Reconstructing computational system dynamics from neural data with recurrent neural networks.

Computational models in neuroscience usually take the form of systems of differential equations. The behaviour of such systems is the subject of dynamical systems theory. Dynamical systems theory provides a powerful mathematical toolbox for analysing neurobiological processes and has been a mainstay of computational neuroscience for decades. Recently, recurrent neural networks (RNNs) have become a popular machine learning tool for studying the non-linear dynamics of neural and behavioural processes by emulating an underlying system of differential equations. RNNs have been routinely trained on similar behavioural tasks to those used for animal subjects to generate hypotheses about the underlying computational mechanisms. By contrast, RNNs can also be trained on the measured physiological and behavioural data, thereby directly inheriting their temporal and geometrical properties. In this way they become a formal surrogate for the experimentally probed system that can be further analysed, perturbed and simulated. This powerful approach is called dynamical system reconstruction. In this Perspective, we focus on recent trends in artificial intelligence and machine learning in this exciting and rapidly expanding field, which may be less well known in neuroscience. We discuss formal prerequisites, different model architectures and training approaches for RNN-based dynamical system reconstructions, ways to evaluate and validate model performance, how to interpret trained models in a neuroscience context, and current challenges.

Formalizing psychological interventions through network control theory.

Despite the growing deployment of network representation to comprehend psychological phenomena, the question of whether and how networks can effectively describe the effects of psychological interventions remains elusive. Network control theory, the engineering study of networked interventions, has recently emerged as a viable methodology to characterize and guide interventions. However, there is a scarcity of empirical studies testing the extent to which it can be useful within a psychological context. In this paper, we investigate a representative psychological intervention experiment, use network control theory to model the intervention and predict its effect. Using this data, we showed that: (1) the observed psychological effect, in terms of sensitivity and specificity, relates to the regional network control theoretic metrics (average and modal controllability), (2) the size of change following intervention negatively correlates with a whole-network topology that quantifies the "ease" of change as described by control theory (control energy), and (3) responses after intervention can be predicted based on formal results from control theory. These insights assert that network control theory has significant potential as a tool for investigating psychological interventions. Drawing on this specific example and the overarching framework of network control theory, we further elaborate on the conceptualization of psychological interventions, methodological considerations, and future directions in this burgeoning field.

Artificial intelligence-informed mobile mental health apps for young people: a mixed-methods approach on users' and stakeholders' perspectives.

BACKGROUND: Novel approaches in mobile mental health (mHealth) apps that make use of Artificial Intelligence (AI), Ecological Momentary Assessments, and Ecological Momentary Interventions have the potential to support young people in the achievement of mental health and wellbeing goals. However, little is known on the perspectives of young people and mental health experts on this rapidly advancing technology. This study aims to investigate the subjective needs, attitudes, and preferences of key stakeholders towards an AI-informed mHealth app, including young people and experts on mHealth promotion and prevention in youth. METHODS: We used a convergent parallel mixed-method study design. Two semi-structured online focus groups (n = 8) and expert interviews (n = 5) to explore users and stakeholders perspectives were conducted. Furthermore a representative online survey was completed by young people (n = 666) to investigate attitudes, current use and preferences towards apps for mental health promotion and prevention. RESULTS: Survey results show that more than two-thirds of young people have experience with mHealth apps, and 60% make regular use of 1-2 apps. A minority (17%) reported to feel negative about the application of AI in general, and 19% were negative about the embedding of AI in mHealth apps. This is in line with qualitative findings, where young people displayed rather positive attitudes towards AI and its integration into mHealth apps. Participants reported pragmatic attitudes towards data sharing and safety practices, implying openness to share data if it adds value for users and if the data request is not too intimate, however demanded transparency of data usage and control over personalization. Experts perceived AI-informed mHealth apps as a complementary solution to on-site delivered interventions in future health promotion among young people. Experts emphasized opportunities in regard with low-threshold access through the use of smartphones, and the chance to reach young people in risk situations. CONCLUSIONS: The findings of this exploratory study highlight the importance of further participatory development of training components prior to implementation of a digital mHealth training in routine practice of mental health promotion and prevention. Our results may help to guide developments based on stakeholders' first recommendations for an AI-informed mHealth app.

Comparing Discounting of Potentially Real Rewards and Losses by Means of Functional Magnetic Resonance Imaging.

Aim: Delay discounting (DD) has often been investigated in the context of decision making whereby individuals attribute decreasing value to rewards in the distant future. Less is known about DD in the context of negative consequences. The aim of this pilot study was to identify commonalities and differences between reward and loss discounting on the behavioral as well as the neural level by means of computational modeling and functional Magnetic Resonance Imaging (fMRI). We furthermore compared the neural activation between anticipation of rewards and losses. Method: We conducted a study combining an intertemporal choice task for potentially real rewards and losses (decision-making) with a monetary incentive/loss delay task (reward/loss anticipation). Thirty healthy participants (age 18-35, 14 female) completed the study. In each trial, participants had to choose between a smaller immediate loss/win and a larger loss/win at a fixed delay of two weeks. Task-related brain activation was measured with fMRI. Results: Hyperbolic discounting parameters of loss and reward conditions were correlated (r = 0.56). During decision-making, BOLD activation was observed in the parietal and prefrontal cortex, with no differences between reward and loss conditions. During reward and loss anticipation, dissociable activation was observed in the striatum, the anterior insula and the anterior cingulate cortex. Conclusion: We observed behavior concurrent with DD in both the reward and loss condition, with evidence for similar behavioral and neural patterns in the two conditions. Intertemporal decision-making recruited the fronto-parietal network, whilst reward and loss anticipation were related to activation in the salience network. The interpretation of these findings may be limited to short delays and small monetary outcomes.

A Model Guided Approach to Evoke Homogeneous Behavior During Temporal Reward and Loss Discounting.

Background: The tendency to devaluate future options as a function of time, known as delay discounting, is associated with various factors such as psychiatric illness and personality. Under identical experimental conditions, individuals may therefore strongly differ in the degree to which they discount future options. In delay discounting tasks, this inter-individual variability inevitably results in an unequal number of discounted trials per subject, generating difficulties in linking delay discounting to psychophysiological and neural correlates. Many studies have therefore focused on assessing delay discounting adaptively. Here, we extend these approaches by developing an adaptive paradigm which aims at inducing more comparable and homogeneous discounting frequencies across participants on a dimensional scale. Method: The proposed approach probabilistically links a (common) discounting function to behavior to obtain a probabilistic model, and then exploits the model to obtain a formal condition which defines how to construe experimental trials so as to induce any desired discounting probability. We first infer subject-level models on behavior on a non-adaptive delay discounting task and then use these models to generate adaptive trials designed to evoke graded relative discounting frequencies of 0.3, 0.5, and 0.7 in each participant. We further compare and evaluate common models in the field through out-of-sample prediction error estimates, to iteratively improve the trial-generating model and paradigm. Results: The developed paradigm successfully increases discounting behavior during both reward and loss discounting. Moreover, it evokes graded relative choice frequencies in line with model-based expectations (i.e., 0.3, 0.5, and 0.7) suggesting that we can successfully homogenize behavior. Our model comparison analyses indicate that hyperboloid models are superior in predicting unseen discounting behavior to more conventional hyperbolic and exponential models. We report out-of-sample error estimates as well as commonalities and differences between reward and loss discounting, demonstrating for instance lower discounting rates, as well as differences in delay perception in loss discounting. Conclusion: The present work proposes a model-based framework to evoke graded responses linked to cognitive function at a single subject level. Such a framework may be used in the future to measure cognitive functions on a dimensional rather than dichotomous scale.

Classification of amyotrophic lateral sclerosis by brain volume, connectivity, and network dynamics.

Emerging studies corroborate the importance of neuroimaging biomarkers and machine learning to improve diagnostic classification of amyotrophic lateral sclerosis (ALS). While most studies focus on structural data, recent studies assessing functional connectivity between brain regions by linear methods highlight the role of brain function. These studies have yet to be combined with brain structure and nonlinear functional features. We investigate the role of linear and nonlinear functional brain features, and the benefit of combining brain structure and function for ALS classification. ALS patients (N = 97) and healthy controls (N = 59) underwent structural and functional resting state magnetic resonance imaging. Based on key hubs of resting state networks, we defined three feature sets comprising brain volume, resting state functional connectivity (rsFC), as well as (nonlinear) resting state dynamics assessed via recurrent neural networks. Unimodal and multimodal random forest classifiers were built to classify ALS. Out-of-sample prediction errors were assessed via five-fold cross-validation. Unimodal classifiers achieved a classification accuracy of 56.35-61.66%. Multimodal classifiers outperformed unimodal classifiers achieving accuracies of 62.85-66.82%. Evaluating the ranking of individual features' importance scores across all classifiers revealed that rsFC features were most dominant in classification. While univariate analyses revealed reduced rsFC in ALS patients, functional features more generally indicated deficits in information integration across resting state brain networks in ALS. The present work undermines that combining brain structure and function provides an additional benefit to diagnostic classification, as indicated by multimodal classifiers, while emphasizing the importance of capturing both linear and nonlinear functional brain properties to identify discriminative biomarkers of ALS.

Model-based experimental manipulation of probabilistic behavior in interpretable behavioral latent variable models.

Introduction: Interpretable latent variable models that probabilistically link behavioral observations to an underlying latent process have increasingly been used to draw inferences on cognition from observed behavior. The latent process usually connects experimental variables to cognitive computation. While such models provide important insights into the latent processes generating behavior, one important aspect has often been overlooked. They may also be used to generate precise and falsifiable behavioral predictions as a function of the modeled experimental variables. In doing so, they pinpoint how experimental conditions must be designed to elicit desired behavior and generate adaptive experiments. Methods: These ideas are exemplified on the process of delay discounting (DD). After inferring DD models from behavior on a typical DD task, the models are leveraged to generate a second adaptive DD task. Experimental trials in this task are designed to elicit 9 graded behavioral discounting probabilities across participants. Models are then validated and contrasted to competing models in the field by assessing the ouf-of-sample prediction error. Results: The proposed framework induces discounting probabilities on nine levels. In contrast to several alternative models, the applied model exhibits high validity as indicated by a comparably low prediction error. We also report evidence for inter-individual differences with respect to the most suitable models underlying behavior. Finally, we outline how to adapt the proposed method to the investigation of other cognitive processes including reinforcement learning. Discussion: Inducing graded behavioral frequencies with the proposed framework may help to highly resolve the underlying cognitive construct and associated neuronal substrates.

Artificial intelligence applications in social media for depression screening: A systematic review protocol for content validity processes.

BACKGROUND: The popularization of social media has led to the coalescing of user groups around mental health conditions; in particular, depression. Social media offers a rich environment for contextualizing and predicting users' self-reported burden of depression. Modern artificial intelligence (AI) methods are commonly employed in analyzing user-generated sentiment on social media. In the forthcoming systematic review, we will examine the content validity of these computer-based health surveillance models with respect to standard diagnostic frameworks. Drawing from a clinical perspective, we will attempt to establish a normative judgment about the strengths of these modern AI applications in the detection of depression. METHODS: We will perform a systematic review of English and German language publications from 2010 to 2020 in PubMed, APA PsychInfo, Science Direct, EMBASE Psych, Google Scholar, and Web of Science. The inclusion criteria span cohort, case-control, cross-sectional studies, randomized controlled studies, in addition to reports on conference proceedings. The systematic review will exclude some gray source materials, specifically editorials, newspaper articles, and blog posts. Our primary outcome is self-reported depression, as expressed on social media. Secondary outcomes will be the types of AI methods used for social media depression screen, and the clinical validation procedures accompanying these methods. In a second step, we will utilize the evidence-strengthening Population, Intervention, Comparison, Outcomes, Study type (PICOS) tool to refine our inclusion and exclusion criteria. Following the independent assessment of the evidence sources by two authors for the risk of bias, the data extraction process will culminate in a thematic synthesis of reviewed studies. DISCUSSION: We present the protocol for a systematic review which will consider all existing literature from peer reviewed publication sources relevant to the primary and secondary outcomes. The completed review will discuss depression as a self-reported health outcome in social media material. We will examine the computational methods, including AI and machine learning techniques which are commonly used for online depression surveillance. Furthermore, we will focus on standard clinical assessments, as indicating content validity, in the design of the algorithms. The methodological quality of the clinical construct of the algorithms will be evaluated with the COnsensus-based Standards for the selection of health status Measurement Instruments (COSMIN) framework. We conclude the study with a normative judgment about the current application of AI to screen for depression on social media. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register of Systematic Reviews PROSPERO (registration number CRD42020187874).

Social isolation, mental health, and use of digital interventions in youth during the COVID-19 pandemic: A nationally representative survey.

BACKGROUND: Public health measures to curb SARS-CoV-2 transmission rates may have negative psychosocial consequences in youth. Digital interventions may help to mitigate these effects. We investigated the associations between social isolation, COVID-19-related cognitive preoccupation, worries, and anxiety, objective social risk indicators, and psychological distress, as well as use of, and attitude toward, mobile health (mHealth) interventions in youth. METHODS: Data were collected as part of the "Mental Health And Innovation During COVID-19 Survey"-a cross-sectional panel study including a representative sample of individuals aged 16-25 years (N = 666; Mage = 21.3; assessment period: May 5, 2020 to May 16, 2020). RESULTS: Overall, 38% of youth met criteria for moderate or severe psychological distress. Social isolation worries and anxiety, and objective risk indicators were associated with psychological distress, with evidence of dose-response relationships for some of these associations. For instance, psychological distress was progressively more likely to occur as levels of social isolation increased (reporting "never" as reference group: "occasionally": adjusted odds ratio [aOR] 9.1, 95% confidence interval [CI] 4.3-19.1, p < 0.001; "often": aOR 22.2, CI 9.8-50.2, p < 0.001; "very often": aOR 42.3, CI 14.1-126.8, p < 0.001). There was evidence that psychological distress, worries, and anxiety were associated with a positive attitude toward using mHealth interventions, whereas psychological distress, worries, and anxiety were associated with actual use. CONCLUSIONS: Public health measures during pandemics may be associated with poor mental health outcomes in youth. Evidence-based digital interventions may help mitigate the negative psychosocial impact without risk of viral infection given there is an objective need and subjective demand.

Psychiatric Illnesses as Disorders of Network Dynamics.

This review provides a dynamical systems perspective on mental illness. After a brief introduction to the theory of dynamical systems, we focus on the common assumption in theoretical and computational neuroscience that phenomena at subcellular, cellular, network, cognitive, and even societal levels could be described and explained in terms of dynamical systems theory. As such, dynamical systems theory may also provide a framework for understanding mental illnesses. The review examines a number of core dynamical systems phenomena and relates each of these to aspects of mental illnesses. This provides an outline of how a broad set of phenomena in serious and common mental illnesses and neurological conditions can be understood in dynamical systems terms. It suggests that the dynamical systems level may provide a central, hublike level of convergence that unifies and links multiple biophysical and behavioral phenomena in the sense that diverse biophysical changes can give rise to the same dynamical phenomena and, vice versa, similar changes in dynamics may yield different behavioral symptoms depending on the brain area where these changes manifest. We also briefly outline current methodological approaches for inferring dynamical systems from data such as electroencephalography, functional magnetic resonance imaging, or self-reports, and we discuss the implications of a dynamical view for the diagnosis, prognosis, and treatment of psychiatric conditions. We argue that a consideration of dynamics could play a potentially transformative role in the choice and target of interventions.

Deep learning for small and big data in psychiatry.

Psychiatry today must gain a better understanding of the common and distinct pathophysiological mechanisms underlying psychiatric disorders in order to deliver more effective, person-tailored treatments. To this end, it appears that the analysis of 'small' experimental samples using conventional statistical approaches has largely failed to capture the heterogeneity underlying psychiatric phenotypes. Modern algorithms and approaches from machine learning, particularly deep learning, provide new hope to address these issues given their outstanding prediction performance in other disciplines. The strength of deep learning algorithms is that they can implement very complicated, and in principle arbitrary predictor-response mappings efficiently. This power comes at a cost, the need for large training (and test) samples to infer the (sometimes over millions of) model parameters. This appears to be at odds with the as yet rather 'small' samples available in psychiatric human research to date (n < 10,000), and the ambition of predicting treatment at the single subject level (n = 1). Here, we aim at giving a comprehensive overview on how we can yet use such models for prediction in psychiatry. We review how machine learning approaches compare to more traditional statistical hypothesis-driven approaches, how their complexity relates to the need of large sample sizes, and what we can do to optimally use these powerful techniques in psychiatric neuroscience.

Aberrant probabilistic reinforcement learning in first-degree relatives of individuals with bipolar disorder.

BACKGROUND: Motivational dysregulation represents a core vulnerability factor for bipolar disorder. Whether this also comprises aberrant learning of stimulus-reinforcer contingencies is less clear. METHODS: To answer this question, we compared healthy first-degree relatives of individuals with bipolar disorder (n = 42) known to convey an increased risk of developing a bipolar spectrum disorder and healthy individuals (n = 97). Further, we investigated the effects of the behavioral activation system (BAS) on reinforcement learning across the entire sample. All participants were assessed with a probabilistic learning task that distinguishes learning from positive and negative feedback. Main outcome measures included choice frequencies and learning rate parameters generated by computational reinforcement learning algorithms. RESULTS: First-degree relatives choose more rewarding stimuli more consistently and showed marginally reduced learning rates from unexpected negative feedback. Further, first-degree relatives had lower BAS scores than controls, which were negatively associated with learning rates from unexpected negative feedback. LIMITATIONS: However as probands also reported other mental disorders such as Attention-Deficit/Hyperactivity Disorder and substance abuse among their first-degree relatives, we cannot know, whether these findings are specific to the risk for bipolar disorder. CONCLUSION: The behavior of first-degree relatives of individuals with bipolar disorder, who also display increased BAS sensitivity, is less influenced by unexpected negative feedback. This reduced learning from unexpected negative feedback biases subsequent choices towards stimuli with higher probabilities for a reward. In sum, our results confirm the role of aberrant reinforcement learning in the pathophysiology of bipolar disorder.

Influence of Severity of Type and Timing of Retrospectively Reported Childhood Maltreatment on Female Amygdala and Hippocampal Volume.

Deleterious effects of adverse childhood experiences (ACE) on human brain volume are widely reported. First evidence points to differential effects of ACE on brain volume in terms of timing of ACE. Upcoming studies additionally point towards the impact of different types (i.e., neglect and abuse) of ACE in terms of timing. The current study aimed to investigate the correlation between retrospectively reported severity of type (i.e., the extent to which subjects were exposed to abuse and/or neglect, respectively) and timing of ACE on female brain volume in a sample of prolonged traumatized subjects. A female sample with ACE (N = 68) underwent structural magnetic resonance imaging and a structured interview exploring the severity of ACE from age 3 up to 17 using the "Maltreatment and Abuse Chronology of Exposure" (MACE). Random forest regression with conditional interference trees was applied to assess the impact of ACE severity as well as the severity of ACE type, (i.e. to what extent individuals were exposed to neglect and/or abuse) at certain ages on pre-defined regions of interest such as the amygdala, hippocampus, and anterior cingulate (ACC) volume. Analyses revealed differential type and timing-specific effects of ACE on stress sensitive brain structures: Amygdala and hippocampal volume were affected by ACE severity during a period covering preadolescence and early adolescence. Crucially, this effect was driven by the severity of neglect.

Addiction Research Consortium: Losing and regaining control over drug intake (ReCoDe)-From trajectories to mechanisms and interventions.

One of the major risk factors for global death and disability is alcohol, tobacco, and illicit drug use. While there is increasing knowledge with respect to individual factors promoting the initiation and maintenance of substance use disorders (SUDs), disease trajectories involved in losing and regaining control over drug intake (ReCoDe) are still not well described. Our newly formed German Collaborative Research Centre (CRC) on ReCoDe has an interdisciplinary approach funded by the German Research Foundation (DFG) with a 12-year perspective. The main goals of our research consortium are (i) to identify triggers and modifying factors that longitudinally modulate the trajectories of losing and regaining control over drug consumption in real life, (ii) to study underlying behavioral, cognitive, and neurobiological mechanisms, and (iii) to implicate mechanism-based interventions. These goals will be achieved by: (i) using mobile health (m-health) tools to longitudinally monitor the effects of triggers (drug cues, stressors, and priming doses) and modify factors (eg, age, gender, physical activity, and cognitive control) on drug consumption patterns in real-life conditions and in animal models of addiction; (ii) the identification and computational modeling of key mechanisms mediating the effects of such triggers and modifying factors on goal-directed, habitual, and compulsive aspects of behavior from human studies and animal models; and (iii) developing and testing interventions that specifically target the underlying mechanisms for regaining control over drug intake.

Identifying nonlinear dynamical systems via generative recurrent neural networks with applications to fMRI.

A major tenet in theoretical neuroscience is that cognitive and behavioral processes are ultimately implemented in terms of the neural system dynamics. Accordingly, a major aim for the analysis of neurophysiological measurements should lie in the identification of the computational dynamics underlying task processing. Here we advance a state space model (SSM) based on generative piecewise-linear recurrent neural networks (PLRNN) to assess dynamics from neuroimaging data. In contrast to many other nonlinear time series models which have been proposed for reconstructing latent dynamics, our model is easily interpretable in neural terms, amenable to systematic dynamical systems analysis of the resulting set of equations, and can straightforwardly be transformed into an equivalent continuous-time dynamical system. The major contributions of this paper are the introduction of a new observation model suitable for functional magnetic resonance imaging (fMRI) coupled to the latent PLRNN, an efficient stepwise training procedure that forces the latent model to capture the 'true' underlying dynamics rather than just fitting (or predicting) the observations, and of an empirical measure based on the Kullback-Leibler divergence to evaluate from empirical time series how well this goal of approximating the underlying dynamics has been achieved. We validate and illustrate the power of our approach on simulated 'ground-truth' dynamical systems as well as on experimental fMRI time series, and demonstrate that the learnt dynamics harbors task-related nonlinear structure that a linear dynamical model fails to capture. Given that fMRI is one of the most common techniques for measuring brain activity non-invasively in human subjects, this approach may provide a novel step toward analyzing aberrant (nonlinear) dynamics for clinical assessment or neuroscientific research.

Deep neural networks in psychiatry.

Machine and deep learning methods, today's core of artificial intelligence, have been applied with increasing success and impact in many commercial and research settings. They are powerful tools for large scale data analysis, prediction and classification, especially in very data-rich environments ("big data"), and have started to find their way into medical applications. Here we will first give an overview of machine learning methods, with a focus on deep and recurrent neural networks, their relation to statistics, and the core principles behind them. We will then discuss and review directions along which (deep) neural networks can be, or already have been, applied in the context of psychiatry, and will try to delineate their future potential in this area. We will also comment on an emerging area that so far has been much less well explored: by embedding semantically interpretable computational models of brain dynamics or behavior into a statistical machine learning context, insights into dysfunction beyond mere prediction and classification may be gained. Especially this marriage of computational models with statistical inference may offer insights into neural and behavioral mechanisms that could open completely novel avenues for psychiatric treatment.

Back to the Basics: Resting State Functional Connectivity of the Reticular Activation System in PTSD and its Dissociative Subtype.

BACKGROUND: Brainstem and midbrain neuronal circuits that control innate, reflexive responses and arousal are increasingly recognized as central to the neurobiological framework of post-traumatic stress disorder (PTSD). The reticular activation system represents a fundamental neuronal circuit that plays a critical role not only in generating arousal but also in coordinating innate, reflexive responding. Accordingly, the present investigation aims to characterize the resting state functional connectivity of the reticular activation system in PTSD and its dissociative subtype. METHODS: We investigated patterns of resting state functional connectivity of a central node of the reticular activation system, namely, the pedunculopontine nuclei, among individuals with PTSD (n = 77), its dissociative subtype (PTSD+DS; n = 48), and healthy controls (n = 51). RESULTS: Participants with PTSD and PTSD+DS were characterized by within-group pedunculopontine nuclei resting state functional connectivity to brain regions involved in innate threat processing and arousal modulation (i.e., midbrain, amygdala, ventromedial prefrontal cortex). Critically, this pattern was most pronounced in individuals with PTSD+DS, as compared to both control and PTSD groups. As compared to participants with PTSD and controls, individuals with PTSD+DS showed enhanced pedunculopontine nuclei resting state functional connectivity to the amygdala and the parahippocampal gyrus as well as to the anterior cingulate and the ventromedial prefrontal cortex. No group differences emerged between PTSD and control groups. In individuals with PTSD+DS, state derealization/depersonalization was associated with reduced resting state functional connectivity between the left pedunculopontine nuclei and the anterior nucleus of the thalamus. Altered connectivity in these regions may restrict the thalamo-cortical transmission necessary to integrate internal and external signals at a cortical level and underlie, in part, experiences of depersonalization and derealization. CONCLUSIONS: The present findings extend the current neurobiological model of PTSD and provide emerging evidence for the need to incorporate brainstem structures, including the reticular activation system, into current conceptualizations of PTSD and its dissociative subtype.

Recurrent Neural Networks in Mobile Sampling and Intervention.

The rapid rise and now widespread distribution of handheld and wearable devices, such as smartphones, fitness trackers, or smartwatches, has opened a new universe of possibilities for monitoring emotion and cognition in everyday-life context, and for applying experience- and context-specific interventions in psychosis. These devices are equipped with multiple sensors, recording channels, and app-based opportunities for assessment using experience sampling methodology (ESM), which enables to collect vast amounts of temporally highly resolved and ecologically valid personal data from various domains in daily life. In psychosis, this allows to elucidate intermediate and clinical phenotypes, psychological processes and mechanisms, and their interplay with socioenvironmental factors, as well as to evaluate the effects of treatments for psychosis on important clinical and social outcomes. Although these data offer immense opportunities, they also pose tremendous challenges for data analysis. These challenges include the sheer amount of time series data generated and the many different data modalities and their specific properties and sampling rates. After a brief review of studies and approaches to ESM and ecological momentary interventions in psychosis, we will discuss recurrent neural networks (RNNs) as a powerful statistical machine learning approach for time series analysis and prediction in this context. RNNs can be trained on multiple data modalities simultaneously to learn a dynamical model that could be used to forecast individual trajectories and schedule online feedback and intervention accordingly. Future research using this approach is likely going to offer new avenues to further our understanding and treatments of psychosis.

Difficulties with being socially accepted: An experimental study in borderline personality disorder.

Anxious preoccupation with real or imagined abandonment is a key feature of borderline personality disorder (BPD). Recent experimental research suggests that patients with BPD do not simply show emotional overreactivity to rejection. Instead, they experience reduced connectedness with others in situations of social inclusion. Resulting consequences of these features on social behavior are not investigated yet. The aim of the present study was to investigate the differential impact of social acceptance and rejection on social expectations and subsequent social behavior in BPD. To this end, we developed the Mannheim Virtual Group Interaction Paradigm in which participants interacted with a group of computer-controlled avatars. They were led to believe that these represented real human coplayers. During these interactions, participants introduced themselves, evaluated their coplayers, assessed their social expectations and received feedback signaling either acceptance or rejection by the alleged other participants. Subsequently, participants played a modified trust game, which measured cooperative and aggressive behavior. Fifty-six nonmedicated BPD patients and 56 healthy control participants were randomly and double-blindly assigned to either the group-acceptance or group-rejection condition. BPD patients showed lower initial expectations of being socially accepted than healthy controls. After repeated presentation of social feedback, they adjusted their expectations in response to negative, but not to positive feedback. After the experience of social acceptance, BPD patients behaved less cooperatively. These experimental findings point to a clinically relevant issue in BPD: Altered cognitive and behavioral responses to social acceptance may hamper the forming of stable cooperative relationships and negatively affect future interpersonal relationships. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Generalisation of fear in PTSD related to prolonged childhood maltreatment: an experimental study.

BACKGROUND: Fear responses are particularly intense and persistent in post-traumatic stress disorder (PTSD), and can be evoked by unspecific cues that resemble the original traumatic event. Overgeneralisation of fear might be one of the underlying mechanisms. We investigated the generalisation and discrimination of fear in individuals with and without PTSD related to prolonged childhood maltreatment. METHODS: Sixty trauma-exposed women with (N = 30) and without (N = 30) PTSD and 30 healthy control participants (HC) underwent a fear conditioning and generalisation paradigm. In a contingency learning procedure, one of two circles of different sizes was associated with an electrical shock (danger cue), while the other circle represented a safety cue. During generalisation testing, online risk ratings, reaction times and fear-potentiated startle were measured in response to safety and danger cues as well as to eight generalisation stimuli, i.e. circles of parametrically varying size creating a continuum of similarity between the danger and safety cue. RESULTS: The increase in reaction times from the safety cue across the different generalisation classes to the danger cue was less pronounced in PTSD compared with HC. Moreover, PTSD participants expected higher risk of an aversive event independent of stimulus types and task. CONCLUSIONS: Alterations in generalisation constitute one part of fear memory alterations in PTSD. Neither the accuracy of a risk judgement nor the strength of the induced fear was affected. Instead, processing times as an index of uncertainty during risk judgements suggested a reduced differentiation between safety and threat in PTSD.