Optimizing Outcomes in Psychotherapy for Anxiety Disorders Using Smartphone-Based and Passive Sensing Features: Protocol for a Randomized Controlled Trial.

BACKGROUND: Psychotherapies, such as cognitive behavioral therapy (CBT), currently have the strongest evidence of durable symptom changes for most psychological disorders, such as anxiety disorders. Nevertheless, only about half of individuals treated with CBT benefit from it. Predictive algorithms, including digital assessments and passive sensing features, could better identify patients who would benefit from CBT, and thus, improve treatment choices. OBJECTIVE: This study aims to establish predictive features that forecast responses to transdiagnostic CBT in anxiety disorders and to investigate key mechanisms underlying treatment responses. METHODS: This study is a 2-armed randomized controlled clinical trial. We include patients with anxiety disorders who are randomized to either a transdiagnostic CBT group or a waitlist (referred to as WAIT). We index key features to predict responses prior to starting treatment using subjective self-report questionnaires, experimental tasks, biological samples, ecological momentary assessments, activity tracking, and smartphone-based passive sensing to derive a multimodal feature set for predictive modeling. Additional assessments take place weekly at mid- and posttreatment and at 6- and 12-month follow-ups to index anxiety and depression symptom severity. We aim to include 150 patients, randomized to CBT versus WAIT at a 3:1 ratio. The data set will be subject to full feature and important features selected by minimal redundancy and maximal relevance feature selection and then fed into machine leaning models, including eXtreme gradient boosting, pattern recognition network, and k-nearest neighbors to forecast treatment response. The performance of the developed models will be evaluated. In addition to predictive modeling, we will test specific mechanistic hypotheses (eg, association between self-efficacy, daily symptoms obtained using ecological momentary assessments, and treatment response) to elucidate mechanisms underlying treatment response. RESULTS: The trial is now completed. It was approved by the Cantonal Ethics Committee, Zurich. The results will be disseminated through publications in scientific peer-reviewed journals and conference presentations. CONCLUSIONS: The aim of this trial is to improve current CBT treatment by precise forecasting of treatment response and by understanding and potentially augmenting underpinning mechanisms and personalizing treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT03945617; https://clinicaltrials.gov/ct2/show/results/NCT03945617. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42547.

Dissociating the Neural Correlates of Consciousness and Task Relevance in Face Perception Using Simultaneous EEG-fMRI.

Current theories of visual consciousness disagree about whether it emerges during early stages of processing in sensory brain regions or later when a widespread frontoparietal network becomes involved. Moreover, disentangling conscious perception from task-related postperceptual processes (e.g., report) and integrating results across different neuroscientific methods remain ongoing challenges. The present study addressed these problems using simultaneous EEG-fMRI and a specific inattentional blindness paradigm with three physically identical phases in female and male human participants. In phase 1, participants performed a distractor task during which line drawings of faces and control stimuli were presented centrally. While some participants spontaneously noticed the faces in phase 1, others remained inattentionally blind. In phase 2, all participants were made aware of the task-irrelevant faces but continued the distractor task. In phase 3, the faces became task-relevant. Bayesian analysis of brain responses demonstrated that conscious face perception was most strongly associated with activation in fusiform gyrus (fMRI) as well as the N170 and visual awareness negativity (EEG). Smaller awareness effects were revealed in the occipital and prefrontal cortex (fMRI). Task-relevant face processing, on the other hand, led to strong, extensive activation of occipitotemporal, frontoparietal, and attentional networks (fMRI). In EEG, it enhanced early negativities and elicited a pronounced P3b component. Overall, we provide evidence that conscious visual perception is linked with early processing in stimulus-specific sensory brain areas but may additionally involve prefrontal cortex. In contrast, the strong activation of widespread brain networks and the P3b are more likely associated with task-related processes.SIGNIFICANCE STATEMENT How does our brain generate visual consciousness-the subjective experience of what it is like to see, for example, a face? To date, it is hotly debated whether it emerges early in sensory brain regions or later when a widespread frontoparietal network is activated. Here, we use simultaneous fMRI and EEG for high spatial and temporal resolution and demonstrate that conscious face perception is predominantly linked to early and occipitotemporal processes, but also prefrontal activity. Task-related processes (e.g., decision-making), on the other hand, elicit brain-wide activations including late and strong frontoparietal activity. These findings challenge numerous previous studies and highlight the importance of investigating the neural correlates of consciousness in the absence of task relevance.

Stimulus arousal drives amygdalar responses to emotional expressions across sensory modalities.

The factors that drive amygdalar responses to emotionally significant stimuli are still a matter of debate - particularly the proneness of the amygdala to respond to negatively-valenced stimuli has been discussed controversially. Furthermore, it is uncertain whether the amygdala responds in a modality-general fashion or whether modality-specific idiosyncrasies exist. Therefore, the present functional magnetic resonance imaging (fMRI) study systematically investigated amygdalar responding to stimulus valence and arousal of emotional expressions across visual and auditory modalities. During scanning, participants performed a gender judgment task while prosodic and facial emotional expressions were presented. The stimuli varied in stimulus valence and arousal by including neutral, happy and angry expressions of high and low emotional intensity. Results demonstrate amygdalar activation as a function of stimulus arousal and accordingly associated emotional intensity regardless of stimulus valence. Furthermore, arousal-driven amygdalar responding did not depend on the visual and auditory modalities of emotional expressions. Thus, the current results are consistent with the notion that the amygdala codes general stimulus relevance across visual and auditory modalities irrespective of valence. In addition, whole brain analyses revealed that effects in visual and auditory areas were driven mainly by high intense emotional facial and vocal stimuli, respectively, suggesting modality-specific representations of emotional expressions in auditory and visual cortices.

Early brain responses to affective faces: A simultaneous EEG-fMRI study.

The spatio-temporal neural basis of earliest differentiation between emotional and neutral facial expressions is a matter of debate. The present study used concurrent electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) in order to investigate the 'when' and 'where' of earliest prioritization of emotional over neutral expressions. We measured event-related potentials (ERPs) and blood oxygen dependent (BOLD) signal changes in response to facial expressions of varying emotional intensity and different valence categories. Facial expressions were presented superimposed by two horizontal bars and participants engaged in a focal bars task (low load, high load), in order to manipulate the availability of attentional resources during face perception. EEG data revealed the earliest expression effects in the P1 range (76-128 ms) as a parametric function of stimulus arousal independent of load conditions. Conventional fMRI data analysis also demonstrated significant modulations as a function of stimulus arousal, independent of load, in amygdala, superior temporal sulcus, fusiform gyrus and lateral occipital cortex. Correspondingly, EEG-informed fMRI analysis revealed a significant positive correlation between single-trial P1 amplitudes and BOLD responses in amygdala and lateral posterior occipital cortex. Our results are in line with the hypothesis of the amygdala as fast responding relevance detector and corresponding effects in early visual face processing areas across facial expressions and load conditions.

Effects of emotional intensity under perceptual load: An event-related potentials (ERPs) study.

Effects of emotional intensity and valence on visual event-related potentials (ERPs) are still poorly understood, in particular in the context of limited attentional resources. In the present EEG study, we investigated the effect of emotional intensity of different emotional facial expressions on P1, N170, early posterior negativity (EPN) and late positive potential (LPP) while varying the amount of available attentional resources. A new stimulus set comprising 90 full color pictures of neutral, happy (low, high intensity), and angry (low, high intensity) expressions was developed. These facial expressions were presented centrally, superimposed by two horizontal bars, and participants engaged in a focal bars task. Availability of attentional resources was varied in two conditions by manipulating the difficulty of the focal bars task (low vs. high perceptual load). Our findings demonstrate intensity and valence effects of task-irrelevant facial expressions on early (N170) and intermediate processing stages (EPN). In addition, task-related effects of perceptual load evolved at intermediate processing stages and were full blown in the time window of LPP. In line with limited resource accounts, valence effects on N170 and EPN were reduced under high perceptual load. Interestingly, apart from this valence by load interaction no further interactions between stimulus and task-driven factors were obtained: Effects of emotional intensity were not modulated by the perceptual load of the focal bars task, indicating that emotional intensity was processed even though attentional resources were heavily restricted.