Null results of oxytocin and vasopressin administration on mentalizing in a large fMRI sample: evidence from a randomized controlled trial.

BACKGROUND: Although potential links between oxytocin (OT), vasopressin (AVP), and social cognition are well-grounded theoretically, most studies have included all male samples, and few have demonstrated consistent effects of either neuropeptide on mentalizing (i.e. understanding the mental states of others). To understand the potential of either neuropeptide as a pharmacological treatment for individuals with impairments in social cognition, it is important to demonstrate the beneficial effects of OT and AVP on mentalizing in healthy individuals. METHODS: In the present randomized, double-blind, placebo-controlled study (n = 186) of healthy individuals, we examined the effects of OT and AVP administration on behavioral responses and neural activity in response to a mentalizing task. RESULTS: Relative to placebo, neither drug showed an effect on task reaction time or accuracy, nor on whole-brain neural activation or functional connectivity observed within brain networks associated with mentalizing. Exploratory analyses included several variables previously shown to moderate OT's effects on social processes (e.g., self-reported empathy, alexithymia) but resulted in no significant interaction effects. CONCLUSIONS: Results add to a growing literature demonstrating that intranasal administration of OT and AVP may have a more limited effect on social cognition, at both the behavioral and neural level, than initially assumed. Randomized controlled trial registrations: ClinicalTrials.gov; NCT02393443; NCT02393456; NCT02394054.

Electrocorticographic evidence of a common neurocognitive sequence for mentalizing about the self and others.

Neuroimaging studies of mentalizing (i.e., theory of mind) consistently implicate the default mode network (DMN). Nevertheless, the social cognitive functions of individual DMN regions remain unclear, perhaps due to limited spatiotemporal resolution in neuroimaging. Here we use electrocorticography (ECoG) to directly record neuronal population activity while 16 human participants judge the psychological traits of themselves and others. Self- and other-mentalizing recruit near-identical cortical sites in a common spatiotemporal sequence. Activations begin in the visual cortex, followed by temporoparietal DMN regions, then finally in medial prefrontal regions. Moreover, regions with later activations exhibit stronger functional specificity for mentalizing, stronger associations with behavioral responses, and stronger self/other differentiation. Specifically, other-mentalizing evokes slower and longer activations than self-mentalizing across successive DMN regions, implying lengthier processing at higher levels of representation. Our results suggest a common neurocognitive pathway for self- and other-mentalizing that follows a complex spatiotemporal gradient of functional specialization across DMN and beyond.

Posttraumatic stress disorder and the social brain: Affect-related disruption of the default and mirror networks.

BACKGROUND: Social cognitive impairments, specifically in mentalizing and emotion recognition, are common and debilitating symptoms of posttraumatic stress disorder (PTSD). Despite this, little is known about the neurobiology of these impairments, as there are currently no published neuroimaging investigations of social inference in PTSD. METHODS: Trauma-exposed veterans with and without PTSD (n = 20 each) performed the Why/How social inference task during functional magnetic resonance imaging (fMRI). Patients with PTSD had two fMRI sessions, between which they underwent affect labeling training. We probed the primary networks of the "social brain"-the default mode network (DMN) and mirror neuron system (MNS)-by examining neural activity evoked by mentalizing and action identification prompts, which were paired with emotional and nonemotional targets. RESULTS: Hyperactivation to emotional stimuli differentiated PTSD patients from controls, correlated with symptom severity, and predicted training outcomes. Critically, these effects were nonsignificant or marginal for nonemotional stimuli. Results were generally consistent throughout DMN and MNS. Unexpectedly, effects were nonsignificant in core affect regions, but robust in regions that overlap with the dorsal attention, ventral attention, and frontoparietal control networks. CONCLUSIONS: The array of social cognitive processes subserved by DMN and MNS appear to be inordinately selective for emotional stimuli in PTSD. However, core affective processes do not appear to be the primary instigators of such selectivity. Instead, we propose that affective attentional biases may instigate widespread affect-selectivity throughout the social brain. Affect labeling training may inhibit such biases. These accounts align with numerous reports of affect-biased attentional processes in PTSD.

Sex Differences in the Relationship Between Inflammation and Reward Sensitivity: A Randomized Controlled Trial of Endotoxin.

BACKGROUND: There are robust sex differences in the prevalence of depression. Inflammation and anhedonia may play a role in understanding these sex differences. Indeed, sex differences in inflammation-induced neural responses to reward may provide insight into the sex gaps in depression, but no study has examined this question. METHODS: As such, the current study examined whether there were sex differences in reward-related neural activity (i.e., ventral striatum [VS] activity) in response to an experimental inflammatory challenge. Human participants (N = 115; 69 female) were randomly assigned to receive either placebo or low-dose endotoxin, which increases inflammation in a safe, time-limited manner. Two hours after receiving placebo or endotoxin (the height of the inflammatory response to endotoxin), participants completed a task in which they anticipated monetary reward in a functional magnetic resonance imaging scanner. RESULTS: Results demonstrated that endotoxin (vs. placebo) led to reduced VS activity in anticipation of reward and that there were sex differences in this effect. Specifically, in female participants, endotoxin (vs. placebo) led to decreased VS activity in anticipation of reward, but this effect was not present in male participants. In addition, within the endotoxin condition, decreases in VS activity in anticipation of reward were related to increases in inflammation for female but not male participants. CONCLUSIONS: These findings may have implications for understanding how inflammation may contribute to sex differences in rates of depression.

Social, self, (situational), and affective processes in medial prefrontal cortex (MPFC): Causal, multivariate, and reverse inference evidence.

The medial prefrontal cortex (MPFC) has been posited to serve a variety of social, affective, and cognitive functions. These conclusions have largely been driven by forward inference analyses (e.g. GLM fMRI studies and meta-analyses) that indicate where domain-specific tasks tend to produce activity but tell us little about what those regions do. Here, we take a multi-method, multi-domain approach to the functionality of MPFC subdivisions within Brodmann areas 9-11. We consider four methods that each have reverse inference or causal inference value: lesion work, transcranial magnetic stimulation, multivariate pattern analysis, and Neurosynth analyses. The Neurosynth analyses include multi-term reverse inference analyses that compare several domains of interest to one another at once. We examine the evidence supporting structure-function links in five domains: social cognition, self, value, emotional experience, and mental time travel. The evidence is considered for each of three MPFC subdivisions: dorsomedial prefrontal cortex (DMPFC), anteromedial prefrontal cortex (AMPFC), and ventromedial prefrontal cortex (VMPFC). Although there is evidentiary variability across methods, the results suggest that social processes are functionally linked to DMPFC (and somewhat surprisingly in VMPFC), self processes are linked to AMPFC, and affective processes are linked to AMPFC and VMPFC. There is also a relatively non-selective region of VMPFC that may support situational processing, a process key to each domain, but also independent of each.