Intranasal oxytocin enhances connectivity in the neural circuitry supporting social motivation and social perception in children with autism
Open accessAbstract
Oxytocin (OT) has become a focus in investigations of autism spectrum disorder (ASD). The social deficits that characterize ASD may relate to reduced connectivity between brain sites on the mesolimbic reward pathway (nucleus accumbens; amygdala) that receive OT projections and contribute to social motivation, and cortical sites involved in social perception. Using functional magnetic resonance imaging and a randomized, double blind, placebo-controlled crossover design, we show that OT administration in ASD increases activity in brain regions important for perceiving social-emotional information. Further, OT enhances connectivity between nodes of the brain’s reward and socioemotional processing systems, and does so preferentially for social (versus nonsocial) stimuli. This effect is observed both while viewing coherent versus scrambled biological motion, and while listening to happy versus angry voices. Our findings suggest a mechanism by which intranasal OT may bolster social motivation—one that could, in future, be harnessed to augment behavioral treatments for ASD.
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Written from the paper’s full text.
TL;DR
In a randomized, double-blind, placebo-controlled crossover fMRI study, intranasal oxytocin altered brain activity and effective connectivity in children with autism spectrum disorder during social perception tasks. Oxytocin increased connectivity within mesocorticolimbic reward circuitry and between mesolimbic seeds and social-perception regions, preferentially for social or rewarding stimuli.
Key findings
- Oxytocin increased right posterior superior temporal sulcus response to coherent biological motion versus scrambled motion; under placebo, this response was not strongly differentiated.
- Oxytocin increased right brainstem and right amygdala activation to angry versus happy voices; no clusters showed happy > angry for oxytocin > placebo.
- During biological motion, oxytocin increased psychophysiological interaction connectivity between right nucleus accumbens and right ventrolateral/ventromedial prefrontal cortex; no clusters emerged for the left nucleus accumbens seed.
- During affective voices, oxytocin increased happy > angry connectivity with left and right nucleus accumbens and left and right amygdala seeds across regions including precuneus, cuneus, supramarginal gyrus/Heschl’s gyrus, and fusiform gyrus; no significant findings emerged for angry > happy. Higher SRS scores were associated with greater happy > angry connectivity in several regions, while ADI-R associations were mixed.
Methods
- Twenty-one children with ASD (8–16.5 years, 18 boys) were enrolled in a randomized, double-blind, placebo-controlled crossover design; final analyzed samples were 14 children (11 boys) for Biological Motion and 16 children (13 boys) for Affective Voices after motion-related exclusions.
- Participants received age-adjusted intranasal oxytocin (24 IU for 16–19 years, 18 IU for 12–15 years, 12 IU for 7–11 years) or placebo before fMRI; scans included a Biological Motion task (coherent vs scrambled motion) and an Affective Voices task (happy vs angry voices).
- Analyses used whole-brain main effects and psychophysiological interaction (PPI) analyses with nucleus accumbens and amygdala seeds; group-level models included age, full-scale IQ, and sex as covariates, with exploratory SRS and ADI-R regressors.
Limitations
- The paper states that some participants were on preexisting medication regimens, that the sample was small with relatively few girls, and that future work should address dose effects and compare children with ASD to typically developing children.
- The text makes evident that there was no typically developing comparison group, the study assessed a single oxytocin challenge rather than lasting therapeutic benefit, and motion artifact excluded several datasets.
- The symptom-severity findings were exploratory, and the unexpected amygdala–primary visual connectivity finding was interpreted post hoc and requires further validation.
Model-written summary. Check it against the paper before relying on it.
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Cites
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Claims the paper makes
0 of 13 cited sources checked · 0 supported · 0 flagged
- Findingown data
Oxytocin administration is associated with greater psychophysiological interaction between right nucleus accumbens and a region of ventral prefrontal cortex, peaking in right ventrolateral prefrontal cortex and extending into right ventromedial prefrontal cortex, during coherent versus scrambled biological motion.
“OT administration was associated with a greater PPI between right NAcc and a region of ventral PFC. This cluster had a peak in right ventrolateral PFC (vlPFC) and extended into right ventromedial PFC (vmPFC).”
- Also stated in: § Discussion · plain
“In the visual domain, inhalation of OT (relative to PLC) increased connectivity within the mesocorticolimbic pathway during the perception of coherent biological motion, specifically between NAcc and frontal regions (i.e., vm/vlPFC) known to be involved in representing reward value, social meaning, and social intentions4748.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
Oxytocin administration induces connectivity increases with all seeds of interest (left and right nucleus accumbens and left and right amygdala) for happy versus angry voices.
“OT administration induced connectivity increases with all seeds of interest (left and right NAcc and left and right AMYG) for HAP > ANG (see Fig. 3A).”
Quote in the paperSubstantial claim - Findingown data
Oxytocin enhances connectivity between nodes of the brain's reward and socioemotional processing systems.
“Further, OT enhances connectivity between nodes of the brain’s reward and socioemotional processing systems, and does so preferentially for social (versus nonsocial) stimuli.”
- Also stated in: § Discussion · plain
“Across visual and auditory modalities, OT increased effective connectivity both within the mesocorticolimbic reward pathway and also between mesolimbic sites and cortical regions that contribute to social perception.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
Intranasal oxytocin administration in individuals with autism spectrum disorder increases activity in brain regions important for perceiving social-emotional information.
“we show that OT administration in ASD increases activity in brain regions important for perceiving social-emotional information.”
- Also stated in: § Discussion · plain
“OT administration to children and adolescents with ASD was associated with increased activity in brain regions important for social-emotional perception.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
Oxytocin-induced connectivity increases are specific to socially rewarding (happy) versus socially aversive (angry) stimuli.
“These effects were specific to exposure to social versus nonsocial information (Biological Motion), and to socially rewarding versus socially aversive stimuli (Affective Voices).”
Quote in the paperSubstantial claim
- Findingown data
Oxytocin-induced connectivity increases are specific to social versus nonsocial stimuli.
“and does so preferentially for social (versus nonsocial) stimuli.”
- Also stated in: § Discussion · plain
“These effects were specific to exposure to social versus nonsocial information (Biological Motion), and to socially rewarding versus socially aversive stimuli (Affective Voices).”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
Right brainstem and right amygdala show greater activation to angry than happy voices under oxytocin versus placebo.
“Regions of right brainstem and right AMYG demonstrated greater activation to ANG than HAP, specifically under OT versus PLC; under PLC, these sites demonstrated deactivation to ANG voices, compared to relatively less deactivation or minimal activation to HAP (Fig. 2B, Table 3).”
- Also stated in: § Discussion · plain
“In the auditory domain, OT enhanced activation to ANG versus HAP voices in right brainstem and in a region with a peak in right hippocampus but the majority of its extent contained within right AMYG.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
Right posterior superior temporal sulcus shows a more strongly positive response to coherent biological motion than to scrambled motion under oxytocin versus placebo.
“Right posterior superior temporal sulcus (pSTS) demonstrated a more strongly positive response to BIO than SCRAM under OT versus PLC; under PLC, brain response to BIO versus SCRAM stimuli was not strongly differentiated at this site (Fig. 2A, Table 3).”
- Also stated in: § Discussion · plain
“In the visual domain, consistent with previous research2937, OT enhanced response to human motion versus control stimuli in right posterior superior temporal sulcus (pSTS), a brain region that has been consistently characterized as playing a key role in biological motion perception in neurotypical individuals3839.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
A number of brain regions demonstrated a negative correlation between Autism Diagnostic Interview-Revised score and oxytocin-induced change in happy versus angry psychophysiological interaction value, such that greater oxytocin-induced increases in connectivity were associated with a history of less severe social symptomaticity.
“Conversely, a number of brain regions demonstrated a negative correlation between ADI-R score and OT-induced change in HAP > ANG PPI value, such that greater OT-induced increases in connectivity in these brain regions were associated with a history of less severe social symptomaticity.”
Quote in the paperSubstantial claim - Findingown data
Oxytocin-induced connectivity changes during happy versus angry voice perception are associated with the severity of social deficits.
“We identified a number of sites for which OT-induced connectivity changes during HAP > ANG were associated with the severity of social deficits.”
Quote in the paperSubstantial claim - Findingown data
During Biological Motion, no brain regions showed a significant association between symptom severity and oxytocin-induced change in coherent versus scrambled effective connectivity.
“During Biological Motion, we found no brain regions for which a significant association between symptom severity and OT-induced change in BIO > SCRAM effective connectivity existed.”
Quote in the paperNot a substantial claim - Findingown data
Oxytocin increases connectivity between nucleus accumbens and prefrontal regions, including ventromedial prefrontal cortex and orbitofrontal cortex, during biological motion perception.
“During biological motion perception, we found that OT increases connectivity between NAcc and prefrontal regions, including vmPFC and orbitofrontal cortex (OFC).”
Quote in the paperSubstantial claim - Findingown data
During Affective Voices, higher Social Responsiveness Scale score (greater impairment) is associated with greater happy versus angry psychophysiological interaction values between seeds of interest and a variety of brain regions.
“However, during Affective Voices, a higher SRS score (indicating greater impairment) was associated with greater HAP > ANG PPI values between seeds of interest and a variety of brain regions.”
Quote in the paperNot a substantial claim - Findingown data
Children with more severe current symptomaticity (Social Responsiveness Scale) show greater increases in connectivity between bilateral nucleus accumbens or right amygdala and temporo-occipital sites relevant to social perception, and frontal sites such as ventromedial prefrontal cortex relevant to social motivation.
“Children whose parents endorsed more severe current symptomaticity (via SRS) demonstrated greater increases in connectivity between bilateral NAcc or right AMYG and 1) temporo-occipital sites relevant to social perception, and 2) frontal sites (e.g., vmPFC) relevant to social motivation.”
Quote in the paperSubstantial claim - Findingown data
Oxytocin increases connectivity between nucleus accumbens and primary auditory cortex specifically to happy versus angry voices.
“While participants listened to emotional voices, intranasal OT increased the connectivity between NAcc and primary auditory cortex, specifically to happy versus angry voices.”
Quote in the paperSubstantial claim - Findingown data
Children with a more severe symptom history (Autism Diagnostic Interview-Revised) show greater increases in connectivity between right nucleus accumbens and frontal pole.
“Children with a more severe symptom history (as assessed via ADI-R) also showed greater increases in connectivity between right NAcc and frontal pole.”
Quote in the paperNot a substantial claim - Findingown data
A less severe symptom history is associated with greater increases in connectivity between left nucleus accumbens or left amygdala and ventromedial prefrontal cortex.
“A less severe symptom history was associated with greater increases in connectivity between left NAcc or left AMYG and vmPFC.”
Quote in the paperNot a substantial claim - Findingown data
Intranasal oxytocin enhanced effective connectivity between mesolimbic sites and cortical regions involved in value coding and social perception in children and adolescents with ASD.
“OT enhanced effective connectivity between mesolimbic sites and cortical regions involved in value coding and social perception in children and adolescents with ASD.”
Quote in the paperSubstantial claim - Interpretationreasoning
The findings suggest a mechanism by which intranasal oxytocin may bolster social motivation.
“Our findings suggest a mechanism by which intranasal OT may bolster social motivation—one that could, in future, be harnessed to augment behavioral treatments for ASD.”
Quote in the paperSubstantial claim - Interpretationown data
Upregulation of right brainstem and amygdala when perceiving angry voices suggests a particular need for caution in the clinical use of oxytocin.
“The upregulation of these regions (which are key to the encoding of emotionally salient stimuli44) when perceiving angry voices suggests a particular need for caution in the clinical use of OT.”
Quote in the paperSubstantial claim - Interpretationown data
Oxytocin effects on systems underpinning social motivation are best observed in the context of rewarding social stimuli.
“We note that the effects we observed were context-specific; OT effects on systems underpinning social motivation are best observed in the context of rewarding social stimuli.”
Quote in the paperSubstantial claim - Interpretationown data
Oxytocin may also upregulate encoding of negative social experiences when these occur.
“While our effective connectivity analyses (discussed below) suggest that youth with ASD, when exposed to positive social stimuli under OT, show upregulation of reward systems, these findings suggest that OT may also upregulate encoding of negative social experiences when these occur.”
Quote in the paperSubstantial claim - Interpretationown data
Oxytocin-induced upregulation of right posterior superior temporal sulcus response to human motion in youth with autism spectrum disorder suggests oxytocin may promote a more neurotypical profile of engagement during a common social perception task.
“The OT-induced upregulation of right pSTS response to human motion in our sample of youth with ASD suggests that OT administration may have the potential to promote a more neurotypical profile of engagement during a common social perception task.”
Quote in the paperSubstantial claim - Interpretationreasoning
Oxytocin-induced increases in amygdala-posterior precuneus interactions might be related to remembering previous experience with happy cues and their reward value.
“Together, these findings suggest that OT-induced increases in AMYG-posterior PCu interactions might be related to remembering previous experience with happy cues and their reward value.”
Quote in the paperNot a substantial claim - Interpretationreasoning
One reason for the mixed clinical effects of chronic oxytocin administration observed thus far may be lack of sufficient control over the experiences to which individuals with autism spectrum disorder are exposed during oxytocin's window of effect.
“One reason for the mixed clinical effects of chronic OT administration observed thus far1213 may be lack of sufficient control over the experiences to which individuals with ASD are exposed during OT’s window of effect.”
Quote in the paperSubstantial claim - Interpretationown data
Oxytocin may facilitate social motivation by upregulating communication among regions related to motivational valuation, social perception, thinking about the self, and reward memory.
“Our findings indicate that by upregulating communication among regions related to motivational valuation, social perception, thinking about the self, and reward memory, OT may facilitate social motivation.”
Quote in the paperSubstantial claim - Interpretationown data
The results support the hypothesis that oxytocin increases communication among neural systems relevant to social motivation in autism spectrum disorder.
“These results support our hypothesis that OT increases communication among neural systems relevant to social motivation in ASD.”
Quote in the paperSubstantial claim - Interpretationown data
Oxytocin administration has differential effects depending on the social cues present, in accordance with the Social Salience hypothesis.
“Our results demonstrate that, in accordance with the assertions of the Social Salience23 hypothesis, OT administration has differential effects depending on the social cues present.”
Quote in the paperSubstantial claim - Premisecitation
Oxytocin enhances the function of several key nodes of the social brain in ASD.
“While we have recently reported on OT’s ability to enhance the function of several key nodes of the social brain in ASD37”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [37] Gordon, I. et al. Oxytocin enhances brain function in children with autism. Proceedings of the National Academy of Sciences of the United States of America 110, 20953–20958, doi: 10.1073/pnas.1312857110 (2013). source
Not checked in the free run.
- Study design and conductcitation
The psychophysiological interaction model specification ensures results only indicate effects over and above those explained by co-activation related to the task main effect or anatomical connections that lead to pervasively correlated activity regardless of task condition.
“Importantly, the model specification for this analysis ensures that results will only indicate effects over and above those explained by either co-activation related to the task main effect or anatomical connections that lead to pervasively correlated activity regardless of task condition33.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [33] O’Reilly, J. X., Woolrich, M. W., Behrens, T. E. J., Smith, S. M. & Johansen-Berg, H. Tools of the trade: psychophysiological interactions and functional connectivity. Social cognitive and affective neuroscience 7, 604–609, doi: 10.1093/scan/nss055 (2012). source
Not checked in the free run.
- Premisecitation
Oxytocin enhances neural attunement to visual social cues.
“our own neuroimaging work demonstrating OT-enhanced neural attunement to visual social cues37”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [37] Gordon, I. et al. Oxytocin enhances brain function in children with autism. Proceedings of the National Academy of Sciences of the United States of America 110, 20953–20958, doi: 10.1073/pnas.1312857110 (2013). source
Not checked in the free run.
- Interpretationreasoning
Intranasal oxytocin, via its effects on the neural underpinnings of social motivation, could improve response to behavioral interventions that provide a rich array of social learning opportunities.
“These findings lead us to believe that intranasal OT, via its effects on the neural underpinnings of social motivation, could improve response to behavioral interventions that provide a rich array of social learning opportunities.”
Quote in the paperSubstantial claim- Rests on an assumption: Oxytocin-induced changes in the neural underpinnings of social motivation translate into improved response to behavioral interventions in children with ASD.
- Rests on an assumption: Changes in mesocorticolimbic connectivity cause changes in social motivation in individuals with ASD.
- Study design and conductown data
Adding a regressor for the difference in motion outlier percentage between oxytocin and placebo scans did not change the results of the PPI analysis for the vocal affect paradigm.
“The addition of this regressor did not change the results of the PPI analysis.”
Quote in the paperNot a substantial claim
- May combine two claims. 12
- Classified as probably not a substantial claim. 14
May combine two claims.
Findingown dataHigher Autism Diagnostic Interview-Revised social subscale score (greater impairment) is associated with greater happy versus angry psychophysiological interaction values between left amygdala and right frontal pole, and between either left or right nucleus accumbens and ventromedial prefrontal cortex.
“Consistent with the SRS findings, a higher ADI-R social subscale score (indicating greater impairment) was associated with greater HAP > ANG PPI values between left AMYG and right frontal pole as well as between either left or right NAcc and vmPFC.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataDuring happy voice perception, oxytocin induces increases in connectivity with precuneus from both mesolimbic sites, with nucleus accumbens interacting with more anterior precuneus and amygdala with more posterior precuneus.
“During happy voice perception, OT also induced increases in connectivity with PCu from both mesolimbic sites, with NAcc interacting with more anterior regions of PCu and AMYG interacting with more posterior PCu regions.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductcitationPassive paradigms were employed to assess oxytocin's effects on social perception in the absence of potentially confounding task demands.
“We employed passive paradigms in order to assess OT’s effects on social perception in the absence of potentially confounding task demands (e.g., refs 29, 30, 31, 32).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [29] Kaiser, M. D. et al. Neural signatures of autism. Proc Natl Acad Sci USA 107, 21223–21228, doi: 10.1073/pnas.1010412107 (2010). source
Not checked in the free run.
- cites [30] Belin, P., Fillion-Bilodeau, S. & Gosselin, F. The Montreal Affective Voices: a validated set of nonverbal affect bursts for research on auditory affective processing. Behavior research methods 40, 531–539 (2008). source
Not checked in the free run.
- cites [31] Kanwisher, N., McDermott, J. & Chun, M. M. The fusiform face area: A module in human extrastriate cortex specialized for face perception. J. Neurosci. 17, 4302–4311 (1997). source
Not checked in the free run.
May combine two claims.
InterpretationreasoningThe findings support the notion that, in the normal course of social interaction, oxytocin serves different functions in different contexts; when highly salient but not rewarding angry cues are present, it upregulates amygdala response, whereas when happy cues are present, oxytocin facilitates communication among sites important for social motivation.
“Thus our findings support the notion that, in the normal course of social interaction, OT serves different functions in different contexts22; when highly salient (but not rewarding) angry cues are present, it upregulates AMYG response, whereas when happy cues are present, OT facilitates communication among sites that are important for social motivation.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataOxytocin administration can lead to beneficial effects on neural function in a range of individuals with autism spectrum disorder, but understanding individual symptomaticity is necessary to predict variability in oxytocin's therapeutic potential.
“We propose that OT administration can lead to beneficial effects on neural function in a range of individuals with ASD, but that understanding individual symptomaticity is necessary to predict variability in OT’s therapeutic potential.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataQuality assurance review excluded datasets contaminated by excessive motion, yielding final Biological Motion and Affective Voices samples of 14 and 16 children, respectively.
“After quality assurance review to exclude datasets contaminated by excessive motion, our final Biological Motion sample included 14 children (11 boys), and our Affective Voices sample included 16 children (13 boys).”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductown dataThe study used a randomized, double-blind, placebo-controlled crossover design in which 21 children with autism spectrum disorder received oxytocin or placebo before an initial fMRI scan and the other agent before a second fMRI scan.
“To test this hypothesis, we employed a randomized, double-blind, placebo-controlled crossover design in which 21 children with ASD (8–16.5y, 18 boys; see Table 1 for demographic and phenotypic characteristics) received either OT or placebo (PLC) prior to an initial fMRI scan.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationOxytocin can increase processing efficiency at the neuronal level by optimizing signal-to-noise during cell firing.
“Together with recent findings showing that OT can increase processing efficiency at the neuronal level by optimizing signal-to-noise during cell firing43”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [43] Owen, S. F. et al. Oxytocin enhances hippocampal spike transmission by modulating fast-spiking interneurons. Nature 500, 458–462, doi: 10.1038/nature12330 (2013). source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataThe final Biological Motion sample included 14 children (11 boys), and the Affective Voices sample included 16 children (13 boys).
“Our final Biological Motion sample included 14 children (11 boys), and our Affective Voices sample included 16 children (13 boys).”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim. May combine two claims.
Study design and conductnone givenPlacebo and oxytocin spray containers were prepared to look identical and were counterbalanced to be randomly assigned by the pharmacy.
“PLC and OT spray containers were prepared to look identical and were counterbalanced to be randomly assigned by the pharmacy as well.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductnone givenResearchers and participants were blinded to the content of the spray.
“Researchers, as well as participants, were blinded to the content of the spray.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningBy impacting mesocorticolimbic connectivity, oxytocin may create a neural background in individuals with ASD that could bolster the motivation to interact socially and allow them to be more open to learn social engagement skills during treatment.
“By impacting mesocorticolimbic connectivity, OT may create a neural background in individuals with ASD that could bolster the motivation to interact socially and allow them to be more open to learn social engagement skills during treatment.”
Quote in the paperSubstantial claim- Rests on an assumption: Changes in mesocorticolimbic connectivity cause changes in social motivation in individuals with ASD.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataDue to motion artifact, complete datasets from 6 children were excluded from analyses of the Biological Motion task, and 4 complete datasets were excluded from the Affective Voices task.
“Due to motion artifact, the complete datasets from 6 children were excluded from analyses of the Biological Motion task, and 4 complete datasets were excluded from the Affective Voices task.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningIn ASD, oxytocin may not only enhance neural activity to preferred stimuli but also improve communication among brain regions involved in social motivation and perception.
“these results show that in ASD, OT may not only serve to enhance neural activity to “preferred” stimuli, but also improve communication among brain regions involved in social motivation and perception.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [43] Owen, S. F. et al. Oxytocin enhances hippocampal spike transmission by modulating fast-spiking interneurons. Nature 500, 458–462, doi: 10.1038/nature12330 (2013). source
Not checked in the free run.
- cites [37] Gordon, I. et al. Oxytocin enhances brain function in children with autism. Proceedings of the National Academy of Sciences of the United States of America 110, 20953–20958, doi: 10.1073/pnas.1312857110 (2013). source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenOne participant could not complete both visits and was excluded.
“One participant could not complete both visits and was excluded.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductcitationParticipants were excluded if they had movement in any dimension ≥4 mm and/or ≥25% of volumes identified as outliers according to DVARS, such that only participants with acceptable motion under both oxytocin and placebo visits were included.
“we elected to exclude participants where for either visit, the participant had one or more of the following: movement in any dimension ≥4 mm, and/or ≥25% of volumes identified as outliers according to the DVARS metric72 such that only participants who displayed acceptable amounts of motion under both the OT and PLC visits were included in analysis.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [72] Power, J. D., Barnes, K. A., Snyder, A. Z., Schlaggar, B. L. & Petersen, S. E. Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. NeuroImage 59, 2142–2154, doi: 10.1016/j.neuroimage.2011.10.018 (2012). source
Not checked in the free run.
Classified as probably not a substantial claim.
InterpretationreasoningThe current results illustrate a discrete aspect of oxytocin's effect captured by measures of connectivity.
“the current results illustrate a discrete aspect of OT’s effect captured by measures of connectivity”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [37] Gordon, I. et al. Oxytocin enhances brain function in children with autism. Proceedings of the National Academy of Sciences of the United States of America 110, 20953–20958, doi: 10.1073/pnas.1312857110 (2013). source
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductown dataThe study used a randomized, double-blind, placebo-controlled crossover design.
“We used a randomized, double blind, placebo-controlled crossover design.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataFor the vocal affect perception paradigm, fewer motion outlier volumes were detected for oxytocin than placebo scans (3.6 versus 5.5% of all time points identified as outliers), although there were no significant differences across treatment conditions as characterized by RMS movement metrics.
“For the vocal affect perception paradigm, fewer motion outlier volumes were detected for OT than PLC scans (3.6 versus 5.5% of all time points identified as outliers, respectively), although there were no significant differences across treatment conditions as characterized by RMS movement metrics.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataAge, full scale IQ, and sex were included as covariates in the group-level analysis.
“Age (de-meaned), full scale IQ (de-meaned), and sex (dummy coded, female = 1) were included as covariates.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductcitationASD diagnosis was confirmed using the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview - Revised (ADI-R).
“with ASD diagnosis confirmed using the Autism Diagnostic Observation Schedule70 and the Autism Diagnostic Interview – Revised (ADI-R)35.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [70] Lord, C. et al. The Autism Diagnostic Observation Schedule-Generic: A standard measure of social and communication deficits associated with the spectrum of autism. J. Autism Dev. Disord. 30, 205–223 (2000). source
Not checked in the free run.
- cites [35] Lord, C., Rutter, M. & Le Couteur, A. Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of autism and developmental disorders 24, 659–685 (1994). source
Not checked in the free run.
The paper relies on this without support.
There is a lack of sensitive, objective measures designed to illuminate mechanisms of change in oxytocin treatment for autism spectrum disorder.
“Our understanding of the potential for OT to treat ASD is hampered by a lack of sensitive, objective measures that are designed to illuminate mechanisms of change.”
The paper relies on this without support.
There have been few studies of oxytocin's effects on brain activity in children, creating a translational gap between the push for clinical use of oxytocin and limited understanding of developmental and contextual factors shaping its effects on neural function and behavior.
“Despite cautionary calls16 regarding the use of OT to treat ASD prior to understanding its developmental effects, there have been few studies of OT’s effects on brain activity in children, creating a translational gap between the push for clinical use of OT and our limited understanding of the developmental and contextual factors that shape its effects on neural function and resulting behavior.”
The paper relies on this without support.
Oxytocin-induced changes in the neural underpinnings of social motivation translate into improved response to behavioral interventions in children with ASD.
“These findings lead us to believe that intranasal OT, via its effects on the neural underpinnings of social motivation, could improve response to behavioral interventions that provide a rich array of social learning opportunities.”
The paper relies on this without support.
Changes in mesocorticolimbic connectivity cause changes in social motivation in individuals with ASD.
“By impacting mesocorticolimbic connectivity, OT may create a neural background in individuals with ASD that could bolster the motivation to interact socially and allow them to be more open to learn social engagement skills during treatment.”
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?
Acute IN-OT enhanced functional connectivity between PFC and NAc while viewing biological motion.
“In a separate study, acute IN-OT enhanced functional connectivity between PFC and NAc while viewing biological motion [49].”
From Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry (2021) · cites this paper as [49]
Intranasal OXT leads to increased activation in brain regions involved in perceiving and thinking about social-emotional information and enhances effective connectivity between nodes of the brain's reward and socioemotional processing systems.
“At the neural networks level, it has been shown that intranasal OXT leads to increased activation in the brain regions known to be involved in perceiving and thinking about social-emotional information and enhances effective connectivity between nodes of the brain’s reward and socioemotional processing systems [87, 88].”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [87]
Exogenous oxytocin has behavioural effects in humans, particularly in social deficit-related psychiatric disorders such as autism and schizophrenia.
“Exogenous oxytocin in humans also appears to have behavioural effects, particularly in such social deficit-related psychiatric disorders as autism and schizophrenia9–13.”
From Vascular RAGE transports oxytocin into the brain to elicit its maternal bonding behaviour in mice (2019) · cites this paper as [12]
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.
- Consistentr(14) = 0.28reported p = .3 · recomputed p = .294
“r(14) = 0.28, p = .300”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
ADI-R connectivity finding is attributed to the wrong seed-region pair
MajorThe Discussion says greater historical symptom severity was associated with increased connectivity between right NAcc and frontal pole. The Results instead assign the frontal-pole finding to left AMYG and the right-NAcc finding to vmPFC.
“Children with a more severe symptom history (as assessed via ADI-R) also showed greater increases in connectivity between right NAcc and frontal pole.”
“a higher ADI-R social subscale score (indicating greater impairment) was associated with greater HAP > ANG PPI values between left AMYG and right frontal pole as well as between either left or right NAcc and vmPFC.”
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- Authors
- Gordon, I., Jack, A., Pretzsch, C. M., Vander Wyk, B., Leckman, J. F., Feldman, R., & Pelphrey, K. A.
- Affiliations
- Bar-Ilan University (IL)
- George Washington University (US)
- Yale University (US)
- Corresponding author
- Gordon, Ilanit
- Jack, Allison
- ORCID
- Venue
- Scientific Reports
- Published
- 2016-11-15
- Volume
- 6
- Issue
- 1
- Pages
- 35054-35054
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5109935
- OpenAlex
- W2557098163
- Semantic Scholar
- 11df315f0b4eac8b46cf0b4ff14816fe4a637f5b
- Cited by
- 114
- References
- 77
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 5 · 2023: 13 · 2022: 17 · 2021: 18 · 2020: 11 · 2019: 14 · 2018: 9 · 2017: 12
- FWCI
- 18.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Science Foundation
- Yale University
- Lee Foundation
- National Institutes of Health (MH018268-31, UL1TR001863)
- National Institute of Mental Health (T32MH018268)
- National Center for Advancing Translational Sciences
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Social Sciences › Psychology › Social Psychology › Action Observation and Synchronization
- Keywords
- intranasal oxytocin, autism spectrum disorder, social motivation, social perception, mesolimbic reward pathway, nucleus accumbens, amygdala, brain connectivity, social-emotional processing, biological motion, voice emotion perception, children
- MeSH terms
- Autism Spectrum Disorder, Administration, Intranasal, Adolescent, Brain, Brain Mapping, Child, Double-Blind Method, Female, Humans, Magnetic Resonance Imaging, Male, Motivation, Oxytocin, Social Perception, Cross-Over Studies
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