Heart Rate Variability in Children and Adolescents with Autism, ADHD and Co-occurring Autism and ADHD, During Passive and Active Experimental Conditions

Despite overlaps in clinical symptomatology, autism and ADHD may be associated with opposite autonomic arousal profiles which might partly explain altered cognitive and global functioning. We investigated autonomic arousal in 106 children/adolescents with autism, ADHD, co-occurring autism/ADHD, and neurotypical controls. Heart rate variability was recorded during resting-state, a ‘passive’ auditory oddball task and an ‘active’ response conflict task. Autistic children showed hyper-arousal during the active task, while those with ADHD showed hypo-arousal during resting-state and the passive task. Irrespective of diagnosis, children characterised by hyper-arousal showed more severe autistic symptomatology, increased anxiety and reduced global functioning than those displaying hypo-arousal, suggesting the importance of considering individual autonomic arousal profiles for differential diagnosis of autism/ADHD and when developing personalised interventions.

Biological sensitivity to context as a dyadic construct: An investigation of child–parent RSA synchrony among low-SES youth

Parenting behaviors are significantly linked to youths’ behavioral adjustment, an association that is moderated by youths’ and parents’ self-regulation. The biological sensitivity to context theory suggests that respiratory sinus arrhythmia (RSA) indexes youths’ varying susceptibility to rearing contexts. However, self-regulation in the family context is increasingly viewed as a process of “coregulation” that is biologically embedded and involves dynamic Parent×Child interactions. No research thus far has examined physiological synchrony as a dyadic biological context that may moderate associations between parenting behaviors and preadolescent adjustment. Using a two-wave sample of 101 low-socioeconomic status (SES) families (children and caretakers; mean age 10.28 years), we employed multilevel modeling to examine dyadic coregulation during a conflict task, indicated by RSA synchrony, as a moderator of the linkages between observed parenting behaviors and preadolescents’ internalizing and externalizing problems. Results showed that high dyadic RSA synchrony resulted in a multiplicative association between parenting and youth adjustment. High dyadic synchrony intensified the relations between parenting behaviors and youth behavior problems, such that in the context of high dyadic synchrony, positive and negative parenting behaviors were associated with decreased and increased behavioral problems, respectively. Parent–child dyadic RSA synchrony is discussed as a potential biomarker of biological sensitivity in youth.

Pre-trial predictors of conflict response efficacy in human dorsolateral prefrontal cortex

The ability to perform motor actions depends, in part, on the brain's initial state, that is the ensemble firing rate pattern prior to the initiation of action. We hypothesized that the same principle would apply to cognitive functions as well. To test this idea, we examined a unique set of single unit data collected in human dorsolateral prefrontal cortex (dlPFC). Data were collected in a conflict task that interleaves Simon (motor-type) and Eriksen (flanker-type) conflict trials. Variability in pre-trial firing rate predicted the ability to resolve conflict, as inferred from reaction times. Ensemble patterns that predicted faster Simon reaction times overlapped slightly with those predicting Eriksen performance, indicating that the two conflict types are associated with near-orthogonal initial states, and suggesting that there is a weak abstract or amodal conflict preparatory state in this region. These codes became fully orthogonalized in the response state. We interpret these results in light of the initial state and dual-mechanisms of control hypotheses, arguing that the firing patterns in dlPFC immediately preceding the start of the task predispose it for the efficient implementation of cognitive action.

Causal Evidence for Induction of Pessimistic Decision-Making in Primates by the Network of Frontal Cortex and Striosomes

Clinical studies have shown that patients with anxiety disorders exhibited coactivation of limbic cortices and basal ganglia, which together form a large-scale brain network. The mechanisms by which such a large-scale network could induce or modulate anxiety-like states are largely unknown. This article reviews our experimental program in macaques demonstrating a causal involvement of local striatal and frontal cortical sites in inducing pessimistic decision-making that underlies anxiety. Where relevant, we related these findings to the wider literature. To identify such sites, we have made a series of methodologic advances, including the combination of causal evidence for behavioral modification of pessimistic decisions with viral tracing methods. Critically, we introduced a version of the classic approach-avoidance (Ap-Av) conflict task, modified for use in non-human primates. We performed microstimulation of limbic-related cortical regions and the striatum, focusing on the pregenual anterior cingulate cortex (pACC), the caudal orbitofrontal cortex (cOFC), and the caudate nucleus (CN). Microstimulation of localized sites within these regions induced pessimistic decision-making by the monkeys, supporting the idea that the focal activation of these regions could induce an anxiety-like state, which subsequently influences decision-making. We further performed combined microstimulation and tract-tracing experiments by injecting anterograde viral tracers into focal regions, at which microstimulation induced increased avoidance. We found that effective stimulation sites in both pACC and cOFC zones projected preferentially to striosomes in the anterior striatum. Experiments in rodents have shown that the striosomes in the anterior striatum project directly to the dopamine-containing cells in the substantia nigra, and we have found evidence for a functional connection between striosomes and the lateral habenular region in which responses to reward are inhibitory. We present here further evidence for network interactions: we show that the pACC and cOFC project to common structures, including not only the anterior parts of the striosome compartment but also the tail of the CN, the subgenual ACC, the amygdala, and the thalamus. Together, our findings suggest that networks having pACC and cOFC as nodes share similar features in their connectivity patterns. We here hypothesize, based on these results, that the brain sites related to pessimistic judgment are mediated by a large-scale brain network that regulates dopaminergic functions and includes striosomes and striosome-projecting cortical regions.

Gaze-Related Activity in Primate Frontal Cortex Predicts and Mitigates Spatial Uncertainty

A remarkable feature of primate behavior is the ability to predict future events based on past experience and current sensory cues. To understand how the brain plans movements in the presence of unstable cues, we recorded gaze-related activity in the frontal cortex of two monkeys engaged in a quasi-predictable cue-conflict task. Animals were trained to look toward remembered visual targets in the presence of a landmark that shifted with fixed amplitude but randomized direction. As simulated by a probabilistic model based on known physiology/behavior, gaze end points assumed a circular distribution around the target, mirroring the possible directions of the landmark shift. This predictive strategy was reflected in frontal cortex activity (especially supplementary eye fields), which anticipated future gaze distributions before the actual landmark shift. In general, these results implicate prefrontal cortex in the predictive integration of environmental cues and their learned statistical properties to mitigate spatial uncertainty.

Intermodal Priming of Cognitive Conflict? A Failed Replication of Mager et al. (2009)

Introduction: The present study was conducted to verify a promising experimental setup which demonstrated an inversed Stroop-effect (much faster responses for incongruent relative to congruent Stroop trials) following a mismatching tone. In the matching condition, which was an almost exact replication of the original study, participants were required to indicate whether word color and word meaning were matching, whereas in the response conflict condition, instruction was the same as in a classical Stroop task and required the participants to respond to the word color. As in the original study, each trial was preceded by a sine tone which was deviant in pitch in 20% of the trials.Results: The main result was that the Stroop effect was not inversed after deviant tones, neither under the matching task instruction nor under the response conflict task instruction. The Stroop effect was unaffected by the previous “conceptual mismatch.”Conclusion: The current study failed to replicate the astonishing concept of “conflict priming” reported in previous work and does not open the doors for a new window on sequences of conflicts. Nevertheless, the failed replication is valuable for future research, since it demonstrated that “Conflict Priming” as a facilitation of processing of conflict trials following deviant tones, is not an confirmed finding.

Bilingual speakers' enhanced monitoring can slow them down

Performance differences between bilingual and monolingual participants on conflict tasks can be affected by the balance of various sub-processes such as monitoring and stimulus categorisation. Here we investigated the effect of bilingualism on these sub-processes during a conflict task with medium monitoring demand. We examined the behavioural and evoked potentials from a group of bilingual and monolingual speakers during a flanker task with 25% incongruent trials. We analysed behavioural differences by means of averaged response times and ex-Gaussian analyses of response time distributions. For the evoked potentials we focused on the N2 (implicated to be involved in monitoring) and P300 (implicated to be involved in categorisation) responses. We found that bilinguals had significantly longer response distribution tails compared to monolinguals. Additionally, bilinguals exhibited a more pronounced N2 and smaller P3 components compared to their monolingual counterparts, independent of experimental condition, suggesting enhanced monitoring processes and reduced categorisation effort. Importantly, N2 amplitudes were positively and P3 amplitudes were negatively related to the length of response distribution tails. We postulate that these results reflect an overactive monitoring system in bilinguals in a task of medium monitoring demand. This enhanced monitoring leads to less effortful categorisation, but also occasionally to slow responses. These results suggest that changes of the cognitive control system due to bilingual experience changes the balance of processes during conflict tasks, potentially leading to a small behavioural disadvantage.

Conflict Test Battery for Studying the Act of Facing Threats in Pursuit of Rewards

Survival depends on the ability of animals to avoid threats and approach rewards. Traditionally, these two opposing motivational systems have been studied separately. In nature, however, they regularly compete for the control of behavior. When threat- and reward-eliciting stimuli (learned or unlearned) occur simultaneously, a motivational conflict emerges that challenges individuals to weigh available options and execute a single behavioral response (avoid or approach). Most previous animal models using approach/avoidance conflicts have often focused on the ability to avoid threats by forgoing or delaying the opportunity to obtain rewards. In contrast, behavioral tasks designed to capitalize on the ability to actively choose to execute approach behaviors despite threats are scarce. Thus, we developed a behavioral test battery composed of three conflict tasks to directly study rats confronting threats to obtain rewards guided by innate and conditioned cues. One conflict task involves crossing a potentially electrified grid to obtain food on the opposite end of a straight alley, the second task is based on the step-down threat avoidance paradigm, and the third one is a modified version of the open field test. We used diazepam to pharmacologically validate conflict behaviors in our tasks. We found that, regardless of whether competing stimuli were conditioned or innate, a low diazepam dose decreased risk assessment and facilitated taking action to obtain rewards in the face of threats during conflict, without affecting choice behavior when there was no conflict involved. Using this pharmacologically validated test battery of ethologically designed innate/learned conflict tasks could help understand the fundamental brain mechanisms underlying the ability to confront threats to achieve goals.

Real-world stress resilience is associated with the responsivity of the locus coeruleus

Individuals may show different responses to stressful events. Here, we investigate the neurobiological basis of stress resilience, by showing that neural responsitivity of the noradrenergic locus coeruleus (LC-NE) and associated pupil responses are related to the subsequent change in measures of anxiety and depression in response to prolonged real-life stress. We acquired fMRI and pupillometry data during an emotional-conflict task in medical residents before they underwent stressful emergency-room internships known to be a risk factor for anxiety and depression. The LC-NE conflict response and its functional coupling with the amygdala was associated with stress-related symptom changes in response to the internship. A similar relationship was found for pupil-dilation, a potential marker of LC-NE firing. Our results provide insights into the noradrenergic basis of conflict generation, adaptation and stress resilience.

Systematically Defined Informative Priors in Bayesian Estimation: An Empirical Application on the Transmission of Internalizing Symptoms Through Mother-Adolescent Interaction Behavior

BackgroundBayesian estimation with informative priors permits updating previous findings with new data, thus generating cumulative knowledge. To reduce subjectivity in the process, the present study emphasizes how to systematically weigh and specify informative priors and highlights the use of different aggregation methods using an empirical example that examined whether observed mother-adolescent positive and negative interaction behavior mediate the associations between maternal and adolescent internalizing symptoms across early to mid-adolescence in a 3-year longitudinal multi-method design.MethodsThe sample consisted of 102 mother-adolescent dyads (39.2% girls, Mage T1 = 13.0). Mothers and adolescents reported on their internalizing symptoms and their interaction behaviors were observed during a conflict task. We systematically searched for previous studies and used an expert-informed weighting system to account for their relevance. Subsequently, we aggregated the (power) priors using three methods: linear pooling, logarithmic pooling, and fitting a normal distribution to the linear pool by means of maximum likelihood estimation. We compared the impact of the three differently specified informative priors and default priors on the prior predictive distribution, shrinkage, and the posterior estimates.ResultsThe prior predictive distributions for the three informative priors were quite similar and centered around the observed data mean. The shrinkage results showed that the logarithmic pooled priors were least affected by the data. Most posterior estimates were similar across the different priors. Some previous studies contained extremely specific information, resulting in bimodal posterior distributions for the analyses with linear pooled prior distributions. The posteriors following the fitted normal priors and default priors were very similar. Overall, we found that maternal, but not adolescent, internalizing symptoms predicted subsequent mother-adolescent interaction behavior, whereas negative interaction behavior seemed to predict subsequent internalizing symptoms. Evidence regarding mediation effects remained limited.ConclusionA systematic search for previous information and an expert-built weighting system contribute to a clear specification of power priors. How information from multiple previous studies should be included in the prior depends on theoretical considerations (e.g., the prior is an updated Bayesian distribution), and may also be affected by pragmatic considerations regarding the impact of the previous results at hand (e.g., extremely specific previous results).