Posttraumatic stress disorder (PTSD) is a psychiatric condition that may develop after trauma exposure. PTSD is characterized by considerable clinical heterogeneity. The amygdala's key role in fear conditioning makes it an important focus for investigating the neurobiology of PTSD. However, associations between amygdala volume and PTSD have been inconsistent. The amygdala consists of functionally distinct nuclei. Specific associations between amygdala nuclei volumes and PTSD may account for previous discrepancies between PTSD and whole amygdala volume. This study investigates the associations between amygdala nuclei volumes, PTSD diagnosis, severity, symptom cluster scores, age of onset and childhood trauma. Individuals with a PTSD diagnosis (n = 771) and controls (n = 1 081, 72% trauma-exposed) were sourced from the Enhancing Neuro-Imaging Genetics through Meta-Analysis and Psychiatric Genomics Consortium (mean age = 32.4 years, (SD = 13 years), 60% male). Nine amygdala nuclei volumes were compared to PTSD diagnosis, age of onset, overall severity, symptom cluster scores (re-experiencing, arousal, and avoidance/emotional numbing), and childhood trauma subscales. Analyses were performed using ordinary least-squares regression, corrected for age, sex, intracranial volume, and whole amygdala volume. PTSD diagnosis was not significantly associated with amygdala nuclei volumes. PTSD severity scores were associated with smaller right lateral nucleus volume (β = -0.26, pBON = 0.01). Smaller right lateral nucleus volume was also associated with re-experiencing (β = -1.01, pBON = 0.04) and arousal (β = -0.9, pBON = 0.04), smaller left paralaminar nucleus volume was associated with re-experiencing (β = -0.1, pBON = 0.04), smaller left corticoamygdaloid transition area volume was associated with avoidance (β = -0.31, pBON = 0.02). Larger left and right central nucleus volumes were significantly associated with childhood physical abuse (β = 0.24, pBON = 9 × 10-3) and neglect (β = 0.29, pBON = 0.04), respectively. Differences in select amygdala nuclei volumes among adults are associated with PTSD severity, symptom cluster scores, and childhood physical abuse and neglect. These findings demonstrate nuclei-specific patterns consistent with their functional roles in fear learning and expression.

Background: Digital meditation-based interventions (MBIs) reach vast global audiences with millions of active users, yet concerns persist about the frequency and nature of adverse experiences (ie, AExs) occurring during meditation training. Some researchers have argued that AExs are substantially underdetected and reflect iatrogenic harm caused by meditation (ie, adverse effects [AEfs]). Others contend that these experiences largely reflect common stressors that would be experienced without meditation. These competing perspectives underscore the need for further research, particularly in the context of digital MBIs, the most widely used form of meditation training. Objective: This study examined the prevalence, predictors, and subjective evaluations of AExs during a digital MBI and tested whether reported experiences may be caused by meditation practice via comparisons between meditation-exposed and nonexposed participants. Methods: Data were drawn from 2 trials of the Healthy Minds Program. Exploratory study 1 (n=315) consisted of a sample of distressed US undergraduate students to estimate the prevalence of AExs and identify baseline predictors. Preregistered confirmatory study 2 (n=594) sampled distressed US adults from all 50 states to replicate findings from study 1 and to examine participants' subjective evaluations of AExs. Study 2 additionally compared AEx rates between participants who did and did not complete guided meditations to assess whether AExs could be caused by meditation exposure. Study 3 (n=87) used qualitative methods to analyze study 1 participants' responses to an open-ended question regarding their strategies for coping with AExs. Results: In studies 1 and 2, 27.9% (88/315) and 10.1% (40/396) of participants, respectively, reported at least one AEx during the study period, with 6.7% (21/315) and 3% (12/396) reporting functional impairment, largely aligning with previous research. Critically, in study 2, rates of AExs did not significantly differ between participants who did and did not complete guided meditations, suggesting that these experiences were not caused by meditation practice. Higher baseline depression,anxiety, loneliness, experiential avoidance, and perceived barriers to meditation predicted more frequent AExs. In studies 1 and 2, 89.8% (79/88) and 90% (36/40) of participants who reported AExs, respectively, indicated that they were glad to have learned to meditate. Qualitative analyses showed that participants used diverse coping strategies, often using skills learned through the Healthy Minds Program. Conclusions: AExs were relatively common but occurred at comparable rates among participants who did and did not meditate, challenging claims that such experiences were caused by meditation practice in distressed individuals. Although a small subset of participants reported some degree of functional impairment, most evaluated their AExs as tolerable and described their overall MBI experience as positive. Together, these findings highlight the importance of distinguishing AExs that likely reflect epiphenomena of preexisting distress or symptoms from iatrogenic harm attributable to MBIs. Trial Registration: Study 1: ClinicalTrials.gov NCT04741529; https://clinicaltrials.gov/study/NCT04741529; Study 2: ClinicalTrials.gov NCT06282523; https://clinicaltrials.gov/study/NCT06282523

This study assessed relations between white matter microstructure at one month of age and visuospatial processing abilities at six months of age. Participants included ninety-one infants (n = 48 female) born after singleton non-complicated pregnancy. The infants underwent MRI at one month of age and a behavioral assessment at six months of age. Results revealed that the intensity of toy play was associated with fractional anisotropy (FA) of the right (t = 3.002, adjusted p = 0.038) and left superior cerebellar peduncle (t = 2.799, adjusted p = 0.038) and right cingulate gyrus (t = 2.908, adjusted p = 0.0038) while Gaze Shifting was associated with mean diffusivity and axial diffusivity of the right superior cerebellar peduncle (t = 3.099, adjusted p = 0.048). No other correlations, including those studied interactions with biological sex, were significant after adjusting for multiple comparisons. The findings support the notion that developing white matter microstructure, as measured by diffusion MRI metrics, plays a role in the development of visuospatial processing. Future studies should explore how these relationships develop and predict visuospatial ability and working memory later in life.

Despite decades of meditation research, there is a lack of preregistered and well-powered studies that investigate the effects of brief meditation practices on subjective wellbeing and use data-driven approaches to predict response to these interventions. Using representative samples of the US and UK adult populations with regards to age, sex, and ethnicity (N = 5049), we conducted a preregistered and well-powered randomized controlled trial to investigate the effects of three brief (5-10 min) meditation practices (i.e., mindfulness, self-compassion, gratitude) relative to a control condition. We also examined whether a data-driven approach can predict an individual's response to these interventions from their pre-intervention characteristics. Taken together, our findings suggest that brief meditation practices modestly improve an aspect of subjective wellbeing (negative affect) and such response can be predicted using pre-intervention characteristics. Future prospective randomized trials should examine algorithm-guided intervention assignment to directly test the potential of personalized meditation recommendations to improve subjective wellbeing.

We present a dynamical-systems based model for resting-state functional magnetic resonance imaging (rs-fMRI), trained on a dataset of roughly $40$K rs-fMRI sequences covering a wide variety of public and available-by-permission datasets. While most existing proposals use transformer backbones, we utilize multi-resolution temporal modeling of the dynamics across parcellated brain regions. We show that MnemoDyn is compute efficient and generalizes very well across diverse populations and scanning protocols. When benchmarked against current state-of-the-art transformer-based approaches, MnemoDyn consistently delivers superior reconstruction quality. Overall, we find that with such large-scale pre-training on (non-proprietary) rs-fMRI datasets, we get a highly performant model for various downstream tasks. Our results also provide evidence of the efficacy of the model on small sample size studies which has implications for neuroimaging studies at large where resting state fMRI is a commonly acquired imaging modality.

Background: Children living in conflict zones experience high levels of psychological distress. Schools can provide an accessible setting for support, yet evidence on the effectiveness of school-based interventions in active war contexts remains limited. Objectives: To evaluate children’s well-being and internal coping resources during the war in Ukraine and to examine the feasibility of a school-based program designed to enhance psychological well-being in preadolescents. Participants and setting: The study involved 81 children aged 10–12 years from schools in Lviv, Ukraine. Methods: Adverse Childhood Experiences (ACEs), PTSD symptoms, quality of life, self-compassion, and mindfulness traits were assessed using standard questionnaires and validated psychometric scales. The intervention program, delivered at school, focused on mindfulness, self-compassion, social connection, sense of purpose, and trauma processing. Acceptability and perceived impact were evaluated post-intervention among children, families, and school staff. Results: 42% of children reported four or more ACEs. 39.5% of children exceeded the clinical cutoff for probable PTSD on the CRIES-8 scale, with differences observed between boys and girls. Higher levels of self-compassion and mindfulness were associated with lower PTSD symptoms. Children, families, and school staff reported improvements in children’s well-being, emotion regulation, and social functioning after the intervention. Conclusions: Self-compassion and mindfulness training may serve as protective factors against PTSD. Our findings provide encouraging preliminary evidence supporting the potential of a school-based intervention to promote children’s psychological well-being in an ongoing war setting. Future studies with larger samples, control groups, and objective measures will help strengthen the generalizability of these findings.

Personal digital devices are transforming mental health assessment. Leveraging the ubiquity of smartphones and public familiarity with smartphone-recorded “selfies,” we developed a novel “video selfie” ecological momentary assessment, and tested the utility of digital biomarkers to improve prediction of mental health and well-being in a sample of non-clinical participants. Our video selfie paradigm yielding 71,902 videos (N = 1,634 participants) demonstrated high feasibility, indicated by high adherence (77% mean response rate) and high video quality with 92% of recordings meeting quality criteria. We show that video selfies demonstrate incremental validity beyond conventional self-report ecological momentary assessment, with video-based multimodal features collectively improving model performance for predicting concurrent NIH PROMIS scores for anxiety and depression and flourishing (Flourishing Index) (5.2%-7.0%). This research lays the groundwork for methodological innovation that advances mental health and well-being “in-the-wild” and at scale. Future applications include the integration of video-based data streams to improve time-sensitive delivery of digitally-mediated mental health interventions. ​

[This corrects the article DOI: 10.1371/journal.pone.0299352.].

Depression is a complex disorder for which there is growing interest in identifying objective behavioral markers that measure precise symptoms, such as anhedonia and blunted emotional reactivity. This study explores the feasibility of using smile and smirk expression dynamics, captured through our novel stimulus-based mobile affective probe, as candidate digital biomarkers of depression severity within a large-scale mobile health intervention trial, BeWell. Data from 684 BeWell participants (2,702 observations) are analyzed longitudinally for 16 weeks, comparing their PHQ-8 survey scores with their facial responses to short videos intended to elicit smiles. Mixed-effects models reveal that higher maximum Duchenne smile intensity in reaction to liked stimuli is associated with lower depression scores over time at both within- and between-person levels. We additionally share insights from our tool, including ease of use, perceptions of the stimulus, and technical challenges, which offer considerations for the future development of stimulus-based affect probes in real-world settings.

Mind–body interventions such as mindfulness-based stress reduction (MBSR) may improve well-being by increasing awareness and regulation of physiological and cognitive states. However, it is unclear how practice may alter long-term, baseline physiological processes, and whether these changes reflect improved well-being. Using respiration rate (RR), which can be sensitive to effects of meditation, and 3 aspects of self-reported well-being (psychological well-being [PWB], distress, and medical symptoms), we tested pre-registered hypotheses that: (1) Lower baseline RR (in a resting, non-meditative state) would be a physiological marker associated with well-being, (2) MBSR would decrease RR, and (3) Training-related decreases in RR would be associated with improved well-being. We recruited 245 adults (age range = 18–65, M = 42.4): experienced meditators (n = 42), and meditation-naïve participants randomized to MBSR (n = 72), active control (n = 41), or waitlist control (n = 66). Data were collected at pre-randomization, post-intervention (or waiting), and long-term follow-up. Lower baseline RR was associated with lower psychological distress among long-term meditators (p* = 0.03, b = 0.02, 95% CI [0.01, 0.03]), though not in non-meditators prior to training. MBSR decreased RR compared to waitlist (p = 0.02, Cohen’s d = − 0.41, 95% CI [− 0.78, − 0.06]), but not the active control. Decreased RR related to decreased medical symptoms, across all participants (p* = 0.02, b = 0.57, 95% CI [0.15, 0.98]). Post-training, lower RR was associated with higher PWB across training groups compared to waitlist (p* = 0.01, b = 0.06, 95% CI [0.02, 0.10]), though there were no significant differences in change in PWB between groups. This physiological marker may indicate higher physical and/or psychological well-being in those who engage in wellness practices.

Resident burnout harms learning and negatively affects patient care, physician retention, and healthcare costs. Programs are increasingly prioritizing resident well-being. However, literature focuses on resident burnout, often overlooking well-being, and post-pandemic well-being has not been evaluated across specialties. This study assessed post-pandemic burnout and well-being among frontline residents nationwide and examined associations with demographics. A nationwide, cross-sectional survey in 2024 was conducted as part of a randomized controlled trial evaluating a well-being training among residents in high-burnout specialties (surgery, obstetrics-gynecology, family, internal, and emergency medicine). The survey assessed burnout and well-being outcomes. Prevalence rates of burnout or low well-being were calculated and compared across demographics. Regression models assessed associations with well-being, adjusting for demographic characteristics. 540 residents responded. The sample was predominantly cisgender women (67

Objective: Experiencing discrimination is associated with faster biological aging, as reflected in telomere shortening and DNA methylation. However, the impact of discrimination on brain aging processes remains unclear. Here, we tested whether individuals who reported at least one major lifetime discrimination event would exhibit steeper age-related associations in microstructural metrics within whole-brain white matter and the hippocampus, consistent with accelerated brain microstructural aging, compared with those with no such experiences. Methods: We analyzed multi-shell diffusion-weighted MRI data from the Midlife in the United States (MIDUS) cohort (n=147, mean age=65 years, range: 48 to 95 years) to assess brain microstructure using complementary statistical and biophysical diffusion models. Diffusion kurtosis imaging representation was used to derive diffusion tensor imaging (DTI) and white matter tract integrity (WMTI) measures. Additional microstructural health indices were derived using the neurite orientation dispersion and density imaging (NODDI) model. Permutation analyses of linear models were run within the whole-brain white matter and bilateral hippocampi, adjusting for sex, race, and education. Results: Participants who reported at least one major discriminatory experience during their lifetime exhibited accelerated age-associated changes in white matter microstructural measures, including higher mean and radial diffusivities, extra-axonal radial diffusivity, and free water fraction compared with those with no such experiences. Conclusions: These converging findings from complementary measures of brain microstructure suggest that major discrimination experiences may contribute to accelerated brain microstructural aging.

Reflections over the course of my 50-year career in interdisciplinary clinical-psychological science are offered. Using several examples drawn from my life’s work, I highlight the importance of interdisciplinarity in developing novel insights into clinically relevant phenomena. When questions demand expertise and methods beyond those researchers possess themselves, collaboration is key. Examples of highly novel and productive collaborations from my career are provided. Finally, I conclude with six specific points of advice for the younger generation of scientists, and I advocate for a clinical-psychological science that focuses on human flourishing. Such a focus is critically needed to address the major challenges facing the world today.

Objective: Studies investigating resting-state functional connectivity of the amygdala and hippocampus have produced inconsistent findings. The authors' objective was to conduct the largest systematic comparison of alterations in functional connectivity of the amygdala and hippocampus in individuals with posttraumatic stress disorder (PTSD) using a multicohort mega-analysis with uniform processing steps and parameters across all cohorts. Methods: Resting-state functional MRI data from 1,017 PTSD patients and 1,702 control participants from 32 international sites were centrally preprocessed with HALFpipe and analyzed using the Image-Based Meta- and Mega-Analysis (IBMMA) package for neuroimaging processing. Group-level seed-based whole-brain analyses were completed for the right and left amygdala and hippocampus. Additional correlation analyses were conducted between PTSD norm-severity scores and resting-state functional connectivity (rs-FC). Results: Compared to control participants, individuals with PTSD showed stronger rs-FC between the left amygdala seed and right hippocampus and amygdala and the left and right lingual gyri. Greater PTSD total norm-severity scores were significantly associated with rs-FC between the left amygdala and right hippocampus/amygdala and rs-FC between the right amygdala and left hippocampus/amygdala. Conclusions: Greater connectivity between subcortical threat centers involved in fear processing, memory, and extinction learning characterizes the resting state in PTSD. Future directions include investigating how different interventions, such as brain stimulation, neurofeedback, and psychotherapy, might modulate the aberrant neural networks in PTSD.

Mindfulness-based stress reduction (MBSR) can improve symptoms of chronic inflammation; in asthma, improving asthma control and reducing airway inflammation. Understanding the neural mechanisms underlying these salubrious outcomes could help identify neuroimmune phenotypes and personalize interventions. Adults with asthma were randomized to 8 weeks of MBSR (n = 38) or a wait-list group (n = 34). Clinically relevant asthma-related and psychological outcomes were measured, and task-based fMRI data were acquired during exposure to emotional cues at baseline, post-intervention, and 6mo follow-up. Whole-brain group x time interactions and voxelwise regressions were used to evaluate changes in neural responses to emotion cues from baseline and their relationship to psychological and biological outcomes. Post-intervention, MBSR participants showed decreased lateral prefrontal/orbitofrontal cortex responses to aversive cues relative to controls, which was associated with increased mindfulness. Across participants, decreased salience network reactivity at post-intervention was associated with reduced psychological distress and airway inflammation. At 6 months, some relationships persisted while others did not. Results suggest that mindfulness training reduced effortful regulation of cognitive and affective responses to emotional cues, instead promoting more efficient processing strategies and reduced affective reactivity. Our findings clarify neural mechanisms underlying MBSR's clinical benefits for asthma, underscoring mind-brain-immune relationships as a critical target for asthma treatment.

Importance:Burnout is highly prevalent among resident physicians, producing serious personal, professional, and system consequences. While work hour restrictions were implemented to improve patient safety and resident fatigue, the relationship between work hours with burnout and well-being remains unclear. Objective:To evaluate the association of work hours with burnout, stress, and self-perceived competency among residents in high-burnout specialties, and to explore potential demographic and well-being-related moderators. Design, Setting, and Participants:This cross-sectional study included responses from a remote survey conducted from February to June 2024 as part of a randomized clinical trial evaluating a well-being intervention among resident physicians. Eligible participants were residents enrolled in high-burnout specialty residency programs (surgery, obstetrics-gynecology, family, internal, and emergency medicine) in the US. Exposure:Self-reported average weekly work hours and total hours worked in the past week. Main Outcome and Measures:Burnout, stress, and self-assessed Accreditation Council for Graduate Medical Education (ACGME) competency milestones, adjusting for demographics. Results:A total of 540 residents responded (356 cisgender women [66.8%]; 112 Asian [21.1%], 28 Black [5.3%], 355 White [67.0%]). The sample was predominantly in a medical specialty (56%). The mean (SD) number of average hours worked was 65.4 (11.3) and the mean (SD) number of hours worked in the last week was 60.1 (17.4). There was no significant association between burnout and average hours worked (β = 0.05 [95% CI, -0.05 to 0.15]; P = .34) or hours worked last week (β = 0.06 [95% CI, -0.03 to 0.15]; P = .21). However, stress was positively associated with average hours worked (β = 0.17 [95% CI, 0.07 to 0.26]; P = .001) and hours worked last week (β = 0.27 [95% CI, 0.18 to 0.36]; P < .001). Self-assessed ACGME competency milestones were also positively associated with average hours worked (β = 0.14 [95% CI, 0.07 to 0.21]; P < .001) and hours worked last week (β = 0.08 [95% CI, 0.01 to 0.15]; P = .02). Despite exploring a large set of candidate moderators, very few moderators were identified and none survived P value adjustment. Conclusion and Relevance:In this cross-sectional nationwide study of resident physicians in high-burnout specialties, longer work hours were associated with higher stress and self-perceived competency, but not with burnout. This suggests that work hours alone may not explain high burnout levels in residency; a more comprehensive approach beyond work hour restrictions is needed to support resident well-being in training.

BACKGROUND:Slow waves are oscillations that reflect rhythmic alternation of neuronal activity and mediate key restorative functions of non-rapid eye movement (NREM) sleep. Left ventromedial prefrontal cortex regions are a "hot spot" for slow wave generation. The enhancement of slow wave activity (SWA, 0.5-4 Hz) has been shown to be beneficial, as in improving memory performance. To overcome limitations of current techniques, we assessed the ability of a non-invasive neuromodulatory tool, Transcranial Electrical Stimulation with Temporal Interference (TES-TI), to enhance SWA during NREM sleep overnight in healthy humans. METHODS:The current study is an interim analysis focused on the effects of TES-TI during NREM sleep in a laboratory setting. Two high frequency carriers with 1 Hz difference (TES15kHz-TI1Hz) produced amplitude-modulated temporal interference at 1Hz. Data were collected at the University of Wisconsin-Madison as part of the STRENGTHEN study (ClinicalTrials.gov, NCT06267521, 02/12/2024, single-blind, non-random allocation). Eligible participants were healthy adults (ages 18-50) assigned in parallel to one of four groups: (Group 1) TES15kHz (0 Hz difference frequency) 2 nights per week and meditation; (Group 2) TES15kHz-TI1Hz (1 Hz difference frequency) 2 nights per week and sham meditation; (Group 3) TES15kHz-TI1Hz 1 night per week and meditation; (Group 4) TES15kHz-TI1Hz 2 nights per week and meditation. Stimulation targeting left ventromedial prefrontal cortex occurred during NREM sleep over repeated nights ( ~ 10 stimulation periods, 3-min each, first half of night, 1-2 nights/week, 4-week protocol). Twenty-one participants (Groups 2, 3, 4) received TES15kHz-TI1Hz and seven participants received TES15kHz (Group 1). SWA was measured using simultaneous high-density electroencephalography with polysomnography. RESULTS:We show that SWA is increased with TES15kHz-TI1Hz (N = 21 total; N = 5 Group 2, N = 10 Group 3, N = 6 Group 4), and the effect outlasts the stimulation period; higher frequencies (sigma and beta) decrease. During stimulation, SWA is greater in TES15kHz-TI1Hz than pure TES15kHz (N = 7 Group 1). The incremental effects of TES15kHz-TI1Hz on SWA between first and last intervention night are positively associated with subjective ratings of restorative sleep. CONCLUSIONS:To our knowledge, this is the first study demonstrating that TES-TI enhances SWA and potentially its restorative function.

Digital technology opens the possibility of providing meditation instruction in the midst of daily activities. This study explores the use of “active” meditation practices which involve meditating while completing daily activities (e.g., folding laundry). We used data from public users of the Healthy Minds Program (HMP) meditation app (N = 26,532, Sample 1) and from a recently completed trial testing the HMP app (N = 248, Sample 2). We examined associations between the proportion of practices completed as active practices (Active Proportion) with participant demographics, baseline psychological distress, patterns of app utilization, and changes in psychological distress. Although sitting practice was used more commonly than active practices, active practices were frequently used (38 https://clinicaltrials.gov/ct2/show/NCT04426318 ). All analyses reported here were not preregistered.

Low economic status is linked to poorer mental and physical well-being, but individual differences in emotional and cognitive resources may buffer this relationship. Indeed, previous research has shown that people with low income but a high sense of control have comparable levels of life satisfaction and health to people with higher income. Building on this, we conducted two cross-sectional online studies with US participants to examine whether healthy emotionality-a predisposition to adaptive affective responses-buffers the negative effects of low economic status on well-being. In Study 1 (N = 259), participants completed the Emotional Style Questionnaire, rated their life satisfaction and health, and reported annual household income. In Study 2 (N = 902), we used more comprehensive assessments of income and well-being, and additionally compared the moderating effects of healthy emotionality and sense of control. In both studies, healthy emotionality significantly moderated the relationship between income and well-being: individuals with high healthy emotionality maintained higher well-being despite low economic status. This buffering effect remained significant when the sense of control was included in the model. These results suggest that healthy emotionality is a robust resilience factor against socioeconomic adversity that goes beyond the protective role of perceived control.