Chronic oxytocin attenuates amygdala activity but does not improve mirror system function in autism
Poster No:
334
Submission Type:
Abstract Submission
Authors:
Kaat Alaerts1, Ruth Op de Beeck1, Nicky Daniels1, Matthijs Moerkerke1, Bart Boets1, Jellina Prinsen1
Institutions:
1KU Leuven, University of Leuven, Leuven, Vlaams-Brabant
First Author:
Co-Author(s):
Introduction:
Alterations in the action perception network or mirror system are proposed to underly social difficulties characteristic of autism spectrum disorder. Evidence to date is mixed however, with some studies demonstrating altered recruitment of the mirror system during action perception or imitation, while others demonstrated no deficit 1.
Intranasal administration of oxytocin is increasingly considered as a potential new therapeutic approach for mitigating social perception difficulties in autism, primarily through its social salience enhancing effects, facilitating attention to, and perception of social signals (e.g. from faces or bodily actions) 2.
Despite initial behavioral studies, little is known about oxytocin's role in modulating the neural correlates of mirror system functioning. Gaining a deeper understanding into the neuroplastic changes that underlie behavioral effects seems crucial, particularly upon receiving multiple-dose, chronic oxytocin administrations, as it allows delineating mechanisms of inter-individual variation in clinical treatment responses.
Intranasal administration of oxytocin is increasingly considered as a potential new therapeutic approach for mitigating social perception difficulties in autism, primarily through its social salience enhancing effects, facilitating attention to, and perception of social signals (e.g. from faces or bodily actions) 2.
Despite initial behavioral studies, little is known about oxytocin's role in modulating the neural correlates of mirror system functioning. Gaining a deeper understanding into the neuroplastic changes that underlie behavioral effects seems crucial, particularly upon receiving multiple-dose, chronic oxytocin administrations, as it allows delineating mechanisms of inter-individual variation in clinical treatment responses.
Methods:
The aim of the current study was two-fold: (i) to investigate mirror system functioning at the neural level in children with autism (aged 8-12 years; n=56, 13 girls) compared to children without autism (n=38, 7 girls); and (ii) to explore whether chronic oxytocin administration, compared to placebo could mitigate altered mirror system function in the cohort of children with autism (n=19 oxytocin, n=25 placebo).
To do so, a randomized, placebo-controlled pharmaco-neuroimaging trial was conducted, investigating the effects of chronic oxytocin administration (4 weeks, daily 24 IU) on brain activity related to action and gaze cue processing (Fig. 1). Stimuli encompassed a female model performing a simple hand movement (or static hand), while establishing direct (or averted) gaze. Mirror system function was assessed before and after the four-week oxytocin (or placebo) administration, within distinct regions-of-interests pertaining to the core fronto-parietal mirror system (inferior frontal gyrus (IFG), inferior parietal lobule (IPL), ventral premotor cortex (vPMC)) and the extended social brain network (medial prefrontal cortex (mPFC), superior temporal sulcus (STS), and amygdala).
To do so, a randomized, placebo-controlled pharmaco-neuroimaging trial was conducted, investigating the effects of chronic oxytocin administration (4 weeks, daily 24 IU) on brain activity related to action and gaze cue processing (Fig. 1). Stimuli encompassed a female model performing a simple hand movement (or static hand), while establishing direct (or averted) gaze. Mirror system function was assessed before and after the four-week oxytocin (or placebo) administration, within distinct regions-of-interests pertaining to the core fronto-parietal mirror system (inferior frontal gyrus (IFG), inferior parietal lobule (IPL), ventral premotor cortex (vPMC)) and the extended social brain network (medial prefrontal cortex (mPFC), superior temporal sulcus (STS), and amygdala).
Results:
Compared to the control group, children with autism displayed a significantly reduced recruitment of the core mirror system (IFG, IPL, vPMC), particularly upon hand movement observation (pIFG= .05; pIPL= .04; pvPMC= .005) (Fig. 2A). Regions of the social brain network (amygdala and STS) displayed overall stronger activity upon processing the hand movement, compared to observing the static hand, but no significant diagnosis-related differences were apparent in recruitment of this network (all p > .05). Also no significant modulations depending on eye gaze were revealed, either in the mirror system or social brain network.
Upon nasal spray administration, no significant modulation was revealed within any of the mirror system regions, indicating no mitigation of reduced mirror system function in autism by oxytocin. In line with prior studies 3, chronic oxytocin administration did induce an overall dampening in amygdala reactivity (pamygdala = .01; ηp2 = .12) (Fig. 2B). Furthermore, this attenuation was significantly associated with improved repetitive behaviors (Repetitive Behavior Scale) (Spearman ρ=.31, p=.046) and social functioning (Social Responsiveness Scale) (ρ=.29, p=.058), as well as with higher endogenous salivary oxytocin levels (ρ=-.34, p=.026) (Fig. 2C).
Upon nasal spray administration, no significant modulation was revealed within any of the mirror system regions, indicating no mitigation of reduced mirror system function in autism by oxytocin. In line with prior studies 3, chronic oxytocin administration did induce an overall dampening in amygdala reactivity (pamygdala = .01; ηp2 = .12) (Fig. 2B). Furthermore, this attenuation was significantly associated with improved repetitive behaviors (Repetitive Behavior Scale) (Spearman ρ=.31, p=.046) and social functioning (Social Responsiveness Scale) (ρ=.29, p=.058), as well as with higher endogenous salivary oxytocin levels (ρ=-.34, p=.026) (Fig. 2C).
Conclusions:
Chronic oxytocin administration did not mitigate reduced recruitment of the fronto-parietal mirror system during action perception, indicating no overall social salience enhancing effect of oxytocin. Instead, chronic oxytocin induced an overall dampening of amygdala recruitment, likely reflecting oxytocin's anxiolytic role in facilitating stress regulation 4.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Modeling and Analysis Methods:
Activation (eg. BOLD task-fMRI) 2
Keywords:
Autism
fMRI CONTRAST MECHANISMS
Pharmacotherapy
Psychiatric
Other - Oxytocin
1|2Indicates the priority used for review
·Figure 1
·Figure 2
Provide references using author date format
2 Shamay-Tsoory, S. G. & Abu-Akel, A. The Social Salience Hypothesis of Oxytocin. Biol. Psychiatry 79, 194-202 (2016). https://doi.org:S0006-3223(15)00639-3 [pii];10.1016/j.biopsych.2015.07.020 [doi]
3 Bernaerts, S., Boets, B., Steyaert, J., Wenderoth, N. & Alaerts, K. Oxytocin treatment attenuates amygdala activity in autism: a treatment-mechanism study with long-term follow-up. Transl Psychiatry 10, 383 (2020). https://doi.org:10.1038/s41398-020-01069-w
4 Stoop, R., Hegoburu, C. & van den Burg, E. New opportunities in vasopressin and oxytocin research: a perspective from the amygdala. Annu Rev Neurosci 38, 369-388 (2015). https://doi.org:10.1146/annurev-neuro-071714-033904