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Randomized Controlled Trial
, 7 (4), e1099

Intranasal Oxytocin Enhances Intrinsic Corticostriatal Functional Connectivity in Women

Randomized Controlled Trial

Intranasal Oxytocin Enhances Intrinsic Corticostriatal Functional Connectivity in Women

R A I Bethlehem et al. Transl Psychiatry.


Oxytocin may influence various human behaviors and the connectivity across subcortical and cortical networks. Previous oxytocin studies are male biased and often constrained by task-based inferences. Here, we investigate the impact of oxytocin on resting-state connectivity between subcortical and cortical networks in women. We collected resting-state functional magnetic resonance imaging (fMRI) data on 26 typically developing women 40 min following intranasal oxytocin administration using a double-blind placebo-controlled crossover design. Independent components analysis (ICA) was applied to examine connectivity between networks. An independent analysis of oxytocin receptor (OXTR) gene expression in human subcortical and cortical areas was carried out to determine plausibility of direct oxytocin effects on OXTR. In women, OXTR was highly expressed in striatal and other subcortical regions, but showed modest expression in cortical areas. Oxytocin increased connectivity between corticostriatal circuitry typically involved in reward, emotion, social communication, language and pain processing. This effect was 1.39 standard deviations above the null effect of no difference between oxytocin and placebo. This oxytocin-related effect on corticostriatal connectivity covaried with autistic traits, such that oxytocin-related increase in connectivity was stronger in individuals with higher autistic traits. In sum, oxytocin strengthened corticostriatal connectivity in women, particularly with cortical networks that are involved in social-communicative, motivational and affective processes. This effect may be important for future work on neurological and psychiatric conditions (for example, autism), particularly through highlighting how oxytocin may operate differently for subsets of individuals.

Conflict of interest statement

The authors declare no conflict of interest.


Figure 1
Figure 1
Oxytocin receptor (OXTR) gene expression in the female human brain. This figure illustrates OXTR gene expression measured via RNAseq in BrainSpan ( and GTEx ( data sets. (a) Expression for all subcortical regions available in the GTEx data set in women. All brain regions show significant expression of OXTR above 0 and compared to expression in non-brain (skin) tissue. On-average, OXTR expression is particularly enriched in ventral striatum (nucleus accumbens), substantia nigra and hypothalamus. (b) Expression for all cortical areas and the thalamus available in the BrainSpan atlas in women. All areas also show significant, albeit modest, levels of OXTR expression compared to 0 and non-brain (skin) tissue.
Figure 2
Figure 2
Oxytocin-related enhancement of intrinsic functional connectivity. (a) The spatial map of component IC11. Voxels are colored by Z-statistics indicating how well each voxel's time series fits the component's time series. (b) The same information for component IC21. (c) The top 100 terms associated with component IC11 based on NeuroSynth decoding and font size represents relative correlation strength of that term to the component. (d) The same information for component IC21. (e) Connectivity between IC11 and IC21 for each subject during placebo or oxytocin administration. Dots represent individual subjects and the lines connect each individual's data under placebo and oxytocin, with the positive slopes indicating an enhancement of connectivity after oxytocin administration. Underneath the individual-level data are boxplots that indicate the median, interquartile range and outer fences. Interestingly, the two individuals who would be considered outliers in the placebo condition are the minority of individuals showing no enhancement of connectivity as a function of oxytocin. (f) The relationship between oxytocin-related effects on connectivity and continuous variation in autistic traits as measured by the AQ. (g) The between-component connectivity of between comparable components of the normative data set. (h) The spatial correlation between the oxytocin data components and the two normative components that were selected. (i, j) The normative components spatial maps.

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