Arndis Simonsen

Modulation of social influence by methylphenidate

The ability to infer value from the reactions of other people is a common and essential ability with a poorly understood neurobiology. Commonly, social learning matches ones values and behavior to what is perceived as normal for ones social group. This is known as conformity. Conformity of value correlates with neural activity shared by cognitions that depend on optimum catecholamine levels, but catecholamine involvement in conformity has not been tested empirically. Methylphenidate (MPH) is an indirect dopamine and noradrenalin agonist, commonly used for the treatment of attention-deficit hyperactivity disorder for which it reduces undesirable behavior as evaluated by peers and authority figures, indicative of increased conformity. We hypothesized that MPH might increase conformity of value. In all, 38 healthy adult females received either a single oral 20 mg dose of MPH or placebo (PL). Each subject rated 153 faces for trustworthiness followed immediately by the faces mean rating from a group of peers. After 30 min and a 2-back continuous-performance working-memory task, subjects were unexpectedly asked to rate all the faces again. Both the groups tended to change their ratings towards the social norm. The MPH group exhibited twice the conformity effect of the PL group following moderate social conflict, but this did not occur following large conflicts. This suggests that MPH might enhance signals that would otherwise be too weak to evoke conformity. MPH did not affect 2-back performance. We provide a new working hypothesis of a neurocognitive mechanism by which MPH reduces socially disruptive behavior and provides novel evidence of catecholamine mediation of social learning.

In for a Penny, in for a Pound: Methylphenidate Reduces the Inhibitory Effect of High Stakes on Persistent Risky Choice

Methylphenidate (MPH) is a stimulant that increases extracellular levels of dopamine and noradrenaline. It can diminish risky decision-making tendencies in certain clinical populations. MPH is also used, without license, by healthy adults, but the impact on their decision-making is not well established. Previous work has found that dopamine receptor activity of healthy adults can modulate the influence of stake magnitude on decisions to persistently gamble after incurring a loss. In this study, we tested for modulation of this effect by MPH in 40 healthy human adults. In a double-blind experiment, 20 subjects received 20 mg of MPH, while 20 matched controls received a placebo. All were provided with 30 rounds of opportunities to accept an incurred loss from their assets or opt for a “double-or-nothing” gamble that would either avoid or double it. Rounds began with a variable loss that would double with every failed gamble until it was accepted, recovered, or reached a specified maximum. Probability of recovery on any gamble was low and ambiguous. Subjects receiving placebo gambled less as the magnitude of the stake was raised and as the magnitude of accumulated loss escalated over the course of the task. In contrast, subjects treated with MPH gambled at a consistent rate, well above chance, across all stakes and trials. Trait reward responsiveness also reduced the impact of high stakes. The findings suggest that elevated catecholamine activity by MPH can disrupt inhibitory influences on persistent risky choice in healthy adults.

Enhanced automatic action imitation and intact imitation- inhibition in schizophrenia

Imitation plays a key role in social learning and in facilitating social interactions and likely constitutes a basic building block of social cognition that supports higher-level social abilities. Recent findings suggest that patients with schizophrenia have imitation impairments that could contribute to the social impairments associated with the disorder. However, extant studies have specifically assessed voluntary imitation or automatic imitation of emotional stimuli without controlling for potential confounders. The imitation impairments seen might therefore be secondary to other cognitive, motoric, or emotional deficits associated with the disorder. To overcome this issue, we used an automatic imitation paradigm with nonemotional stimuli to assess automatic imitation and the top-down modulation of imitation where participants were required to lift one of 2 fingers according to a number shown on the screen while observing the same or the other finger movement. In addition, we used a control task with a visual cue in place of a moving finger, to isolate the effect of observing finger movement from other visual cueing effects. Data from 33 patients (31 medicated) and 40 matched healthy controls were analyzed. Patients displayed enhanced imitation and intact top-down modulation of imitation. The enhanced imitation seen in patients may have been medication induced as larger effects were seen in patients receiving higher antipsychotic doses. In sum, we did not find an imitation impairment in schizophrenia. The results suggest that previous findings of impaired imitation in schizophrenia might have been due to other cognitive, motoric, and/or emotional deficits.

S67. INTEGRATION OF SENSORY AND SOCIAL INFORMATION DURING DECISION MAKING IN SCHIZOPHRENIA

Abstract Background Previous findings suggest that schizophrenia is associated with abnormalities in information integration. The recent Bayesian model of circular inference attempts to characterize the information integration style in schizophrenia (Jardri et al. (2017). Nat Commun, 8:14218). The model suggests that during information integration of prior beliefs and sensory evidence, patients tend to put too much weight on the sensory evidence and to take it into account multiple times (over-count) compared to healthy individuals. An imbalance in excitatory/inhibitory regulation of hierarchical neural processing has been suggested to cause of this phenomenon (Jardri et al., 2017). Here, we investigated whether circular inference could be extended to describe the integration of sensory information and socially acquired information and whether the specific information integration style could contribute to the characteristic symptomatology and the social impairments seen in the disorder. Methods Thirty-five patients with schizophrenia or schizo-affective disorder and 40 matched healthy controls performed the task. Participants had to guess the color (red or green) of the next marble to be drawn from a hidden urn based on information from their own sample (eight marbles) and the choices and confidence (high or low) of four other people. We fitted and comparatively assessed four multilevel Bayesian models (generalized linear model, simple Bayes, weighted Bayes, circular inference) describing how patients and controls integrated information. Positive and negative symptom severity and social functioning were also assessed. Results The circular inference model best described the information integration in both patients and controls (WAIC weight = 1). Patients tended to over-weigh (β = 0.48, 95% CI: 0.30; 0.62) and over-count (β = 0.30, 95% CI: 0.12; 0.47) sensory information and under-weigh (β = -0.29, 95% CI: -0.42; -0.13) and under-count (β = -0.23, 95% CI: -0.35; -0.06) social information compared to controls. Crucially, this varied with symptomatology: the higher the symptom severity, the more over-counting and the higher the weight on sensory information and the more under-counting and the less weight on social information. More weight on social information was associated with higher level of functioning in the patients (β = 0.88, 95% CI: 0.01; 3.73). Discussion All participants integrated social and sensory information in a non-linear fashion. Patients displayed a distinctive tendency to rely more and less discriminatively on sensory than on social information. This information integration style may contribute to the characteristic symptoms and the social impairments in schizophrenia. Further exploration of this potential causal role is warranted.

T138. ACOUSTIC PATTERNS IN SCHIZOPHRENIA: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract Background Individuals with schizophrenia are characterized as presenting atypical voice patterns: poverty of speech, increased pauses, distinctive pitch (mean and variability). Voice atypicalities may play a role in the social impairment experienced by patients, and could constitute a window into motor, cognitive, emotional and social components of the disorder. Indeed, they have already been generally associated with negative symptoms. However, the state of the evidence for atypical voice patterns and their relation to clinical features is uncertain. Studies using clinical rating scales indicate that voice alterations are severe across many voice properties. In contrast, quantitative acoustic studies seem to have found less robust and more variable results limited to specific features. We therefore systematically reviewed the literature quantifying acoustic patterns in schizophrenia, and performed a meta-analysis of the evidence. We aimed at identifying evidence for acoustic markers of schizophrenia and its clinical features, needs for further research and barriers to collective advancements on these issues. Methods We adopted the “PRISMA Statement” guidelines for transparent reporting of a systematic review. The literature search was conducted on Pubmed and Google Scholar (details and pre-registration at https://goo.gl/H1yDpm). Study selection was conducted according to the following inclusion criteria: (a) empirical study, (b) quantification of acoustic features in the vocal production of participants with schizophrenia, (c) sample including at least two individuals with schizophrenia, (d) inclusion of a comparison group, or an assessment of variation in acoustic features in relation to severity of clinical features. We identified 54 studies as eligible for inclusion and contacted all authors to obtain missing estimates and individual-level data, where possible. 34 studies availed enough information to be included in a meta-analysis. The meta-analysis consisted of mixed effects regression models, one per each relevant acoustic feature. Results Of the 37 authors contacted, 59% responded and 5% provided at least some of the requested data. Chief reasons of denials were: i) data loss (n = 8), ii) effort required (n = 5), iii) ethical concerns with data sharing (n = 1). On the results available we found significant meta-analytic effects of schizophrenia in percentage of spoken time (n = 6, d = -1.16, 95% CIs: -2.06 -0.27) and proportion of pauses (n = 5, d = 0.56, 95% CIs: 0.15 0.96). After controlling for influential studies, we found significant differences also in pitch mean (n = 5, d = 0.40, 95% CIs: 0.12 0.68) and pitch variability (n = 6, d = -0.46, 95% CIs: -0.70 -0.23). No effects were found for pause duration (n = 7), speech rate (n = 9), speech duration (n = 5) and pitch intensity (n = 5). We found evidence for publication bias for studies investigating pause duration and pitch variability. Key concerns on the meta-analysis are: i) small sample sizes, ii) heterogeneity of task and acoustic processing methods, iii) lack of demographic and clinical individual-level data necessary to control for confounds (e.g. medication and relation to clinical features). Discussion We found clear effects of increased pause behavior in schizophrenia and less clear effects of pitch. However, the magnitude of these abnormalities is limited and contrast with the large effect sizes reported by studies using clinical rating scales. Future research should focus on larger sample sizes, systematic assessment of multiple acoustic features and multiple speech tasks, standardized acoustic processing methods, and individual level data available. More reflection is needed on how to make data sharing possible within privacy and ethical constraints.