Live agent preference and social action monitoring in the macaque mid-superior temporal sulcus region

Mentalizing, the ability to infer the mental states of others, is a cornerstone of adaptive social intelligence. While functional brain mapping of human mentalizing has progressed considerably, its evolutionary signature in nonhuman primates remains debated. The discovery that the middle part of the macaque superior temporal sulcus (mid-STS) region has a connectional fingerprint most similar to the human temporoparietal junction (TPJ)—a crucial node in the mentalizing network—raises the possibility that these cortical areas may also share basic functional properties associated with mentalizing. Here, we show that this is the case in aspects of a preference for live social interactions and in a theoretical framework of predictive coding. Macaque monkeys were trained to perform a turn-taking choice task with another real monkey partner sitting directly face-to-face or a filmed partner appearing in prerecorded videos. We found that about three-fourths of task-related mid-STS neurons exhibited agent-dependent activity, most responding selectively or preferentially to the partner’s action. At the population level, activities of these partner-type neurons were significantly greater under live-partner compared to video-recorded–partner task conditions. Furthermore, a subset of the partner-type neurons responded proactively when predictions about the partner’s action were violated. This prediction error coding was specific to the action domain; almost none of the neurons signaled error in the prediction of reward. The present findings highlight unique roles of the macaque mid-STS at the single-neuron level and further delineate its functional parallels with the human TPJ in social cognitive processes associated with mentalizing.

Recruitment and retention of participant and study partner dyads in two multinational Alzheimer’s disease registration trials

Background Early study exit is detrimental to statistical power and increases the risk for bias in Alzheimer’s disease clinical trials. Previous analyses in early phase academic trials demonstrated associations between rates of trial incompletion and participants’ study partner type, with participants enrolling with non-spouse study partners being at greater risk. Methods We conducted secondary analyses of two multinational phase III trials of semagacestat, an oral gamma secretase inhibitor, for mild-to-moderate AD dementia. Cox’s proportional hazards regression model was used to estimate the relationship between study partner type and the risk of early exit from the trial after adjustment for a priori identified potential confounding factors. Additionally, we used a random forest model to identify top predictors of dropout. Results Among participants with spousal, adult child, and other study partners, respectively, 35%, 38%, and 36% dropped out or died prior to protocol-defined study completion, respectively. In unadjusted models, the risk of trial incompletion differed by study partner type (unadjusted p value = 0.027 for test of differences by partner type), but in models adjusting for potential confounding factors, the differences were not statistically significant (p value = 0.928). In exploratory modeling, participant age was identified as the primary characteristic to explain the relationship between study partner type and the risk of failing to complete the trial. Participant age was also the strongest predictor of trial incompletion in the random forest model. Conclusions After adjustment for age, no differences in the risk of incompletion were observed when comparing participants with different study partner types in these trials. Differences between our findings and the findings of previous studies may be explained by differences in trial phase, size, geographic regions, or the composition of academic and non-academic sites.

Recruitment and Retention of Participant and Study Partner Dyads in Two Multinational Alzheimer’s Disease Registration Trials

Background: Early study exit is detrimental to statistical power and increases the risk for bias in Alzheimer’s disease clinical trials. Previous analyses in early phase academic trials demonstrated associations between rates of trial incompletion and participants’ study partner type, with participants enrolling with non-spouse study partners being at greater risk.Methods: We conducted secondary analyses of two multinational phase III trials of semagacestat, an oral gamma secretase inhibitor, for mild-to-moderate AD dementia. Cox’s proportional hazards regression model was used to estimate the relationship between study partner type and the risk of early exit from the trial after adjustment for a priori identified potential confounding factors. Additionally, we used a random forest model to identify top predictors of dropout.Results: Among participants with spousal, adult child, and other study partners, respectively, 35%, 38%, and 36% dropped out or died prior to protocol-defined study completion, respectively. In unadjusted models, the risk of trial incompletion differed by study partner type (unadjusted p-value=0.027 for test of differences by partner type), but in models adjusting for potential confounding factors the differences were not statistically significant (p-value=0.928). In exploratory modeling, participant age was identified as the primary characteristic to explain the relationship between study partner type and the risk of failing to complete the trial. Participant age was also the strongest predictor of trial incompletion in the random forest model.Conclusions: After adjustment for age, no qualitative differences in the risk of incompletion were observed when comparing participants with different study partner types in these trials. Differences between our findings and the findings of previous studies may be explained by differences in trial phase, size, geographic regions, or the composition of academic and non-academic sites.

Oxytocin and vasopressin modulation of prisoner’s dilemma strategies

Background: The neuropeptides oxytocin and vasopressin have been repeatedly implicated in social decision making by enhancing social salience and, generally, cooperation. The iterated and sequential version of the prisoner’s dilemma (PD) game is a social dilemma paradigm eliciting strategies of cooperation versus competition. Aims: We aimed to characterise the role of PD players’ sex, game partner type (computer vs. human) and oxytocin or vasopressin inhalation on the player’s strategy preference. Methods: Participants (153 men; 151 women) were randomised to intranasal 24 IU oxytocin, 20 IU vasopressin or placebo, double-blind, and played the PD. We examined main and interactive effects of sex, drug and partner type on strategy preference. Results: We found a pervasive preference for a tit-for-tat strategy (i.e. general sensitivity to the partner’s choices) over unconditional cooperation, particularly when against a human rather than a computer partner. Oxytocin doubled this sensitivity in women (i.e. the preference for tit-for-tat over unconditional cooperation strategies) when playing against computers, which suggests a tendency to anthropomorphise them, and doubled women’s unconditional cooperation preference when playing against humans. Vasopressin doubled sensitivity to the partner’s previous choices (i.e. for tit-for-tat over unconditional cooperation) across sexes and partner types. Conclusions: These findings suggest that women may be more sensitive to oxytocin’s social effects of anthropomorphism of non-humans and of unconditional cooperation with humans, which may be consistent with evolutionary pressures for maternal care, and that vasopressin, irrespective of sex and partner type, may be generally sensitising humans to others’ behaviour.

Study partner types and prediction of cognitive performance: implications to preclinical Alzheimer’s trials

Background Alzheimer’s disease (AD) clinical trials require enrollment of a participant and a study partner, whose role includes assessing participant cognitive and functional performance. AD trials now investigate early stages of the disease, when participants are not cognitively impaired. This gives rise to the question of whether study partners or participants provide more information in these trials. Methods We used data from the AD Cooperative Study Prevention Instrument Project (ADCS-PI) to compare participant and study partner predictions of the participant’s current and future cognitive state. We used the Cognitive Function Instrument (CFI) as a measure of evaluation of the participant’s cognitive status and the modified ADCS Preclinical Alzheimer’s Cognitive Composite (mADCS-PACC) as an objective measure of cognition. Stratifying by cognitive status and study partner type and adjusting for other predictors of the participant’s cognitive state, we used random forests along with estimated mean variable importance (eMVI) to assess how well each member of the dyad can predict cognitive state at current and later visits. We also fit linear regression models at each time point and for each scenario. Results Participants were better at predicting future cognitive status compared to their study partners regardless of study partner type, though the difference between participants and partners was greatest for non-spousal dyads in the lowest-performing quartile. Cross-sectional assessments differed substantially by dyad type. Within the lowest cognitive performance quartile, participants having a non-spousal study partner outperformed their partners in assessing cognition at later times. Spousal partners, in contrast, outperformed participants later in the study in predicting current cognitive performance. Conclusions These results indicate that participants tend to be better at predicting future cognition compared to their study partners regardless of the study partner type. When assessing current cognition, however, spousal study partners perform better at later time points and non-spousal study partners do not provide as much information regarding participant cognitive state.

Contextualizing condoms: a cross-sectional study mapping intersections of locations of sexual contact, partner type, and substance use as contexts for sexual risk behavior among MSM in Peru

Background Condomless anal intercourse (CAI) appears to be increasing among men who have sex with men (MSM) globally, and is reported to be as high as 70% in recent studies in Peru. To improve understanding of the evolving context of CAI among MSM in Peru, we studied associations between partner type, substance use, and condomless anal intercourse (CAI) in locations where MSM commonly report having sexual encounters. Methods In a 2017 cross-sectional study of rectal STI screening and HIV prevention, a convenience sample of MSM recruited from community venues in Lima completed a survey of demographic characteristics and sexual risk behavior with their three most recent partners. Generalized estimating equations estimated correlations of CAI with location of last sexual contact, participant substance use prior to sex, and negotiation of condom use before or during sex. The network data integration application, Cytoscape, mapped intersections of partner type, sexual orientation, substance use, and CAI by four types of locations where sex occurred: 1) Home, 2) Hotel, 3) Sauna or Internet Cabin, and 4) Public Spaces. Results Of 447 MSM (median age 27 years), 76.9% reported CAI with ≥1 of their last three partners. Participants reported sex with casual partners most commonly in homes (64.6%) and hotels (60.4%), and with anonymous partners most often in saunas/Internet cabins (57.5%) and public spaces (52.6%). CAI was less commonly reported in hotels (aPR, 95% CI: 0.85, 0.75–0.97) compared to homes. Participants who used marijuana before sex at home were more likely to report CAI than MSM who did not use marijuana (1.36, 1.01–1.92). Partner alcohol use before sex was associated with CAI in saunas/Internet cabins (3.17, 1.45–6.91) and public spaces (2.65, 1.41–4.98). In the sexual network maps, almost all MSM who used drugs prior to their sexual encounters used drugs with more than one of their last three partners. Conclusions CAI was common and associated with different risk factors, like partner type and substance use, based on location where sex occurred. Novel combination HIV, STI, and substance use prevention interventions must consider how the social environments of MSM influence condom use and other sexual risk behaviors. Trial registration ClinicalTrials.gov Identifier NCT03010020, January 4, 2017.