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.

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.

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.

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.

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.

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.

Pattern Analyses Reveal Separate Experience-Based Fear Memories in the Human Right Amygdala.

Learning fear via the experience of contingencies between a conditioned stimulus (CS) and an aversive unconditioned stimulus (US) is often assumed to be fundamentally different from learning fear via instructions. An open question is whether fear-related brain areas respond differently to experienced CS-US contingencies than to merely instructed CS-US contingencies. Here, we contrasted two experimental conditions where subjects were instructed to expect the same CS-US contingencies while only one condition was characterized by prior experience with the CS-US contingency. Using multivoxel pattern analysis of fMRI data, we found CS-related neural activation patterns in the right amygdala (but not in other fear-related regions) that dissociated between whether a CS-US contingency had been instructed and experienced versus merely instructed. A second experiment further corroborated this finding by showing a category-independent neural response to instructed and experienced, but not merely instructed, CS presentations in the human right amygdala. Together, these findings are in line with previous studies showing that verbal fear instructions have a strong impact on both brain and behavior. However, even in the face of fear instructions, the human right amygdala still shows a separable neural pattern response to experience-based fear contingencies.SIGNIFICANCE STATEMENT In our study, we addressed a fundamental problem of the science of human fear learning and memory, namely whether fear learning via experience in humans relies on a neural pathway that can be separated from fear learning via verbal information. Using two new procedures and recent advances in the analysis of brain imaging data, we localized purely experience-based fear processing and memory in the right amygdala, thereby making a direct link between human and animal research.

Domain General Sequence Operations Contribute to Pre-SMA Involvement in Visuo-spatial Processing.

This study used 3T MRI to elucidate the functional role of supplementary motor area (SMA) in relation to visuo-spatial processing. A localizer task contrasting sequential number subtraction and repetitive button pressing was used to functionally delineate non-motor sequence processing in pre-SMA, and activity in SMA-proper associated with motor sequencing. Patterns of BOLD responses in these regions were then contrasted to those from two tasks of visuo-spatial processing. In one task participants performed Mental Rotation (MR) in which recognition memory judgments were made to previously memorized 2D novel patterns across image-plane rotations. The other task involved abstract grid navigation (GN) in which observers computed a series of imagined location shifts in response to directional (arrow) cues around a mental grid. The results showed overlapping activation in pre-SMA for sequential subtraction and both visuo-spatial tasks. These results suggest that visuo-spatial processing is supported by non-motor sequence operations that involve pre-SMA. More broadly, these data further highlight the functional heterogeneity of pre-SMA, and show that its role extends to processes beyond the planning and online control of movement.

Changes in brain functional connectivity patterns are driven by an individual lesion in MS: a resting-state fMRI study.

Diffuse inflammation in multiple sclerosis (MS) extends beyond focal lesion sites, affecting interconnected regions; however, little is known about the impact of an individual lesion affecting major white matter (WM) pathways on brain functional connectivity (FC). Here, we longitudinally assessed the effects of acute and chronic lesions on FC in relapsing-remitting MS (RRMS) patients using resting-state fMRI. 45 MRI data sets from 9 RRMS patients were recorded using 3T MR scanner over 5 time points at 8 week intervals. Patients were divided into two groups based on the presence (n = 5; MS+) and absence (n = 4; MS-) of a lesion at a predilection site for MS. While FC levels were found not to fluctuate significantly in the overall patient group, the MS+ patient group showed increased FC in the contralateral cuneus and precuneus and in the ipsilateral precuneus (p < 0.01, corrected). This can be interpreted as the recruitment of intact cortical regions to compensate for tissue damage. During the study, one patient developed an acute WM lesion in the left posterior periventricular space. A marked increase in FC in the right pre-, post-central gyrus, right superior frontal gyrus, the left cuneus, the vermis and the posterior and anterior lobes of the cerebellum was noted following the clinical relapse, which gradually decreased in subsequent follow-ups, suggesting short-term functional reorganization during the acute phase. This strongly suggests that the lesion-related network changes observed in patients with chronic lesions occur as a result of reorganization processes following the initial appearance of an acute lesion.

The perception of time while perceiving dynamic emotional faces.

Emotion plays an essential role in the perception of time such that time is perceived to "fly" when events are enjoyable, while unenjoyable moments are perceived to "drag." Previous studies have reported a time-drag effect when participants are presented with emotional facial expressions, regardless of the emotion presented. This effect can hardly be explained by induced emotion given the heterogeneous nature of emotional expressions. We conducted two experiments (n = 44 and n = 39) to examine the cognitive mechanism underlying this effect by presenting dynamic sequences of emotional expressions to participants. Each sequence started with a particular expression, then morphed to another. The presentation of dynamic facial expressions allows a comparison between the time-drag effect of homogeneous pairs of emotional expressions sharing similar valence and arousal to heterogeneous pairs. Sequences of seven durations (400, 600, 800, 1000, 1200, 1400, 1600 ms) were presented to participants, who were asked to judge whether the sequences were closer to 400 or 1600 ms in a two-alternative forced choice task. The data were then collated according to conditions and fit into cumulative Gaussian curves to estimate the point of subjective equivalence indicating the perceived duration of 1000 ms. Consistent with previous reports, a feeling of "time dragging" is induced regardless of the sequence presented, such that 1000 ms is perceived to be longer than 1000 ms. In addition, dynamic facial expressions exert a greater effect on perceived time drag than static expressions. The effect is most prominent when the dynamics involve an angry face or a change in valence. The significance of this sensitivity is discussed in terms of emotion perception and its evolutionary significance for our attention mechanism.

Neural mechanisms of placebo anxiolysis.

The beneficial effects of placebo treatments on fear and anxiety (placebo anxiolysis) are well known from clinical practice, and there is strong evidence indicating a contribution of treatment expectations to the efficacy of anxiolytic drugs. Although clinically highly relevant, the neural mechanisms underlying placebo anxiolysis are poorly understood. In two studies in humans, we tested whether the administration of an inactive treatment along with verbal suggestions of anxiolysis can attenuate experimentally induced states of phasic fear and/or sustained anxiety. Phasic fear is the response to a well defined threat and includes attentional focusing on the source of threat and concomitant phasic increases of autonomic arousal, whereas in sustained states of anxiety potential and unclear danger requires vigilant scanning of the environment and elevated tonic arousal levels. Our placebo manipulation consistently reduced vigilance measured in terms of undifferentiated reactivity to salient cues (indexed by subjective ratings, skin conductance responses and EEG event-related potentials) and tonic arousal [indexed by cue-unrelated skin conductance levels and enhanced EEG alpha (8-12 Hz) activity], indicating a downregulation of sustained anxiety rather than phasic fear. We also observed a placebo-dependent sustained increase of frontal midline EEG theta (4-7 Hz) power and frontoposterior theta coupling, suggesting the recruitment of frontally based cognitive control functions. Our results thus support the crucial role of treatment expectations in placebo anxiolysis and provide insight into the underlying neural mechanisms.

"Opening an emotional dimension in me": changes in emotional reactivity and emotion regulation in a case of executive impairment after left fronto-parietal damage.

Dysexecutive impairment is a common problem after brain injury, particularly after damage to the lateral surface of the frontal lobes. There is a large literature describing the cognitive deficits associated with executive impairment after dorsolateral damage; however, little is known about its impact on emotional functioning. This case study describes changes in a 72-year-old man (Professor F) who became markedly dysexecutive after a left fron-to-parietal stroke. Professor F's case is remarkable in that, despite exhibiting typical executive impairments, abstraction and working memory capacities were spared. Such preservation of insight-related capacities allowed him to offer a detailed account of his emotional changes. Quantitative and qualitative tools were used to explore changes in several well-known emotional processes. The results suggest that Professor F's two main emotional changes were in the domain of emotional reactivity (increased experience of both positive and negative emotions) and emotion regulation (down-regulation of sadness). Professor F related both changes to difficulties in his thinking process, especially a difficulty generating and manipulating thoughts during moments of negative arousal. These results are discussed in relation to the literature on executive function and emotion regulation. The relevance of these findings for neuropsychological rehabilitation and for the debate on the neural basis of emotional processes is addressed.

Almost winning: induced MEG theta power in insula and orbitofrontal cortex increases during gambling near-misses and is associated with BOLD signal and gambling severity.

In slot machine gambling, the "near-miss effect" (when a losing display physically resembles an actual win display) has been implicated in pathological gambling (PG). Functional magnetic resonance imaging (fMRI) with PG and non-PG participants shows that near-misses recruit reward-related circuitry, but little is known about the temporal dynamics and oscillatory changes underlying near-misses. The present multi-modal imaging study investigated the near-miss effect by combining the spatial resolution of blood oxygen-level dependent (BOLD)-fMRI with the spatial and temporal resolution of magnetoencephalography (MEG) during a slot machine task in PG and non-PG groups. Given previous findings on outcome (win and near-miss) processing, functional overlap was hypothesized between induced changes in temporal oscillations and BOLD response to wins and near-misses in PG. We first validated our task in a sample of varying gambling severity using BOLD-fMRI and then compared PG and non-PG participants using MEG to investigate changes in induced oscillatory power associated with win and near-miss, relative to loss, outcomes. Across both modalities, near-misses recruited similar brain regions to wins, including right inferior frontal gyrus and insula. Using MEG, increased theta-band (4-7Hz) oscillations to near-misses were observed in the insula and right orbitofrontal cortex (OFC). Furthermore, this theta-band activity was positively associated with gambling severity. These findings demonstrate that the near-miss effect in insula and OFC is associated with induced theta oscillations. The significance of these findings for theories of PG and the development of potential biomarkers and therapeutic targets is discussed.