a positive connectivity between these regions, whereas the placebo group showed negative connectivity.”
    • Also stated in: § 3. Results · plain
      “Inspection of the group means revealed that there was a positive connectivity between the PCC and the cerebellum and between the PCC and the brainstem in the oxytocin group and negative connectivities between these regions in the placebo group (see Figure 2), indicating that oxytocin changed PCC-brainstem and PCC-cerebellum connectivity.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    In a supplementary analysis of participants reporting low love withdrawal, oxytocin significantly induced connectivity changes between the PCC and the postcentral gyrus.

    “In addition, oxytocin significantly induced connectivity changes between the PCC and the postcentral gyrus (Cluster size =581 voxels, peak Z =4.11, MNI coordinates x,y,z (mm) =À8, À44, 60) (see Figure s1 in Supporting Information).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Love withdrawal has been associated with low self-esteem and low emotional well-being.

    “It has been associated with low self-esteem and low emotional well-being and has been found to moderate the positive effect of oxytocin on prosocial behavior (Van IJzendoorn et al., 2011).”
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    Spontaneous BOLD fluctuations are not random noise, but specifically organized in the resting human brain.

    “Over the last decade many studies have found that spontaneous BOLD fluctuations are not random noise, but specifically organized in the resting human brain (Biswal et al., 2010).”
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    The degree of correlation in resting state networks has been shown to be related to behavioral outcomes.

    “Activity in the different resting state networks has been linked to different functions (Laird et al., 2011) and the degree of correlation has been shown to be related to behavioral outcomes (Vincent et al., 2006) and clinical conditions (Greichius, 2008).”
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    Activity in different resting state networks has been linked to different functions.

    “Activity in the different resting state networks has been linked to different functions (Laird et al., 2011) and the degree of correlation has been shown to be related to behavioral outcomes (Vincent et al., 2006) and clinical conditions (Greichius, 2008).”
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    Recent studies indicate that the beneficial effects of oxytocin are more nuanced than previously thought.

    “However, recent studies indicate that the beneficial effects of oxytocin are more nuanced than previously thought (Bartz et al., 2010;De Dreu et al., 2010;Van IJzendoorn et al., 2011).”
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    Oxytocin has been shown to stimulate a range of social behaviors.

    “The neuropeptide oxytocin has been shown to stimulate a range of social behaviors (for a review see Bartz et al. (2011)).”
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    Premisecitation

    Contextual and individual differences seem to moderate oxytocin effects on social behavior and cognition.

    “Contextual and individual differences seem to moderate oxytocin effects on social behavior and cognition (Bartz et al., 2011).”
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    Regions that are functionally related tend to be highly correlated in their spontaneous BOLD activity during rest.

    “Regions that are functionally related tend to be highly correlated in their spontaneous BOLD activity during rest (Fox et al., 2007).”
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    The cerebellum is more dependent upon environmental factors than most other brain regions.

    “In addition, harsh caregiving experiences have been shown to affect the maturation of the cerebellum (Bauer et al., 2009), a brain region that is more dependent upon environmental factors than most other brain regions (Giedd et al., 2007).”
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    Oxytocin increases defensive reactions to out-group members.

    “De Dreu et al. (2010) showed that oxytocin increases in-group altruism, but also increases defensive reactions to out-group members.”
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    Different drugs produce specific and detectable changes in resting state networks.

    “In addition, it has been shown that different drugs produce specific and detectable changes in these resting state networks (Khalili-Mahani et al., 2012).”
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    Oxytocin increases in-group altruism.

    “De Dreu et al. (2010) showed that oxytocin increases in-group altruism, but also increases defensive reactions to out-group members.”
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    Premisecitation

    The amygdala is part of a neural network involved in emotion processing and is strongly connected to the precuneus/PCC, OFC, ACC and brainstem.

    “The amygdala is part of a neural network involved in emotion processing and is strongly connected to other brain regions such as the precuneus/posterior cingulate cortex (PCC), the orbitofrontal cortex (OFC), the anterior cingulate (ACC) and the brainstem (Bos et al., 2012;Pessoa, 2008).”
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    The degree of correlation in resting state networks has been shown to be related to clinical conditions.

    “Activity in the different resting state networks has been linked to different functions (Laird et al., 2011) and the degree of correlation has been shown to be related to behavioral outcomes (Vincent et al., 2006) and clinical conditions (Greichius, 2008).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Greichius, 2008 source

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    Premisecitation

    Harsh caregiving experiences have been shown to affect the maturation of the cerebellum.

    “In addition, harsh caregiving experiences have been shown to affect the maturation of the cerebellum (Bauer et al., 2009), a brain region that is more dependent upon environmental factors than most other brain regions (Giedd et al., 2007).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Bauer et al., 2009 source

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    Premisecitation

    Oxytocin administration increased participants' willingness to donate money only in participants who experienced low levels of parental love withdrawal, without such effect in participants who experienced high levels of parental love withdrawal.

    “For example, Van IJzendoorn et al. (2011) found that oxytocin administration increased participants' willingness to donate money but only in participants who experienced low levels of parental love withdrawal, without such effect in participants who experienced high levels of parental love withdrawal.”
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    Premisecitation

    Parental use of love-withdrawal has been associated with high concern over mistakes and low emotional well-being.

    “Parental use of love-withdrawal has been associated with high concern over mistakes and low emotional well-being (Elliot and Thrash, 2004;Renk et al., 2006).”
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    Excessive use of love withdrawal is considered psychological maltreatment.

    “Excessive use of love withdrawal is considered psychological maltreatment (Euser et al., 2010) and has great impact on neurobiological development.”
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    Interpretationcitation

    Resting state fMRI could be useful for 'finger-printing' different pharmacological agents within the same individual's brain.

    “This indicates that resting state fMRI could be useful for ''finger-printing'' different pharmacological agents within the same individual's brain (Khalili-Mahani et al., 2012) as well as for studying differential pharmacological effects in individuals with different backgrounds.”
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    Premisecitation

    Recent intranasal oxytocin administration experiments have shown that oxytocin stimulates a range of other social behaviors.

    “Recent intranasal oxytocin administration experiments have shown that oxytocin stimulates sensitive parenting (Naber et al., 2010) and a range of other social behaviors (for a review see Bartz et al. (2011)).”
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    Premisecitation

    Connectivity within this neural network can be enhanced by intranasal oxytocin.

    “Consistent with other studies (Bos et al., 2012) a previous study showed that connectivity within this neural network can be enhanced by intranasal oxytocin (Riem et al., 2012), which in turn facilitates the integration of emotion and cognition and the evaluation of emotional signals (Pessoa, 2008).”
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    Premisecitation

    In individuals who experienced negative caregiving experiences, the prosocial effects of oxytocin are hindered but not altered.

    “Not all studies find these polarizing oxytocin effects; some indicate that the prosocial effects of oxytocin are hindered but not altered in individuals who experienced negative caregiving experiences (Meinlschmidt and Heim, 2007).”
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    The neuropeptide oxytocin plays a central role in attachment formation, affiliation and social behavior.

    “The neuropeptide oxytocin plays a central role in attachment formation, affiliation and social behavior (Carter, 1998).”
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    Premisecitation

    Recent intranasal oxytocin administration experiments have shown that oxytocin stimulates sensitive parenting.

    “Recent intranasal oxytocin administration experiments have shown that oxytocin stimulates sensitive parenting (Naber et al., 2010) and a range of other social behaviors (for a review see Bartz et al. (2011)).”
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    Premisecitation

    Oxytocin decreases amygdala activation during the perception of fear-inducing or aversive social stimuli.

    “Oxytocin decreases amygdala activation during the perception of fear-inducing or aversive social stimuli; it has been suggested that this explains the stress-reducing effects of oxytocin (Gamer et al., 2010;Riem et al., 2011).”
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    Premisecitation

    Oxytocin increases activation in brain regions important for emotional processing, including the insula and inferior frontal gyrus during the perception of social stimuli.

    “Some studies showed that oxytocin increases activation in brain regions important for emotional processing, including the insula and inferior frontal gryus during the perception of social stimuli (Riem et al., 2011).”
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    Premisecitation

    The PCC is a functional connectivity hub because of its high degree of connectivity with other brain regions.

    “The PCC is considered a functional connectivity hub because of its high degree of connectivity with other brain regions (Buckner et al., 2009).”
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    Study design and conductcitation

    The 11-item questionnaire on maternal use of love withdrawal has been used previously.

    “The 11-item questionnaire has been used previously (Van IJzendoorn et al., 2011).”
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    Study design and conductnone given

    One sibling from each twin pair was randomly assigned to the oxytocin condition and the other sibling to the placebo condition.

    “One sibling from each twin pair (9 MZ pairs, 7 DZ pairs) was randomly assigned to the oxytocin condition and the other sibling to the placebo condition, resulting in a group of 22 participants who were administered oxytocin and a group of 20 participants who were administered a placebo.”
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    Premisecitation

    Oxytocin increased connectivity between the amygdala and the PCC and other emotional brain regions during exposure to infant laughter.

    “in which we found that oxytocin increased connectivity between the amygdala and the PCC and other emotional brain regions during exposure to infant laughter (Riem et al., 2012).”
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    Sripada et al. (2013) found intranasal oxytocin effects on resting state functional connectivity in males.

    “Sripada et al. (2013) found intranasal oxytocin effects on resting state functional connectivity in males.”
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    Premisecitation

    Children who experienced early severe neglect did not show a change in oxytocin levels after physical contact with their mother, whereas oxytocin levels increased in children reared in a loving family.

    “In a previous study children who experienced early severe neglect did not show a change in oxytocin levels after physical contact with their mother, whereas oxytocin levels were increased in children who were reared in a loving family (Fries et al., 2005).”
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    Premisecitation

    Enhanced connectivity within this neural network facilitates the integration of emotion and cognition and the evaluation of emotional signals.

    “Consistent with other studies (Bos et al., 2012) a previous study showed that connectivity within this neural network can be enhanced by intranasal oxytocin (Riem et al., 2012), which in turn facilitates the integration of emotion and cognition and the evaluation of emotional signals (Pessoa, 2008).”
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    Study design and conductown data

    Participants received a nasal spray containing either 16 IU of oxytocin or a placebo.

    “Participants were 42 women who received a nasal spray containing either 16 IU of oxytocin or a placebo and reported how often their mother used love withdrawal as a disciplinary strategy involving withholding love and affection after a failure or misbehavior.”
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    Premisecitation

    The precuneus/PCC is the main functional connectivity hub in the resting brain.

    “In addition, the precuneus/posterior cingulate cortex (PCC), the main functional connectivity hub in the resting brain (Buckner et al., 2009), was selected as seed region (center voxel =À2, À50, 36, see Supporting Information).”
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    Study design and conductnone given

    Drug administration was double-blind.

    “Drug administration was double-blind.”
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    Study design and conductcitation

    The CSF signal and the global signal were added as regressors to the model in order to reduce the influence of artifacts caused by physiological signal sources on the results.

    “In addition, the CSF signal and the global signal were added as regressors to the model in order to reduce the influence of artifacts caused by physiological signal sources on the results (Fox et al., 2007).”
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    Motion parameters were added to each model.

    “Motion parameters were added to each model.”
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    Study design and conductnone given

    The statistical images were thresholded using clusters determined by Z>2.3 and a cluster corrected significance threshold of p<0.05.

    “The statistical images were thresholded using clusters determined by Z42.3 and a cluster corrected significance threshold of po0.05.”
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    Study design and conductcitation

    Two outlying values for PCC-cerebellum connectivity were winsorized to reduce any influence of extreme scores.

    “Two outlying values for PCC-cerebellum connectivity were winsorized to reduce any influence of extreme scores (Tabachnik and Fidell, 2001).”
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    Age, menstrual cycle and use of oral contraceptives were included as confound regressors in the model in all analyses.

    “We included age, menstrual cycle (follicular or luteal phase) and use of oral contraceptives as confound regressors in the model in all analyses.”
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    Study design and conductown data

    Cronbach's alpha for the love withdrawal questionnaire was 0.85 in the current sample.

    “Cronbach's alpha was 0.85 in the current sample.”
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    Study design and conductown data

    Participants were screened for psychiatric or neurological disorders and alcohol and drug use.

    “A group of 44 right-handed females who met inclusion criteria and were willing to participate were recruited, 21 from MZ twin pairs and 23 from DZ twin pairs, without children of their own, in good health, without hearing impairments and MRI contraindications, pregnancy, and screened for psychiatric or neurological disorders and alcohol and drug use.”
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    Premisecitation

    The cerebellum is one of the least heritable brain structures and is more influenced by environmental factors during development than other brain regions.

    “The cerebellum is one of the least heritable brain structures and is more influenced by environmental factors during development than other brain regions (Giedd et al., 2007).”
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    Enhanced PCC connectivity during rest may represent an increase in ongoing self-referential processes such as self-consciousness, sense of agency, and self-reflection.

    “Enhanced PCC connectivity during rest may represent an increase in ongoing self-referential processes such as self-consciousness, sense of agency, and selfreflection (Cavanna, 2007;Cavanna et al., 2006).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Cavanna, 2007 source

      Not checked in the free run.

    • cites Cavanna et al., 2006 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The absence of significant oxytocin effects on amygdala-brainstem connectivity may be because fearful stimuli were not used.

    “However, in this study we did not find significant oxytocin effects on amygdala-brainstem connectivity, perhaps because we did not use fearful stimuli.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    According to simulation theory, individuals use self-reflection to understand the mental states of others.

    “According to simulation theory individuals use self-reflection to understand the mental states of others (Goldman, 1992).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Goldman, 1992 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The results are consistent with research showing that oxytocin is crucially involved in social cognition and affiliation.

    “Our results are consistent with research showing that oxytocin is crucially involved in social cognition and affiliation and provide more insight into the neural mechanism underlying the beneficial effects of oxytocin.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    The PCC and other regions in the default mode network are of great importance for social cognition.

    “Therefore, the PCC and other regions in the default mode network have been suggested to be of great importance for social cognition (Schilbach et al., 2008).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Schilbach et al., 2008 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The cerebellum plays an important role in emotion and cognition.

    “However, many studies indicate that it also plays an important role in emotion and cognition (Schmahmann, 2010).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Schmahmann, 2010 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The PCC plays a role in understanding other people's minds.

    “This suggestion is supported by studies pointing to a role of the PCC in understanding other people's minds (e.g.Wolf et al., 2010).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Wolf et al., 2010 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    PCC-cerebellum connectivity is altered in patients with depression, which could represent heightened rumination during resting state.

    “Alalade et al. (2011) showed that PCC-cerebellum connectivity (in a subregion of the cerebellum that was different from the significantly activated region of the cerebellum in the current study) is altered in patients with depression, and suggested that this could represent heightened rumination during resting state.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Alalade et al., 2011 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing).

    Premisecitation

    Decreased amygdala activation might be the underlying neural mechanism of the anxiolytic effects of oxytocin.

    “Because projections between the amygdala and brainstem are involved in fear behavior and arousal (LeDoux, 2000) it has been suggested that decreased amygdala activation might be the underlying neural mechanism of the anxiolytic effects of oxytocin (Gamer et al., 2010;Riem et al., 2011).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Gamer et al., 2010 source

      Not checked in the free run.

    • cites Riem et al., 2011 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Children who experienced early deprivation had smaller superiorposterior cerebellar lobe volumes than a control group.

    “This is in line with Bauer et al.'s (2009) study showing that children who experienced early deprivation had smaller superiorposterior cerebellar lobe volumes than a control group.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Bauer et al., 2009 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Impaired PCC-brainstem coupling has been found in persistent vegetative state, indicating that connectivity between these regions plays a role in consciousness.

    “Impaired PCCbrainstem coupling has been found in persistent vegetative state (Silva et al., 2010), indicating that connectivity between these regions plays a role in consciousness.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Silva et al., 2010 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The cerebellum is connected with the dorsolateral prefrontal cortex, the PCC, the amygdala, the inferior parietal lobule and the brainstem, and these connectivities are important for cognition and emotion.

    “The cerebellum is connected with the dorsolateral prefrontal cortex, the PCC, the amygdala, the inferior parietal lobule and the brainstem (Heath and Harper, 1974;O'Reilly et al., 2010;Strick et al., 2009) and studies have shown that these connectivities are important for cognition and emotion.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Heath and Harper, 1974

      Not checked in the free run.

    • cites O'Reilly et al., 2010 source

      Not checked in the free run.

    • cites Strick et al., 2009 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Intranasal oxytocin administration decreased functional connectivity between the amygdala and the brainstem during exposure to fearful social faces.

    “More specific, intranasal oxytocin administration decreased functional connectivity between the amygdala and the brainstem during exposure to fearful social faces (Kirsch et al., 2005).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kirsch et al., 2005 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Oxytocin levels are positively related with parent-infant contact and warm touch in married couples.

    “The oxytocin effects on increased functional connectivity between the PCC and the postcentral gyrus for individuals who experienced low levels of love withdrawal is consistent with studies showing that oxytocin levels are positively related with parent-infant contact and warm touch in married couples (Feldman et al., 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Feldman et al., 2010 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The postcentral gyrus is part of a somatosensory brain network that has been associated with the experience of pleasant and human touch.

    “The postcentral gyrus is part of a somatosensory brain network (Tomasi and Volkow, 2011) that has been associated with the experience of pleasant and human touch (McCabe et al., 2008).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Tomasi and Volkow, 2011

      Not checked in the free run.

    • cites McCabe et al., 2008 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    A limitation of the study is the use of self-reported maternal love withdrawal.

    “A limitation of our study is the use of self-reported maternal love withdrawal.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    The study focused on functional connectivity between three regions of interest and the entire brain, and therefore does not allow conclusions on other region-to-region interactions.

    “In addition, we focused on functional connectivity between three regions of interest and the entire brain.Therefore our study does not allow conclusions on other region-to-region interactions.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Oxytocin has an important role in initiating the ''touch circuitry'' between parents and infants in the first months of parenthood.

    “This is convergent with studies showing that oxytocin has an important role in initiating the ''touch circuitry'' between parents and infants in the first months of parenthood (Feldman et al., 2010) and with studies showing that this circuitry is disrupted in children who experienced early neglect (Fries et al., 2005).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Feldman et al., 2010 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductnone given

    Most participants were monozygotic and dizygotic twin pairs, perfectly matched on age and global child-rearing experiences and even on genotype in MZ twin pairs.

    “However, most of our participants were monozygotic (MZ) and dizygotic (DZ) twin pairs, perfectly matched on age and global child-rearing experiences and even on genotype in MZ twin pairs.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Sripada et al. (2013) found that intranasal oxytocin increased connectivity between the amygdala and rostral medial frontal cortex in males, but had no effects on coupling between other brain regions.

    “Sripada et al. (2013) examined the effects of intranasal oxytocin on functional resting-state connectivity in males and found increased connectivity between the amygdala and rostral medial frontal cortex, but no effects on coupling between other brain regions.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Sripada et al., 2013

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Intranasal oxytocin leads to more efficient processing of touch-related information, but only in individuals with supportive family backgrounds.

    “Our finding suggests that intranasal oxytocin leads to more efficient processing of touch-related information, but only in individuals with supportive family backgrounds.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Self-reported maternal love withdrawal validly reflects participants' experiences of maternal love withdrawal.

  • May combine two claims.

    Study design and conductreasoning

    The study used a between-subject design, which implies the risk of pre-existing differences between the oxytocin and placebo group.

    “We used a betweensubject design which implies the risk of pre-existing differences between the oxytocin and placebo group.”
    Quote in the paperNot a substantial claim
68 of 68

  • The paper relies on this without support.

    It is as yet unknown whether oxytocin affects functional brain connectivity in a 'taskfree' setting in females.

    “It is as yet unknown whether oxytocin affects functional brain connectivity in a 'taskfree' setting in females.”

  • The paper relies on this without support.

    To our knowledge this is the first randomized controlled trial examining the neural mechanism underlying differential oxytocin effects with task-free techniques of functional brain networks in women.

    “To our knowledge this is the first randomized controlled trial examining the neural mechanism underlying differential oxytocin effects with task-free techniques of functional brain networks in women.”

  • The paper relies on this without support.

    Self-reported maternal love withdrawal validly reflects participants' experiences of maternal love withdrawal.

    “A limitation of our study is the use of self-reported maternal love withdrawal.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • An enhanced PCC activation under OXT may indicate an increased processing of positive self-reflection and touch-related information.

    “Our results thus support the idea that an enhanced PCC activation under OXT may indicate an increased processing of positive self-reflection and touch-related information”

    From An oxytocin-induced facilitation of neural and emotional responses to social touch correlates inversely with autism traits (2014) · cites this paper as Riem et al, 2013

  • Among non-parent women, administration of OT was associated with reduced responses in the amygdala to negative emotional images that were stressful, as well as stimuli that depict infants either crying or laughing.

    “Among non-parent women, administration of OT was associated with reduced responses in the amygdala to negative emotional images that were stressful (Rupp et al., 2012), as well as stimuli that depict infants either crying (Riem et al., 2011) or laughing (Riem et al., 2013).”

    From The maternal brain and its plasticity in humans (2016) · cites this paper as Riem et al., 2013

  • In these studies, administration of OT was associated with increased activations in areas related to regulation of emotion and empathy, including the ACC, the OFC, and insula.

    “In fact, in these studies, administration of OT was associated with increased activations in areas related to regulation of emotion and empathy, including the ACC, the OFC, and insula (Riem et al., 2011; Riem et al., 2013).”

    From The maternal brain and its plasticity in humans (2016) · cites this paper as Riem et al., 2013

  • Factors such as gender, attachment style, and early parental experiences appear to moderate the effects of intranasal oxytocin on several outcome measures.

    “Factors such as gender [48], attachment style [49], and early parental experiences [50] appear to moderate the effects of intranasal oxytocin on several outcome measures [51,52].”

    From Efficacy of oxytocin administration early after psychotrauma in preventing the development of PTSD: study protocol of a randomized controlled trial (2014) · cites this paper as [50]

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • ConsistentF(3, 38) = 3.89reported p = .02 · recomputed p = .016

    “F(3,38)=3.89,p = .02”

  • Consistentt(38) = 2.8reported p = .01 · recomputed p = .008

    “t(38)=2.80,p = .01”

  • Consistentt(38) = -0.25reported p = .81 · recomputed p = .804

    “t(38)=À0.25,p = .81”

  • ConsistentF(3, 38) = 3.15reported p = .04 · recomputed p = .036

    “F(3,38)=3.15,p = .04”

4 of 4

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Self-check results appear here once an independent check has confirmed them.

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Authors
Riem, M. M. E., van IJzendoorn, M. H., Tops, M., Boksem, M. A. S., Rombouts, S. A. R. B., & Bakermans-Kranenburg, M. J.
Affiliations
  • Leiden University (NL)
  • Radboud University Nijmegen (NL)
ORCID
Venue
European Neuropsychopharmacology
Publisher
Elsevier BV
Published
2013-10
Volume
23
Issue
10
Pages
1288-1295
ISSN
0924-977X (ISSN-L)
DOI
10.1016/j.euroneuro.2013.01.011
OpenAlex
W2051332633
Semantic Scholar
bdc971a10d7084ef9844362b8178dc3d734b9288
Cited by
91
References
50
Citations by year
2026: 3 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 9 · 2019: 12 · 2018: 8 · 2017: 8 · 2016: 7 · 2015: 9 · 2014: 12 · 2013: 7 · 2012: 1
FWCI
17.46
Type
journal article
Language
en
Open access
Licence
Locations
  • European Neuropsychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
  • VU Research Portal (publishedVersion, other-oa)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Leiden Repository (Leiden University) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
oxytocin, functional connectivity, posterior cingulate cortex, brainstem, cerebellum, postcentral gyrus, prosocial behavior, self-referential processing, affectionate touch, family background, intranasal administration
MeSH terms
Administration, Intranasal, Adult, Brain, Brain Stem, Cerebellum, Child, Child Development, Female, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Maternal Behavior, Maternal Deprivation, Middle Aged, Mother-Child Relations, Nerve Net, Netherlands, Oxytocin, Social Support, Neurogenesis, Young Adult, Functional Neuroimaging

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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