Burst versus continuous delivery design in digital mental health interventions: Evidence from a randomized clinical trial.

Objective: Digital mental health interventions delivered via smartphone-based apps effectively treat various conditions; however, optimizing their efficacy while minimizing participant burden remains a key challenge. In this study, we investigated the potential benefits of a burst delivery design (i.e. interventions delivered only in pre-defined time intervals) in comparison to the continuous delivery of interventions. Methods: We randomly assigned 93 participants to the continuous delivery (CD) or burst delivery (BD) group. The CD group engaged in ReApp, a mobile app that increases positive cognitive reappraisal with a consistent delivery schedule that provides five prompts per day throughout the 3-week-long study, while the BD group received five daily prompts only in the first and third weeks of the study. Results: No significant differences were found between the groups in terms of adherence, mental health outcomes (specifically depressive and anxiety symptoms), level of perceived stress, and perceived helpfulness of intervention. The BD group showed a significantly decreased perceived difficulty of intervention over time. Conclusions: The results suggest that the burst delivery may be as suitable for digital mental health interventions as the continuous delivery. The perceived difficulty of the intervention declined more steeply for the BD group, indicating that it improved the feasibility of the positive cognitive reappraisal intervention without hurting its efficacy. This outcome may inform the design of less burdensome interventions with improved outcomes in future research.

Imager-A mobile health mental imagery-based ecological momentary intervention targeting reward sensitivity: A randomized controlled trial.

Robust reward sensitivity may help preserve mental well-being in the face of adversity and has been proposed as a key stress resilience factor. Here, we present a mobile health application, "Imager," which targets reward sensitivity by training individuals to create mental images of future rewarding experiences. We conducted a two-arm randomized controlled trial with 95 participants screened for reward sensitivity. Participants in the intervention group received an ecological momentary intervention-Imager, which encouraged participants to create mental images of rewarding events for 1 week. The control group participants received only ecological momentary assessment, without the instruction to generate mental images. Adherence to Imager was high; participants in the intervention group engaged in 88% of the planned activities. In the follow-up assessment, the intervention group reported less mental health symptoms, mainly in depression (ß = -0.34, df = 93, p = .004) and less perceived stress (ß = -0.18, df = 93, p = .035), than control group participants and compared with the baseline assessment. Our results show the positive effects of Imager on mental health symptoms. The encouraging effects of the app on mental health outcomes may lead to greater use of ecological momentary interventions in the clinical preventive practice of affective disorders.

Psychological Resilience Factors and Their Association With Weekly Stressor Reactivity During the COVID-19 Outbreak in Europe: Prospective Longitudinal Study.

BACKGROUND: Cross-sectional relationships between psychosocial resilience factors (RFs) and resilience, operationalized as the outcome of low mental health reactivity to stressor exposure (low "stressor reactivity" [SR]), were reported during the first wave of the COVID-19 pandemic in 2020. OBJECTIVE: Extending these findings, we here examined prospective relationships and weekly dynamics between the same RFs and SR in a longitudinal sample during the aftermath of the first wave in several European countries. METHODS: Over 5 weeks of app-based assessments, participants reported weekly stressor exposure, mental health problems, RFs, and demographic data in 1 of 6 different languages. As (partly) preregistered, hypotheses were tested cross-sectionally at baseline (N=558), and longitudinally (n=200), using mixed effects models and mediation analyses. RESULTS: RFs at baseline, including positive appraisal style (PAS), optimism (OPT), general self-efficacy (GSE), perceived good stress recovery (REC), and perceived social support (PSS), were negatively associated with SR scores, not only cross-sectionally (baseline SR scores; all P<.001) but also prospectively (average SR scores across subsequent weeks; positive appraisal (PA), P=.008; OPT, P<.001; GSE, P=.01; REC, P<.001; and PSS, P=.002). In both associations, PAS mediated the effects of PSS on SR (cross-sectionally: 95% CI -0.064 to -0.013; prospectively: 95% CI -0.074 to -0.0008). In the analyses of weekly RF-SR dynamics, the RFs PA of stressors generally and specifically related to the COVID-19 pandemic, and GSE were negatively associated with SR in a contemporaneous fashion (PA, P<.001; PAC,P=.03; and GSE, P<.001), but not in a lagged fashion (PA, P=.36; PAC, P=.52; and GSE, P=.06). CONCLUSIONS: We identified psychological RFs that prospectively predict resilience and cofluctuate with weekly SR within individuals. These prospective results endorse that the previously reported RF-SR associations do not exclusively reflect mood congruency or other temporal bias effects. We further confirm the important role of PA in resilience.

Dynamic Modelling of Mental Resilience in Young Adults: Protocol for a Longitudinal Observational Study (DynaM-OBS).

BACKGROUND: Stress-related mental disorders are highly prevalent and pose a substantial burden on individuals and society. Improving strategies for the prevention and treatment of mental disorders requires a better understanding of their risk and resilience factors. This multicenter study aims to contribute to this endeavor by investigating psychological resilience in healthy but susceptible young adults over 9 months. Resilience is conceptualized in this study as the maintenance of mental health or quick recovery from mental health perturbations upon exposure to stressors, assessed longitudinally via frequent monitoring of stressors and mental health. OBJECTIVE: This study aims to investigate the factors predicting mental resilience and adaptive processes and mechanisms contributing to mental resilience and to provide a methodological and evidence-based framework for later intervention studies. METHODS: In a multicenter setting, across 5 research sites, a sample with a total target size of 250 young male and female adults was assessed longitudinally over 9 months. Participants were included if they reported at least 3 past stressful life events and an elevated level of (internalizing) mental health problems but were not presently affected by any mental disorder other than mild depression. At baseline, sociodemographic, psychological, neuropsychological, structural, and functional brain imaging; salivary cortisol and α-amylase levels; and cardiovascular data were acquired. In a 6-month longitudinal phase 1, stressor exposure, mental health problems, and perceived positive appraisal were monitored biweekly in a web-based environment, while ecological momentary assessments and ecological physiological assessments took place once per month for 1 week, using mobile phones and wristbands. In a subsequent 3-month longitudinal phase 2, web-based monitoring was reduced to once a month, and psychological resilience and risk factors were assessed again at the end of the 9-month period. In addition, samples for genetic, epigenetic, and microbiome analyses were collected at baseline and at months 3 and 6. As an approximation of resilience, an individual stressor reactivity score will be calculated. Using regularized regression methods, network modeling, ordinary differential equations, landmarking methods, and neural net-based methods for imputation and dimension reduction, we will identify the predictors and mechanisms of stressor reactivity and thus be able to identify resilience factors and mechanisms that facilitate adaptation to stressors. RESULTS: Participant inclusion began in October 2020, and data acquisition was completed in June 2022. A total of 249 participants were assessed at baseline, 209 finished longitudinal phase 1, and 153 finished longitudinal phase 2. CONCLUSIONS: The Dynamic Modelling of Resilience-Observational Study provides a methodological framework and data set to identify predictors and mechanisms of mental resilience, which are intended to serve as an empirical foundation for future intervention studies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39817.

Traumatic stress load and stressor reactivity score associated with accelerated gray matter maturation in youths indexed by normative models.

Understanding how traumatic stress affects typical brain development during adolescence is critical to elucidate underlying mechanisms related to both maladaptive functioning and resilience after traumatic exposures. The current study aimed to map deviations from normative ranges of brain gray matter for youths with traumatic exposures. For each cortical and subcortical gray matter region, normative percentiles of variations were established using structural MRI from typically developing youths without any traumatic exposure (n = 245; age range = 8-23) from the Philadelphia Neurodevelopmental Cohort (PNC). The remaining PNC participants with neuroimaging data (n = 1129) were classified as either within the normative range (5-95%), delayed (>95%) or accelerated (<5%) maturational ranges for each region using the normative model. An averaged quantile regression index was calculated across all regions. Mediation models revealed that high traumatic stress load was positively associated with poorer cognitive functioning and greater psychopathology, and these associations were mediated by accelerated gray matter maturation. Furthermore, higher stressor reactivity scores, which represent a less resilient response under traumatic stress, were positively correlated with greater acceleration of gray matter maturation (r = 0.224, 95% CI = [0.17, 0.28], p < 0.001), suggesting that more accelerated maturation was linked to greater stressor response regardless of traumatic stress load. We conclude that traumatic stress is a source of deviation from normative brain development associated with poorer cognitive functioning and more psychopathology in the long run.

Gyrification in relation to cortical thickness in the congenitally blind.

Greater cortical gyrification (GY) is linked with enhanced cognitive abilities and is also negatively related to cortical thickness (CT). Individuals who are congenitally blind (CB) exhibits remarkable functional brain plasticity which enables them to perform certain non-visual and cognitive tasks with supranormal abilities. For instance, extensive training using touch and audition enables CB people to develop impressive skills and there is evidence linking these skills to cross-modal activations of primary visual areas. There is a cascade of anatomical, morphometric and functional-connectivity changes in non-visual structures, volumetric reductions in several components of the visual system, and CT is also increased in CB. No study to date has explored GY changes in this population, and no study has explored how variations in CT are related to GY changes in CB. T1-weighted 3D structural magnetic resonance imaging scans were acquired to examine the effects of congenital visual deprivation in cortical structures in a healthy sample of 11 CB individuals (6 male) and 16 age-matched sighted controls (SC) (10 male). In this report, we show for the first time an increase in GY in several brain areas of CB individuals compared to SC, and a negative relationship between GY and CT in the CB brain in several different cortical areas. We discuss the implications of our findings and the contributions of developmental factors and synaptogenesis to the relationship between CT and GY in CB individuals compared to SC. F.

Choices of (in)action in obesity: Implications for research on treatment and prevention.

The obesity epidemic has crossed social-demographic barriers and is a matter of significant concern. Why do individuals fail to restrain from eating high-calorie foods and fail to follow treatment routines that reduce the risk of health complications? These questions have been addressed through behavioral and brain imaging studies on prefrontal cortex inhibitory mechanisms. Failure to inhibit undesirable behaviors has become a hallmark of obesity. In many life situations, obesity risk is increased by inaction (e.g., not taking blood pressure medication, not following a healthy diet). Risk by inaction has been defined as passive risk-taking, and it is correlated with traits such as procrastination, future time perspective, and cognitive avoidance. To the present, passive tendencies, specifically in the context of risk-taking behaviors, have not been addressed in the obesity literature. We introduce a framework in which active and passive risk-taking behaviors are integrated within the scope of bidirectional models of obesity that describe the brain as both the cause and the consequence of obesity vulnerability. The present perspective aims to foster new research on treatment and prevention, and also on the neurobiology of passive behaviors in obesity and other metabolic conditions.

Obliviate! Reviewing Neural Fundamentals of Intentional Forgetting from a Meta-Analytic Perspective.

Intentional forgetting (IF) is an important adaptive mechanism necessary for correct memory functioning, optimal psychological wellbeing, and appropriate daily performance. Due to its complexity, the neuropsychological processes that give birth to successful intentional forgetting are not yet clearly known. In this study, we used two different meta-analytic algorithms, Activation Likelihood Estimation (ALE) & Latent Dirichlet Allocation (LDA) to quantitatively assess the neural correlates of IF and to evaluate the degree of compatibility between the proposed neurobiological models and the existing brain imaging data. We found that IF involves the interaction of two networks, the main "core regions" consisting of a primarily right-lateralized frontal-parietal circuit that is activated irrespective of the paradigm used and sample characteristics and a second less constrained "supportive network" that involves frontal-hippocampal interactions when IF takes place. Additionally, our results support the validity of the inhibitory or thought suppression hypothesis. The presence of a neural signature of IF that is stable regardless of experimental paradigms is a promising finding that may open new venues for the development of effective clinical interventions.

A systematic examination of the neural correlates of subjective time perception with fMRI and tDCS.

The ability to keep track of time is one of the fundamental human behaviours that enhance survival in the wild. It is still an essential skill that enables an individual to function well in modern society. In the present study, we tested the attentional gate model, one of the most common conceptual frameworks in studies of subjective time perception. Its utility has been well established, but it has been criticised for its lack of neurophysiological support; few studies attempted to systematically identify its components and their neural correlates. Previous studies established that the dorsolateral prefrontal cortex (DLPFC) was associated with working memory tasks and a correlation between activity in the cerebellum and the timing of tasks. An fMRI study was conducted to confirm that these two cortical regions were activated during the execution of a new time discrimination task that considers individual variations in subjective time perception. Simulations were conducted to optimize the electrode placement in order to maximize the electric fields of tDCS perturbation to these two areas. According to the attentional gate model, hypotheses about tDCS perturbation to subjective time perception, attention and working memory were formulated and tested. Attention and working memory were measured by the attention network and N-back tasks. There are weak effects to the perceived subjective equivalent and the reaction time in the attention network task, but both are not statistically significant after correction for multiple comparisons. Exploration analyses show a link between attention and subjective time perception after tDCS perturbation. To conclude, the results do not support the attentional gate model, but show a linkage between attention and subjective time perception in terms of similar neural circuits and their relationships under certain circumstances.

Individualizing deep dynamic models for psychological resilience data.

Deep learning approaches can uncover complex patterns in data. In particular, variational autoencoders achieve this by a non-linear mapping of data into a low-dimensional latent space. Motivated by an application to psychological resilience in the Mainz Resilience Project, which features intermittent longitudinal measurements of stressors and mental health, we propose an approach for individualized, dynamic modeling in this latent space. Specifically, we utilize ordinary differential equations (ODEs) and develop a novel technique for obtaining person-specific ODE parameters even in settings with a rather small number of individuals and observations, incomplete data, and a differing number of observations per individual. This technique allows us to subsequently investigate individual reactions to stimuli, such as the mental health impact of stressors. A potentially large number of baseline characteristics can then be linked to this individual response by regularized regression, e.g., for identifying resilience factors. Thus, our new method provides a way of connecting different kinds of complex longitudinal and baseline measures via individualized, dynamic models. The promising results obtained in the exemplary resilience application indicate that our proposal for dynamic deep learning might also be more generally useful for other application domains.

Cognitive and brain correlates of acquired number-colour synaesthetic-like associations.

Synaesthesia is a condition in which one sensory dimension triggers another sensation. The exact contribution of genetic and environmental factors in synaesthesia is not yet fully understood. Most synaesthesia phenotypes involve associations in which the synaesthetic inducer constitutes some form of linguistic/conceptual information acquired during the course of development (e.g., digits, letters, and names of months). To study the role of learning in synaesthesia, we induced synaesthesia by training and examined the behavioural and brain correlates of number-colour associations. We took advantage of the well-known behavioural and neural signature of numbers and used number symbols as inducers. Short (2 weeks) and long (4 weeks) training protocols were conducted with two different groups. Task-related BOLD response was acquired while participants performed Stroop tasks requiring naming colours while ignoring the stimuli (i.e., number symbols, dots, words). If the arbitrary association involving number-colour is automatic, the irrelevant dimension (i.e., numbers) would interfere with the colour response. In addition, if number-colour associations are transferred to linguistic and non-symbolic representations, the passive viewing of stimuli (i.e., words and dots) would disrupt colour naming. Behavioural findings showed automatic associations as both training protocols elicited reliable congruency effects for all stimulus dimensions. Congruency effects following both training protocols produced reliable brain activations in various cortical sites involved in number and in cognitive control. The behavioural and brain patterns reported here support the role of learning in the brain correlates of developmental synaesthesia and provide the first evidence that automatic associations involving different magnitude dimensions can be acquired.

Snapshot of a social movement: Mental health and protest classes in Hong Kong.

BACKGROUND: Popular protests have broken out worldwide, particularly in the last few years. In 2019, numerous demonstrations against an extradition bill occurred in Hong Kong until pandemic restrictions were imposed. The policing response relied heavily on methods such as batons, tear gas and rubber bullets. Given the relevance for other geographical contexts, the current study investigated the mental health impacts on protest participants and spillover to community members. METHODS: Surveys were disseminated on social media in August and October 2019 to collect demographics, political views, protest participation, exposure to (protest-related) potentially traumatic events (PTEs) and mental health symptoms. A latent class analysis (LCA) was conducted using demographic data and inter-class differences in PTEs and mental health symptoms were examined. RESULTS: There were 37,541 (59.8% female) and 40,703 (50.0% female) responses in August and October. Respondents, even those with low participation, reported significant levels of depression, anxiety, and symptoms of traumatic stress (STS). The LCA suggested a 5-class solution (youth, allies, supporters, sympathizers, and frontliners). Mental health symptoms and PTEs varied with class membership, with 50.8% of frontliners reporting severe STS. LIMITATIONS: The non-random sampling and self-reported measures may over-estimate the prevalence of mental distress in the wider population. CONCLUSIONS: Large numbers of pro-democracy supporters in Hong Kong reported high rates of depression, anxiety and STS during mass protests. Younger and more heavily involved respondents faced the highest mental health risks, however elevated rates were also observed for respondents with low participation.

The Frequent Stressor and Mental Health Monitoring-Paradigm: A Proposal for the Operationalization and Measurement of Resilience and the Identification of Resilience Processes in Longitudinal Observational Studies.

Resilience has been defined as the maintenance or quick recovery of mental health during and after times of adversity. How to operationalize resilience and to determine the factors and processes that lead to good long-term mental health outcomes in stressor-exposed individuals is a matter of ongoing debate and of critical importance for the advancement of the field. One of the biggest challenges for implementing an outcome-based definition of resilience in longitudinal observational study designs lies in the fact that real-life adversity is usually unpredictable and that its substantial qualitative as well as temporal variability between subjects often precludes defining circumscribed time windows of inter-individually comparable stressor exposure relative to which the maintenance or recovery of mental health can be determined. To address this pertinent issue, we propose to frequently and regularly monitor stressor exposure (E) and mental health problems (P) throughout a study's observation period [Frequent Stressor and Mental Health Monitoring (FRESHMO)-paradigm]. On this basis, a subject's deviation at any single monitoring time point from the study sample's normative E-P relationship (the regression residual) can be used to calculate that subject's current mental health reactivity to stressor exposure ("stressor reactivity," SR). The SR score takes into account the individual extent of experienced adversity and is comparable between and within subjects. Individual SR time courses across monitoring time points reflect intra-individual temporal variability in SR, where periods of under-reactivity (negative SR score) are associated with accumulation of fewer mental health problems than is normal for the sample. If FRESHMO is accompanied by regular measurement of potential resilience factors, temporal changes in resilience factors can be used to predict SR time courses. An increase in a resilience factor measurement explaining a lagged decrease in SR can then be considered to index a process of adaptation to stressor exposure that promotes a resilient outcome (an allostatic resilience process). This design principle allows resilience research to move beyond merely determining baseline predictors of resilience outcomes, which cannot inform about how individuals successfully adjust and adapt when confronted with adversity. Hence, FRESHMO plus regular resilience factor monitoring incorporates a dynamic-systems perspective into resilience research.

Psychomorbidity, Resilience, and Exacerbating and Protective Factors During the SARS-CoV-2 Pandemic.

BACKGROUND: The SARS-CoV-2 pandemic has caused mental stress in a number of ways: overstrain of the health care system, lockdown of the economy, restricted opportunities for interpersonal contact and excursions outside the home and workplace, and quarantine measures where necessary. In this article, we provide an overview of psychological distress in the current pandemic, identifying protective factors and risk factors. METHODS: The PubMed, PsycINFO, and Web of Science databases were systematically searched for relevant publications (1 January 2019 - 16 April 2020). This study was registered in OSF Registries (osf.io/34j8g). Data on mental stress and resilience in Germany were obtained from three surveys carried out on more than 1000 participants each in the framework of the COSMO study (24 March, 31 March, and 21 April 2020). RESULTS: 18 studies from China and India, with a total of 79 664 participants, revealed increased stress in the general population, with manifestations of depression and anxiety, post-traumatic stress, and sleep disturbances. Stress was more marked among persons working in the health care sector. Risk factors for stress included patient contact, female sex, impaired health status, worry about family members and significant others, and poor sleep quality. Protective factors included being informed about the increasing number of persons who have recovered from COVID, social support, and a lower perceived infectious risk. The COSMO study, though based on an insufficiently representative population sample because of a low questionnaire return rate (<20%), revealed increased rates of despondency, loneliness, and hopelessness in the German population as compared to norm data, with no change in estimated resilience. CONCLUSION: Stress factors associated with the current pandemic probably increase stress by causing anxiety and depression. Once the protective factors and risk factors have been identified, these can be used to develop psychosocial interventions. The informativeness of the results reported here is limited by the wide variety of instruments used to acquire data and by the insufficiently representative nature of the population samples.

Replication of fMRI group activations in the neuroimaging battery for the Mainz Resilience Project (MARP).

Motivated by the recent replicability crisis we tested replicability of functional magnetic resonance imaging (fMRI) group activations in two independent samples. An identical behavioral and fMRI test battery for the longitudinal investigation of stress resilience mechanisms was developed for the Mainz Resilience Project (MARP) and conducted in a discovery (N = 54) and a replication sample (N = 103). The test battery consisted of a stress reactivity task, a reward sensitivity task, a fear conditioning and extinction paradigm, two volitional reappraisal tasks and an emotional interference inhibition task. Replicability of group activations was tested with the Jaccard index and the Intra Class Correlation (ICC). Overall, we observed good to excellent replicability of activations at the whole brain level. Only a minority of contrasts showed unsatisfactory replicability. Replicability at the level of individual regions of interest (ROIs) was generally lower. Tasks with stronger activation in the discovery sample showed better replicability.

Space counts! Brain correlates of spatial and numerical representations in synaesthesia.

Over-learned semantic representations, such as numbers, are strongly associated with space in normal cognition, and in the phenomenon called number-space synaesthesia. In number-space synaesthesia, numbers are linked to spatial locations in an idiosyncratic way. Synaesthetes report numbers as belonging to a specific location, or feelings that a specific location is the right location for that number. What does really differentiate synaesthetes from non-synaesthetes with respect to their number-space representation? Here we present a number-space synaesthete, MkM, whose number-space representation dramatically differs from that of controls. We examined the impact of spatial distance with respect to MkM's mental number line (MNL), and numerical distance with respect to the conceptualized horizontal representation of numbers. In a behavioural experiment, MkM and controls performed number comparison tasks in which they reported either the larger numerical value (number task) or the larger stimulus (physical task) (Experiment 1). A spatial distance effect was found only for MkM. In a brain imaging experiment, MkM and controls compared a single presented digit with an internal reference (Experiment 2). Consistent with the behavioural results, spatial distance elicited significant brain activations only for MkM in different cortical sites including the left supramarginal gyrus. Numerical distance elicited significant brain activations only for controls in the left somatosensory cortex and in the right operculum. We propose that two types of representation are accessed in synaesthesia: one derived by the semantic coding of numbers across space (described by the MNL), and an explicit spatial representation derived from the position of number within the synaesthetic association. The level of overlap between these two forms of representation depends on the shape of the synaesthetic number-space association.

Increased Neural Activity in Mesostriatal Regions after Prefrontal Transcranial Direct Current Stimulation and l-DOPA Administration.

Dopamine dysfunction is associated with a wide range of neuropsychiatric disorders commonly treated pharmacologically or invasively. Recent studies provide evidence for a nonpharmacological and noninvasive alternative that allows similar manipulation of the dopaminergic system: transcranial direct current stimulation (tDCS). In rodents, tDCS has been shown to increase neural activity in subcortical parts of the dopaminergic system, and recent studies in humans provide evidence that tDCS over prefrontal regions induces striatal dopamine release and affects reward-related behavior. Based on these findings, we used fMRI in healthy human participants and measured the fractional amplitude of low-frequency fluctuations to assess spontaneous neural activity strength in regions of the mesostriatal dopamine system before and after tDCS over prefrontal regions (n = 40, 22 females). In a second study, we examined the effect of a single dose of the dopamine precursor levodopa (l-DOPA) on mesostriatal fractional amplitude of low-frequency fluctuation values in male humans (n = 22) and compared the results between both studies. We found that prefrontal tDCS and l-DOPA both enhance neural activity in core regions of the dopaminergic system and show similar subcortical activation patterns. We furthermore assessed the spatial similarity of whole-brain statistical parametric maps, indicating tDCS- and l-DOPA-induced activation, and >100 neuronal receptor gene expression maps based on transcriptional data from the Allen Institute for Brain Science. In line with a specific activation of the dopaminergic system, we found that both interventions predominantly activated regions with high expression levels of the dopamine receptors D2 and D3.SIGNIFICANCE STATEMENT Studies in animals and humans provide evidence that transcranial direct current stimulation (tDCS) allows a manipulation of the dopaminergic system. Based on these findings, we used fMRI to assess changes in spontaneous neural activity strength in the human dopaminergic system after prefrontal tDCS compared with the administration of the dopamine precursor and standard anti-Parkinson drug levodopa (l-DOPA). We found that prefrontal tDCS and l-DOPA both enhance neural activity in core regions of the dopaminergic system and show similar subcortical activation patterns. Using whole-brain transcriptional data of >100 neuronal receptor genes, we found that both interventions specifically activated regions with high expression levels of the dopamine receptors D2 and D3.

Cognitive variability in bipolar I disorder: A cluster-analytic approach informed by resting-state data.

BACKGROUND: While the presence of cognitive performance deficits in bipolar disorder I (BD-I) is well established, there is no consensus about which cognitive abilities are affected. Heterogeneous phenotypes displayed in BD-I further suggest the existence of subgroups among the disorder. The present study sought to identify different cognitive profiles among BD-I patients as well as potentially underlying neuronal network changes. METHODS: 54 euthymic BD-I patients underwent cognitive testing and resting state neuroimaging. Hierarchical cluster-analysis was performed on executive function scores of bipolar patients. The derived clusters were compared against 54 age-, gender- and IQ-matched healthy controls (HC) to facilitate the interpretation of results. Further, resting state network properties were compared to identify differences probably underlying cognitive profiles. RESULTS: A three-cluster solution emerged. Cluster 1 (n = 22) was characterized by deficits in cognitive flexibility and motor inhibition, cluster 2 (n = 12) displayed impulsive decision-making, while cluster 3 (n = 20) showed good visuospatial planning. Weaker connections in cluster 1 compared to cluster 2 were found between regions activated during tasks cluster 1 showed deficits on. Cluster 3 had a higher modularity than cluster 2, which correlated positively with problem solving performance and risk-taking in this cluster. CONCLUSION: Obtained clusters showed distinct cognitive profiles, characterized by deficits and strengths, most of which remained precluded in a general comparison. Weaker interregional connections and separated subnetworks might underly behavioral deficits and strengths, respectively. The findings help explain the phenotypic heterogeneity observed in BD-I. This article is part of the Special Issue entitled 'Current status of the neurobiology of aggression and impulsivity'.

The Functional Role of Large-scale Brain Network Coordination in Placebo-induced Anxiolysis.

Anxiety reduction through mere expectation of anxiolytic treatment effects (placebo anxiolysis) has enormous clinical importance. Recent behavioral and electrophysiological data suggest that placebo anxiolysis involves reduced vigilance and enhanced internalization of attention; however, the underlying neurobiological mechanisms are not yet clear. Given the fundamental function of intrinsic connectivity networks (ICNs) in basic cognitive processes, we investigated ICN activity patterns associated with externally and internally directed mental states under the influence of an anxiolytic placebo medication. Based on recent findings, we specifically analyzed the functional role of the rostral anterior cingulate cortex (rACC) in coordinating placebo-dependent cue-related (phasic) and cue-unrelated (sustained) network activity. Under placebo, we observed a down-regulation of the entire salience network (SN), particularly in response to threatening cues. The rACC exhibited enhanced cue-unrelated functional connectivity (FC) with the SN, which correlated with reductions in tonic arousal and anxiety. Hence, apart from the frequently reported modulation of aversive cue responses, the rACC appears to be crucially involved in exerting a tonically dampening control over salience-responsive structures. In line with a more internally directed mental state, we also found enhanced FC within the default mode network (DMN), again predicting reductions in anxiety under placebo.