The effects of tryptophan loading on Attention Deficit Hyperactivity in adults: A remote double blind randomised controlled trial.

BACKGROUND: Despite the impact and prevalence of Attention Deficit Hyperactivity Disorder (ADHD), current treatment options remain limited and there is a drive for alternative approaches, including those building on evidence of a role for tryptophan (TRP) and serotonin (5-HT). This study aimed to evaluate the effect of acute TRP loading on attention and impulsivity in adults with ADHD. TRIAL DESIGN AND METHODS: We conducted a remote double blind randomised controlled trial (RCT) using TRP loading to examine the effects of a balanced amino acid load in comparison to low and high TRP loading in individuals with ADHD (medicated, N = 48, and unmedicated, N = 46) and controls (N = 50). Participants were randomised into one of three TRP treatment groups using stratified randomisation considering participant group and gender using a 1:1:1 ratio. Baseline testing of attention and impulsivity using the Test of Variables of Attention Task, Delay Discounting Task, and Iowa Gambling Task was followed by consumption of a protein drink (BAL, LOW, or HIGH TRP) before repeated testing. RESULTS AND CONCLUSIONS: No effects of TRP were observed for any of the measures. In the present study, TRP loading did not impact on any measure of attention or impulsivity in those with ADHD or Controls. The findings need to be confirmed in another trial with a larger number of patients that also considers additional measures of dietary protein, plasma TRP and aggression. (Registration ID ISRCTN15119603).

Measuring trust with the Wayfinding Task: Implementing a novel task in immersive virtual reality and desktop setups across remote and in-person test environments.

Trust is a key feature of social relationships. Common measures of trust, questionnaires and economic games, lack ecological validity. Hence, we sought to introduce an immersive, virtual reality (VR) measure for the behavioral assessment of trust across remote and in-person settings, building on the maze task of Hale et al. (2018). Our 'Wayfinding Task' consists of an interconnected urban environment for participants to navigate on the advice of two characters of differing trustworthiness. We present four studies implementing the Wayfinding Task in remote and in-person testing environments and comparing performance across head-mounted display (HMD)-based VR and desktop setups. In each study, the trustworthiness of two virtual characters was manipulated, through either a fact sheet providing trustworthiness information, or a behavior-based trustworthiness manipulation task termed the Door Game, based on Van der Biest et al., 2020. Participants then completed the Wayfinding Task. Overall, we found that participant behavior in the Wayfinding Task reflected the relative trustworthiness of the two characters; in particular, the trustworthy character was approached more often for advice, reflecting data from our Door Game. We found mostly null results for our novel outcome measure, interpersonal distance. Remote testing successfully achieved these effects. While HMD-based VR and desktop setups both showed these effects, there was a stronger effect of trustworthiness in the HMD VR version of the task. These results have implications for the measurement of trust in behavioral settings and the use of remote and VR-based testing in social experiments.

The Effects of Different Exercise Approaches on Attention Deficit Hyperactivity Disorder in Adults: A Randomised Controlled Trial.

Attention deficit hyperactivity disorder (ADHD) results in significant functional impairment. Current treatments, particularly for adults, are limited. Previous research indicates that exercise may offer an alternative approach to managing ADHD, but research into different types of exercise and adult populations is limited. The aim of this study was to examine the effects of acute exercise (aerobic cycling vs mind-body yoga exercises) on symptoms of ADHD in adults. Adults with ADHD (N = 82) and controls (N = 77) were randomly allocated to 10 min of aerobic (cycling) or mind-body (Hatha yoga) exercise. Immediately before and after exercise, participants completed the Test of Variables of Attention task, Delay Discounting Task, and Iowa Gambling Task to measure attention and impulsivity. Actigraphy measured movement frequency and intensity. Both groups showed improved temporal impulsivity post-exercise, with cycling beneficial to all, whilst yoga only benefited those with ADHD. There were no effects of exercise on attention, cognitive or motor impulsivity, or movement in those with ADHD. Exercise reduced attention and increased movement in controls. Exercise can improve temporal impulsivity in adult ADHD but did not improve other symptoms and worsened some aspects of performance in controls. Exercise interventions should be further investigated.

Event timing in human vision: Modulating factors and independent functions.

Essential for successful interaction with the environment is the human capacity to resolve events in time. Typical event timing paradigms are judgements of simultaneity (SJ) and of temporal order (TOJ). It remains unclear whether SJ and TOJ are based on the same underlying mechanism and whether there are fixed thresholds for resolution. The current study employed four visual event timing task versions: horizontal and vertical SJ and TOJ. Binary responses were analysed using multilevel binary regression modelling. Modulatory effects of potential explanatory variables on event timing perception were investigated: (1) Individual factors (sex and age), (2) temporal factors (SOA, trial number, order of experiment, order of stimuli orientation, time of day) and (3) spatial factors (left or right stimulus first, top or bottom stimulus first, horizontal vs. vertical orientation). The current study directly compares for the first time, performance on SJ and TOJ tasks using the same paradigm and presents evidence that a variety of factors and their interactions selectively modulate event timing functions in humans, explaining the variance found in previous studies. We conclude that SJ and TOJ are partially independent functions, because they are modulated differently by individual and contextual variables.

Distinct neural correlates of social and object reward seeking motivation.

The "Choose-a-Movie-CAM" is an established task to quantify the motivation for seeking social rewards. It allows participants to directly assess both the stimulus value and the effort required to obtain it. In the present study, we aimed to identify the neural mechanisms of such cost-benefit decision-making. To this end, functional Magnetic Resonance Imaging data were collected from 24 typical adults while they completed the CAM task. We partly replicated the results from our previous behavioural studies showing that typical adults prefer social over object stimuli and low effort over higher effort stimuli but found no interaction between the two. Results from neuroimaging data suggest that there are distinct neural correlates for social and object preferences. The precuneus and medial orbitofrontal cortex, two key areas involved in social processing are engaged when participants make a social choice. Areas of the ventral and dorsal stream pathways associated with object recognition are engaged when making an object choice. These activations can be seen during the decision phase even before the rewards have been consumed, indicating a transfer the hedonic properties of social stimuli to its cues. We also found that the left insula and bilateral clusters in the inferior occipital gyrus and the inferior parietal lobule were recruited for increasing effort investment. We discuss limitations and implications of this study which reveals the distinct neural correlates for social and object rewards, using a robust behavioural measure of social motivation.

INTRApersonal Synchrony as Constituent of INTERpersonal Synchrony and Its Relevance for Autism Spectrum Disorder.

INTERpersonal synchrony leads to increased empathy, rapport and understanding, enabling successful human-human interactions and reciprocal bonding. Research shows that individuals with Autism Spectrum Disorder (ASD) exhibit difficulties to INTERpersonally synchronize but underlying causes are yet unknown. In order to successfully synchronize with others, INTRApersonal synchronization of communicative signals appears to be a necessary prerequisite. We understand INTRApersonal synchrony as an implicit factor of INTERpersonal synchrony and therefore hypothesize that atypicalities of INTRApersonal synchrony may add to INTERpersonal synchrony problems in ASD and their interaction partners. In this perspective article, we first review evidence for INTERpersonal dissynchrony in ASD, with respect to different approaches and assessment methods. Second, we draft a theoretical conceptualization of INTRApersonal dissynchrony in ASD based on a temporal model of human interaction. We will outline literature indicating INTRApersonal dissynchrony in ASD, therefore highlighting findings of atypical timing functions and findings from clinical and behavioral studies that indicate peculiar motion patterns and communicative signal production in ASD. Third, we hypothesize that findings from these domains suggest an assessment and investigation of temporal parameters of social behavior in individuals with ASD. We will further propose specific goals of empirical approaches on INTRApersonal dissynchrony. Finally we present implications of research on INTRApersonal timing in ASD for diagnostic and therapeutic purposes, what in our opinion warrants the increase of research efforts in this domain.

Adults with autism spectrum condition have atypical perception of ambiguous figures when bottom-up and top-down interactions are incongruous.

We examined the perception of an ambiguous squares stimulus evoking bistable perception in a sample of 31 individuals with autistic spectrum condition and 22 matched typical adults. The perception of the ambiguous figure was manipulated by adaptation to unambiguous figures and/or by placing the ambiguous figure into a context of unambiguous figures. This resulted in four conditions testing the independent and combined (congruent and incongruent) manipulations of adaptation (bottom-up) and spatial context (top-down) effects. The strength of perception, as measured by perception of the first reported orientation of the ambiguous stimulus, was affected comparably between groups. Nevertheless, the strength of perception, as measured by perceptual durations, was affected differently between groups: the perceptual effect was strongest for the autistic spectrum condition group when combined bottom-up and top-down conditions were congruent. In contrast, the strength of the perceptual effect in response to the same condition in the typical adults group was comparable to the adaptation, but stronger than both the context and the incongruent combined bottom-up and top-down conditions. Furthermore, the context condition was stronger than the incongruent combined bottom-up and top-down conditions for the typical adults group. Thus, our findings support the view of stimulus-specific top-down modulation in autistic spectrum condition.

Absence of sex differences in mental rotation performance in autism spectrum disorder.

Mental rotation is one of the most investigated cognitive functions showing consistent sex differences. The 'Extreme Male Brain' hypothesis attributes the cognitive profile of individuals with autism spectrum disorder to an extreme version of the male cognitive profile. Previous investigations focused almost exclusively on males with autism spectrum disorder with only limited implications for affected females. This study is the first testing a sample of 12 female adults with high-functioning autism spectrum disorder compared to 14 males with autism spectrum disorder, 12 typically developing females and 14 typically developing males employing a computerised version of the mental rotation test. Reaction time and accuracy served as dependent variables. Their linear relationship with degree of rotation allows separation of rotational aspects of the task, indicated by slopes of the psychometric function, and non-rotational aspects, indicated by intercepts of the psychometric function. While the typical and expected sex difference for rotational task aspects was corroborated in typically developing individuals, no comparable sex difference was found in autism spectrum disorder individuals. Autism spectrum disorder and typically developing individuals did not differ in mental rotation performance. This finding does not support the extreme male brain hypothesis of autism.

Why we interact: on the functional role of the striatum in the subjective experience of social interaction.

There is ample evidence that human primates strive for social contact and experience interactions with conspecifics as intrinsically rewarding. Focusing on gaze behavior as a crucial means of human interaction, this study employed a unique combination of neuroimaging, eye-tracking, and computer-animated virtual agents to assess the neural mechanisms underlying this component of behavior. In the interaction task, participants believed that during each interaction the agent's gaze behavior could either be controlled by another participant or by a computer program. Their task was to indicate whether they experienced a given interaction as an interaction with another human participant or the computer program based on the agent's reaction. Unbeknownst to them, the agent was always controlled by a computer to enable a systematic manipulation of gaze reactions by varying the degree to which the agent engaged in joint attention. This allowed creating a tool to distinguish neural activity underlying the subjective experience of being engaged in social and non-social interaction. In contrast to previous research, this allows measuring neural activity while participants experience active engagement in real-time social interactions. Results demonstrate that gaze-based interactions with a perceived human partner are associated with activity in the ventral striatum, a core component of reward-related neurocircuitry. In contrast, interactions with a computer-driven agent activate attention networks. Comparisons of neural activity during interaction with behaviorally naïve and explicitly cooperative partners demonstrate different temporal dynamics of the reward system and indicate that the mere experience of engagement in social interaction is sufficient to recruit this system.

Dissociating animacy processing in high-functioning autism: neural correlates of stimulus properties and subjective ratings.

When movements indicate meaningful actions, even nonbiological objects induce the impression of "having a mind" or animacy. This basic social ability was investigated in adults with high-functioning autism (HFA, n = 13, and matched controls, n = 13) by systematically varying motion properties of simple geometric shapes. Critically, trial-by-trial variations of (1) motion complexity of stimuli, and of (2) participants' individual animacy ratings were separately correlated with neural activity to dissociate cognitive strategies relying more closely on stimulus analysis vs. subjective experience. Increasing motion complexity did not yield any significant group differences, and in both groups, it correlated with neural activity in regions involved in perceptual and evaluative processing, including the ventral medial prefrontal cortex (mPFC), superior temporal gyrus (STG) and posterior cingulate cortex (PCC). In contrast, although there were no significant behavioral differences between the groups, increasing animacy ratings correlated with neural activity in the insula, STG, amygdala, dorsal mPFC and PCC more strongly in controls than in HFA. These results indicate that in HFA the evaluation of stimulus properties cuing for animacy is intact, while increasing subjective ratings do not seem to be robustly related to social processing, including spontaneous mental state inferences and experience of salience.

Perceiving nonverbal behavior: neural correlates of processing movement fluency and contingency in dyadic interactions.

Despite the fact that nonverbal dyadic social interactions are abundant in the environment, the neural mechanisms underlying their processing are not yet fully understood. Research in the field of social neuroscience has suggested that two neural networks appear to be involved in social understanding: (1) the action observation network (AON) and (2) the social neural network (SNN). The aim of this study was to determine the differential contributions of the AON and the SNN to the processing of nonverbal behavior as observed in dyadic social interactions. To this end, we used short computer animation sequences displaying dyadic social interactions between two virtual characters and systematically manipulated two key features of movement activity, which are known to influence the perception of meaning in nonverbal stimuli: (1) movement fluency and (2) contingency of movement patterns. A group of 21 male participants rated the "naturalness" of the observed scenes on a four-point scale while undergoing fMRI. Behavioral results showed that both fluency and contingency significantly influenced the "naturalness" experience of the presented animations. Neurally, the AON was preferentially engaged when processing contingent movement patterns, but did not discriminate between different degrees of movement fluency. In contrast, regions of the SNN were engaged more strongly when observing dyads with disturbed movement fluency. In conclusion, while the AON is involved in the general processing of contingent social actions, irrespective of their kinematic properties, the SNN is preferentially recruited when atypical kinematic properties prompt inferences about the agents' intentions.

Duration matters: dissociating neural correlates of detection and evaluation of social gaze.

The interpretation of interpersonal gaze behavior requires the use of complex cognitive processes and guides social interactions. Among a variety of different gaze characteristics, gaze direction and gaze duration modulate crucially the meaning of the "social gaze". Nevertheless, prior neuroimaging studies disregarded the relevance of gaze duration by focusing on gaze direction only. The present functional magnetic resonance imaging (fMRI) study focused on the differentiation of these two gaze parameters. Therefore direct gaze displayed by virtual characters was contrasted with averted gaze and, additionally, systematically varied with respect to gaze duration (i.e., 1, 2.5 or 4 s). Consistent with prior findings, behavioral data showed that likeability was higher for direct than for averted gaze and increased linearly with increasing direct gaze duration. On the neural level, distinct brain regions were associated with the processing of gaze direction and gaze duration: (i) the comparison between direct and averted gaze revealed activations in bilateral occipito-temporal regions including the posterior superior temporal sulcus (pSTS); (ii) whereas increasing duration of direct gaze evoked differential neural responses in the medial prefrontal cortex (MPFC) including orbitofrontal and paracingulate regions. The results suggest two complementary cognitive processes related to different gaze parameters. On the one hand, the recruitment of multimodal sensory regions in the pSTS indicates detection of gaze direction via complex visual analysis. On the other hand, the involvement of the MPFC associated with outcome monitoring and mentalizing indicates higher-order social cognitive processes related to evaluation of the ongoing communicational input conveyed by direct gaze duration.