Discussion
neurodevelopmental disorders
LUDWIG
In this large fMRI study, we found no effects of OT or AVP Meta-analyses have found evidence of beneficial effects of OT on theory of mind in studies of people with neurodevelopmental disorders (Bürkner, Williams, Simmons, & Woolley, The lack of results for OT or AVP suggests that these neuropeptides may not influence mentalizing in healthy individuals. This is consistent with the results from Geng et al. (It must be noted that there is still skepticism about the use of intranasal OT and AVP administration due to methodological issues, and in particular, the unclear pharmacokinetics (Leng & Ludwig, The present results may also differ from previous studies using the RMET because it is possible that OT may more strongly affect emotion recognition than mentalizing processes. Although mentalizing and emotion recognition networks show overlap in the mPFC (Lieberman, Straccia, Meyer, Du, & Tan, Another possibility for the present findings is that the main effects of the Why/How task are too strong to see drug effects. Indeed, one of the primary strengths of the Why/How task compared to other mentalizing paradigms, such as the RMET, is the tight control it offers in parsing neural effects related to mental state inference The present study has a number of strengths including the use of one of the most well-validated fMRI tasks for reliably dissociating the mentalizing and mirror networks, indicating the rare ability amongst fMRI tasks of distinguishing mental state representations from perceptual and motor representations. We also demonstrate null results of both main effects and interaction effects related to measures previously observed to moderate the effects of OT or AVP on social cognitive processes.Since the majority of human studies examining the effects of OT and AVP has relied on all male samples, our majority female sample can be viewed as a strength and represents an important contribution to the literature (Quintana et al., In addition, our results only relate to the effects of OT or AVP approximately 90 min post-administration. The current consensus for the optimal amount of time for incubation is approximately 35–50 min before beginning the task. Therefore, our results may not represent the peak increase in OT concentrations (Quintana et al., Another limitation is that our between-subjects design limited overall power (Quintana et al., Last, it is important to note that in our preregistration in 2015, the Why/How task was overlooked and not listed because it was initially intended as a localizer for use in a separate task in the same broader study (a task described as ‘learning for teaching’). In addition, unfortunately, for logistical purposes, the larger study was separated into three different preregistrations based on different funding mechanisms (NCT02393443; NCT02393456; NCT02394054). Information on the overall study design and the other tasks, including an empathy task, a deception detection task, and a task involving viewing images of participants' attachment figures, were listed in the original preregistrations. Null results that are not preregistered, such as those in the present study, may be subject to biases such as reverse In sum, in a majority female non-clinical sample, we found no effects of either OT or AVP administration compared to placebo on behavioral responses, neural activation, or functional connectivity related to mentalizing, a social cognitive process that is impaired in several clinical populations. Furthermore, of the relevant moderators we explored, no associations survived after correction for multiple comparisons. These results, based on the well-validated Why/How task, support previous research showing a lack of an association between OT and several social processes (Tabak et al., 