Rising early warning signals in affect associated with future changes in depression: a dynamical systems approach.

BACKGROUND: Predicting future states of psychopathology such as depressive episodes has been a hallmark initiative in mental health research. Dynamical systems theory has proposed that rises in certain 'early warning signals' (EWSs) in time-series data (e.g. auto-correlation, temporal variance, network connectivity) may precede impending changes in disorder severity. The current study investigates whether rises in these EWSs over time are associated with future changes in disorder severity among a group of patients with major depressive disorder (MDD). METHODS: Thirty-one patients with MDD completed the study, which consisted of daily smartphone-delivered surveys over 8 weeks. Daily positive and negative affect were collected for the time-series analyses. A rolling window approach was used to determine whether rises in auto-correlation of total affect, temporal standard deviation of total affect, and overall network connectivity in individual affect items were predictive of increases in depression symptoms. RESULTS: Results suggested that rises in auto-correlation were significantly associated with worsening in depression symptoms (r = 0.41, p = 0.02). Results indicated that neither rises in temporal standard deviation (r = -0.23, p = 0.23) nor in network connectivity (r = -0.12, p = 0.59) were associated with changes in depression symptoms. CONCLUSIONS: This study more rigorously examines whether rises in EWSs were associated with future depression symptoms in a larger group of patients with MDD. Results indicated that rises in auto-correlation were the only EWS that was associated with worsening future changes in depression.

Stress measurement using speech: Recent advancements, validation issues, and ethical and privacy considerations.

Life stress is a well-established risk factor for a variety of mental and physical health problems, including anxiety disorders, depression, chronic pain, heart disease, asthma, autoimmune diseases, and neurodegenerative disorders. The purpose of this article is to describe emerging approaches for assessing stress using speech, which we do by reviewing the methodological advantages of these digital health tools, and the validation, ethical, and privacy issues raised by these technologies. As we describe, it is now possible to assess stress via the speech signal using smartphones and smart speakers that employ software programs and artificial intelligence to analyze several features of speech and speech acoustics, including pitch, jitter, energy, rate, and length and number of pauses. Because these digital devices are ubiquitous, we can now assess individuals' stress levels in real time in almost any natural environment in which people speak. These technologies thus have great potential for advancing digital health initiatives that involve continuously monitoring changes in psychosocial functioning and disease risk over time. However, speech-based indices of stress have yet to be well-validated against stress biomarkers (e.g., cortisol, cytokines) that predict disease risk. In addition, acquiring speech samples raises the possibility that conversations intended to be private could one day be made public; moreover, obtaining real-time psychosocial risk information prompts ethical questions regarding how these data should be used for medical, commercial, and personal purposes. Although assessing stress using speech thus has enormous potential, there are critical validation, privacy, and ethical issues that must be addressed.

Use of In-Game Rewards to Motivate Daily Self-Report Compliance: Randomized Controlled Trial.

BACKGROUND: Encouraging individuals to report daily information such as unpleasant disease symptoms, daily activities and behaviors, or aspects of their physical and emotional state is difficult but necessary for many studies and clinical trials that rely on patient-reported data as primary outcomes. Use of paper diaries is the traditional method of completing daily diaries, but digital surveys are becoming the new standard because of their increased compliance; however, they still fall short of desired compliance levels. OBJECTIVE: Mobile games using in-game rewards offer the opportunity to increase compliance above the rates of digital diaries and paper diaries. We conducted a 5-week randomized control trial to compare the completion rates of a daily diary across 3 conditions: a paper-based participant-reported outcome diary (Paper PRO), an electronic-based participant-reported outcome diary (ePRO), and a novel ePRO diary with in-game rewards (Game-Motivated ePRO). METHODS: We developed a novel mobile game that is a combination of the idle and pet collection genres to reward individuals who complete a daily diary with an in-game reward. Overall, 197 individuals aged 6 to 24 years (male: 100 and female: 97) were enrolled in a 5-week study after being randomized into 1 of the 3 methods of daily diary completion. Moreover, 157 participants (male: 84 and female: 69) completed at least one diary and were subsequently included in analysis of compliance rates. RESULTS: We observed a significant difference (F2,124=6.341; P=.002) in compliance to filling out daily diaries, with the Game-Motivated ePRO group having the highest compliance (mean completion 86.4%, SD 19.6%), followed by the ePRO group (mean completion 77.7%, SD 24.1%), and finally, the Paper PRO group (mean completion 70.6%, SD 23.4%). The Game-Motivated ePRO (P=.002) significantly improved compliance rates above the Paper PRO. In addition, the Game-Motivated ePRO resulted in higher compliance rates than the rates of ePRO alone (P=.09). Equally important, even though we observed significant differences in completion of daily diaries between groups, we did not observe any statistically significant differences in association between the responses to a daily mood question and study group, the average diary completion time (P=.52), or the System Usability Scale score (P=.88). CONCLUSIONS: The Game-Motivated ePRO system encouraged individuals to complete the daily diaries above the compliance rates of the Paper PRO and ePRO without altering the participants' responses. TRIAL REGISTRATION: ClinicalTrials.gov NCT03738254; http://clinicaltrials.gov/ct2/show/NCT03738254 (Archived by WebCite at http://www.webcitation.org/74T1p8u52).

Digital phenotyping of suicidal thoughts.

BACKGROUND: To examine whether there are subtypes of suicidal thinking using real-time digital monitoring, which allows for the measurement of such thoughts with greater temporal granularity than ever before possible. METHODS: We used smartphone-based real-time monitoring to assess suicidal thoughts four times per day in two samples: Adults who attempted suicide in the past year recruited from online forums (n = 51 participants with a total of 2,889 responses, surveyed over 28 days; ages ranged from 18 to 38 years) and psychiatric inpatients with recent suicidal ideation or attempts (n = 32 participants with a total of 640 responses, surveyed over the duration of inpatient treatment [mean stay = 8.79 days], ages ranged 23-68 years). Latent profile analyses were used to identify distinct phenotypes of suicidal thinking based on the frequency, intensity, and variability of such thoughts. RESULTS: Across both samples, five distinct phenotypes of suicidal thinking emerged that differed primarily on the intensity and variability of suicidal thoughts. Participants whose profile was characterized by more severe, persistent suicidal thoughts (i.e., higher mean and lower variability around the mean) were most likely to have made a recent suicide attempt. CONCLUSIONS: Suicidal thinking has historically been studied as a homogeneous construct, but using newly available monitoring technology we discovered five profiles of suicidal thinking. Key questions for future research include how these phenotypes prospectively relate to future suicidal behaviors, and whether they represent remain stable or trait-like over longer periods.

QuantifyMe: An Open-Source Automated Single-Case Experimental Design Platform.

Smartphones and wearable sensors have enabled unprecedented data collection, with many products now providing feedback to users about recommended step counts or sleep durations. However, these recommendations do not provide personalized insights that have been shown to be best suited for a specific individual. A scientific way to find individualized recommendations and causal links is to conduct experiments using single-case experimental design; however, properly designed single-case experiments are not easy to conduct on oneself. We designed, developed, and evaluated a novel platform, QuantifyMe, for novice self-experimenters to conduct proper-methodology single-case self-experiments in an automated and scientific manner using their smartphones. We provide software for the platform that we used (available for free on GitHub), which provides the methodological elements to run many kinds of customized studies. In this work, we evaluate its use with four different kinds of personalized investigations, examining how variables such as sleep duration and regularity, activity, and leisure time affect personal happiness, stress, productivity, and sleep efficiency. We conducted a six-week pilot study (N = 13) to evaluate QuantifyMe. We describe the lessons learned developing the platform and recommendations for its improvement, as well as its potential for enabling personalized insights to be scientifically evaluated in many individuals, reducing the high administrative cost for advancing human health and wellbeing.

Multicenter clinical assessment of improved wearable multimodal convulsive seizure detectors.

OBJECTIVE: New devices are needed for monitoring seizures, especially those associated with sudden unexpected death in epilepsy (SUDEP). They must be unobtrusive and automated, and provide false alarm rates (FARs) bearable in everyday life. This study quantifies the performance of new multimodal wrist-worn convulsive seizure detectors. METHODS: Hand-annotated video-electroencephalographic seizure events were collected from 69 patients at six clinical sites. Three different wristbands were used to record electrodermal activity (EDA) and accelerometer (ACM) signals, obtaining 5,928 h of data, including 55 convulsive epileptic seizures (six focal tonic-clonic seizures and 49 focal to bilateral tonic-clonic seizures) from 22 patients. Recordings were analyzed offline to train and test two new machine learning classifiers and a published classifier based on EDA and ACM. Moreover, wristband data were analyzed to estimate seizure-motion duration and autonomic responses. RESULTS: The two novel classifiers consistently outperformed the previous detector. The most efficient (Classifier III) yielded sensitivity of 94.55%, and an FAR of 0.2 events/day. No nocturnal seizures were missed. Most patients had <1 false alarm every 4 days, with an FAR below their seizure frequency. When increasing the sensitivity to 100% (no missed seizures), the FAR is up to 13 times lower than with the previous detector. Furthermore, all detections occurred before the seizure ended, providing reasonable latency (median = 29.3 s, range = 14.8-151 s). Automatically estimated seizure durations were correlated with true durations, enabling reliable annotations. Finally, EDA measurements confirmed the presence of postictal autonomic dysfunction, exhibiting a significant rise in 73% of the convulsive seizures. SIGNIFICANCE: The proposed multimodal wrist-worn convulsive seizure detectors provide seizure counts that are more accurate than previous automated detectors and typical patient self-reports, while maintaining a tolerable FAR for ambulatory monitoring. Furthermore, the multimodal system provides an objective description of motor behavior and autonomic dysfunction, aimed at enriching seizure characterization, with potential utility for SUDEP warning.

Efficacy of a Web-based, crowdsourced peer-to-peer cognitive reappraisal platform for depression: randomized controlled trial.

BACKGROUND: Self-guided, Web-based interventions for depression show promising results but suffer from high attrition and low user engagement. Online peer support networks can be highly engaging, but they show mixed results and lack evidence-based content. OBJECTIVE: Our aim was to introduce and evaluate a novel Web-based, peer-to-peer cognitive reappraisal platform designed to promote evidence-based techniques, with the hypotheses that (1) repeated use of the platform increases reappraisal and reduces depression and (2) that the social, crowdsourced interactions enhance engagement. METHODS: Participants aged 18-35 were recruited online and were randomly assigned to the treatment group, "Panoply" (n=84), or an active control group, online expressive writing (n=82). Both are fully automated Web-based platforms. Participants were asked to use their assigned platform for a minimum of 25 minutes per week for 3 weeks. Both platforms involved posting descriptions of stressful thoughts and situations. Participants on the Panoply platform additionally received crowdsourced reappraisal support immediately after submitting a post (median response time=9 minutes). Panoply participants could also practice reappraising stressful situations submitted by other users. Online questionnaires administered at baseline and 3 weeks assessed depression symptoms, reappraisal, and perseverative thinking. Engagement was assessed through self-report measures, session data, and activity levels. RESULTS: The Panoply platform produced significant improvements from pre to post for depression (P=.001), reappraisal (P<.001), and perseverative thinking (P<.001). The expressive writing platform yielded significant pre to post improvements for depression (P=.02) and perseverative thinking (P<.001), but not reappraisal (P=.45). The two groups did not diverge significantly at post-test on measures of depression or perseverative thinking, though Panoply users had significantly higher reappraisal scores (P=.02) than expressive writing. We also found significant group by treatment interactions. Individuals with elevated depression symptoms showed greater comparative benefit from Panoply for depression (P=.02) and perseverative thinking (P=.008). Individuals with baseline reappraisal deficits showed greater comparative benefit from Panoply for depression (P=.002) and perseverative thinking (P=.002). Changes in reappraisal mediated the effects of Panoply, but not the expressive writing platform, for both outcomes of depression (ab=-1.04, SE 0.58, 95% CI -2.67 to -.12) and perseverative thinking (ab=-1.02, SE 0.61, 95% CI -2.88 to -.20). Dropout rates were similar for the two platforms; however, Panoply yielded significantly more usage activity (P<.001) and significantly greater user experience scores (P<.001). CONCLUSIONS: Panoply engaged its users and was especially helpful for depressed individuals and for those who might ordinarily underutilize reappraisal techniques. Further investigation is needed to examine the long-term effects of such a platform and whether the benefits generalize to a more diverse population of users. TRIAL REGISTRATION: ClinicalTrials.gov NCT02302248; https://clinicaltrials.gov/ct2/show/NCT02302248 (Archived by WebCite at http://www.webcitation.org/6Wtkj6CXU).

ReCANVo: A database of real-world communicative and affective nonverbal vocalizations.

Nonverbal vocalizations, such as sighs, grunts, and yells, are informative expressions within typical verbal speech. Likewise, individuals who produce 0-10 spoken words or word approximations ("minimally speaking" individuals) convey rich affective and communicative information through nonverbal vocalizations even without verbal speech. Yet, despite their rich content, little to no data exists on the vocal expressions of this population. Here, we present ReCANVo: Real-World Communicative and Affective Nonverbal Vocalizations - a novel dataset of non-speech vocalizations labeled by function from minimally speaking individuals. The ReCANVo database contains over 7000 vocalizations spanning communicative and affective functions from eight minimally speaking individuals, along with communication profiles for each participant. Vocalizations were recorded in real-world settings and labeled in real-time by a close family member who knew the communicator well and had access to contextual information while labeling. ReCANVo is a novel database of nonverbal vocalizations from minimally speaking individuals, the largest available dataset of nonverbal vocalizations, and one of the only affective speech datasets collected amidst daily life across contexts.

A Robotic Companion for Psychological Well-being: A Long-term Investigation of Companionship and Therapeutic Alliance.

Social support plays a crucial role in managing and enhancing one's mental health and well-being. In order to explore the role of a robot's companion-like behavior on its therapeutic interventions, we conducted an eight-week-long deployment study with seventy participants to compare the impact of (1) a control robot with only assistant-like skills, (2) a coach-like robot with additional instructive positive psychology interventions, and (3) a companion-like robot that delivered the same interventions in a peer-like and supportive manner. The companion-like robot was shown to be the most effective in building a positive therapeutic alliance with people, enhancing participants' well-being and readiness for change. Our work offers valuable insights into how companion AI agents could further enhance the efficacy of the mental health interventions by strengthening their therapeutic alliance with people for long-term mental health support.

Real-time digital monitoring of a suicide attempt by a hospital patient.

Suicide is among the most devastating problems facing clinicians, who currently have limited tools to predict and prevent suicidal behavior. Here we report on real-time, continuous smartphone and sensor data collected before, during, and after a suicide attempt made by a patient during a psychiatric inpatient hospitalization. We observed elevated and persistent sympathetic nervous system arousal and suicidal thinking leading up to the suicide attempt. This case provides the highest resolution data to date on the psychological, psychophysiological, and behavioral markers of imminent suicidal behavior and highlights new directions for prediction and prevention efforts.

Interventions to Modify Psychological Well-Being: Progress, Promises, and an Agenda for Future Research.

Psychological well-being, characterized by feelings, cognitions, and strategies that are associated with positive functioning (including hedonic and eudaimonic well-being), has been linked with better physical health and greater longevity. Importantly, psychological well-being can be strengthened with interventions, providing a strategy for improving population health. But are the effects of well-being interventions meaningful, durable, and scalable enough to improve health at a population-level? To assess this possibility, a cross-disciplinary group of scholars convened to review current knowledge and develop a research agenda. Here we summarize and build on the key insights from this convening, which were: (1) existing interventions should continue to be adapted to achieve a large-enough effect to result in downstream improvements in psychological functioning and health, (2) research should determine the durability of interventions needed to drive population-level and lasting changes, (3) a shift from individual-level care and treatment to a public-health model of population-level prevention is needed and will require new infrastructure that can deliver interventions at scale, (4) interventions should be accessible and effective in racially, ethnically, and geographically diverse samples. A discussion examining the key future research questions follows.

Convulsive seizure detection using a wrist-worn electrodermal activity and accelerometry biosensor.

The special requirements for a seizure detector suitable for everyday use in terms of cost, comfort, and social acceptance call for alternatives to electroencephalography (EEG)-based methods. Therefore, we developed an algorithm for automatic detection of generalized tonic-clonic (GTC) seizures based on sympathetically mediated electrodermal activity (EDA) and accelerometry measured using a novel wrist-worn biosensor. The problem of GTC seizure detection was posed as a supervised learning task in which the goal was to classify 10-s epochs as a seizure or nonseizure event based on 19 extracted features from EDA and accelerometry recordings using a Support Vector Machine. Performance was evaluated using a double cross-validation method. The new seizure detection algorithm was tested on >4,213 h of recordings from 80 patients and detected 15 (94%) of 16 of the GTC seizures from seven patients with 130 false alarms (0.74 per 24 h). This algorithm can potentially provide a convulsive seizure alarm system for caregivers and objective quantification of seizure frequency.

Smartwatch biomarkers and the path to clinical use.

Wearables have advanced from collecting consumer-quality fitness data to collecting continuous clinical-quality physiology that, when processed carefully, can identify medically significant events. In a recent issue of Nature Medicine, Dunn et al.1 described how vital signs from wearables predict clinical laboratory blood- and urine-based measurements better than vital signs measured in the clinic.

Guidelines for Conducting Ethical Artificial Intelligence Research in Neurology: A Systematic Approach for Clinicians and Researchers.

Preemptive recognition of the ethical implications of study design and algorithm choices in artificial intelligence (AI) research is an important but challenging process. AI applications have begun to transition from a promising future to clinical reality in neurology. As the clinical management of neurology is often concerned with discrete, often unpredictable, and highly consequential events linked to multimodal data streams over long timescales, forthcoming advances in AI have great potential to transform care for patients. However, critical ethical questions have been raised with implementation of the first AI applications in clinical practice. Clearly, AI will have far-reaching potential to promote, but also to endanger, ethical clinical practice. This article employs an anticipatory ethics approach to scrutinize how researchers in neurology can methodically identify ethical ramifications of design choices early in the research and development process, with a goal of preempting unintended consequences that may violate principles of ethical clinical care. First, we discuss the use of a systematic framework for researchers to identify ethical ramifications of various study design and algorithm choices. Second, using epilepsy as a paradigmatic example, anticipatory clinical scenarios that illustrate unintended ethical consequences are discussed, and failure points in each scenario evaluated. Third, we provide practical recommendations for understanding and addressing ethical ramifications early in methods development stages. Awareness of the ethical implications of study design and algorithm choices that may unintentionally enter AI is crucial to ensuring that incorporation of AI into neurology care leads to patient benefit rather than harm.

Sleep assessment by means of a wrist actigraphy-based algorithm: agreement with polysomnography in an ambulatory study on older adults.

The purpose of the present work is to examine, on a clinically diverse population of older adults (N = 46) sleeping at home, the performance of two actigraphy-based sleep tracking algorithms (i.e., Actigraphy-based Sleep algorithm, ACT-S1 and Sadeh's algorithm) compared to manually scored electroencephalography-based PSG (PSG-EEG). ACT-S1 allows for a fully automatic identification of sleep period time (SPT) and within the identified sleep period, the sleep-wake classification. SPT detected by ACT-S1 did not differ statistically from using PSG-EEG (bias = -9.98 min; correlation 0.89). In sleep-wake classification on 30-s epochs within the identified sleep period, the new ACT-S1 presented similar or slightly higher accuracy (83-87%), precision (86-89%) and F1 score (90-92%), significantly higher specificity (39-40%), and significantly lower, but still high, sensitivity (96-97%) compared to Sadeh's algorithm, which achieved 99% sensitivity as the only measure better than ACT-S1's. Total sleep times (TST) estimated with ACT-S1 and Sadeh's algorithm were higher, but still highly correlated to PSG-EEG's TST. Sleep quality metrics of sleep period efficiency and wake-after-sleep-onset computed by ACT-S1 were not significantly different from PSG-EEG, while the same sleep quality metrics derived by Sadeh's algorithm differed significantly from PSG-EEG. Agreement between ACT-S1 and PSG-EEG reached was highest when analyzing the subset of subjects with least disrupted sleep (N = 28). These results provide evidence of promising performance of a full-automation of the sleep tracking procedure with ACT-S1 on older adults. Future longitudinal validations across specific medical conditions are needed. The algorithm's performance may further improve with integrating multi-sensor information.

Consensus Statement on Ethical & Safety Practices for Conducting Digital Monitoring Studies with People at Risk of Suicide and Related Behaviors.

OBJECTIVE: Digital monitoring technologies (e.g., smart-phones and wearable devices) provide unprecedented opportunities to study potentially harmful behaviors such as suicide, violence, and alcohol/substance use in real-time. The use of these new technologies has the potential to significantly advance the understanding, prediction, and prevention of these behaviors. However, such technologies also introduce myriad ethical and safety concerns, such as deciding when and how to intervene if a participant's responses indicate elevated risk during the study? METHODS: We used a modified Delphi process to develop a consensus among a diverse panel of experts on the ethical and safety practices for conducting digital monitoring studies with those at risk for suicide and related behaviors. Twenty-four experts including scientists, clinicians, ethicists, legal experts, and those with lived experience provided input into an iterative, multi-stage survey, and discussion process. RESULTS: Consensus was reached on multiple aspects of such studies, including: inclusion criteria, informed consent elements, technical and safety procedures, data review practices during the study, responding to various levels of participant risk in real-time, and data and safety monitoring. CONCLUSIONS: This consensus statement provides guidance for researchers, funding agencies, and institutional review boards regarding expert views on current best practices for conducting digital monitoring studies with those at risk for suicide-with relevance to the study of a range of other potentially harmful behaviors (e.g., alcohol/substance use and violence). This statement also highlights areas in which more data are needed before consensus can be reached regarding best ethical and safety practices for digital monitoring studies.