Connectome predictive modeling of trait mindfulness.

Introduction: Trait mindfulness refers to one's disposition or tendency to pay attention to their experiences in the present moment, in a non-judgmental and accepting way. Trait mindfulness has been robustly associated with positive mental health outcomes, but its neural underpinnings are poorly understood. Prior resting-state fMRI studies have associated trait mindfulness with within- and between-network connectivity of the default-mode (DMN), fronto-parietal (FPN), and salience networks. However, it is unclear how generalizable the findings are, how they relate to different components of trait mindfulness, and how other networks and brain areas may be involved. Methods: To address these gaps, we conducted the largest resting-state fMRI study of trait mindfulness to-date, consisting of a pre-registered connectome predictive modeling analysis in 367 adults across three samples collected at different sites. Results: In the model-training dataset, we did not find connections that predicted overall trait mindfulness, but we identified neural models of two mindfulness subscales, Acting with Awareness and Non-judging. Models included both positive networks (sets of pairwise connections that positively predicted mindfulness with increasing connectivity) and negative networks, which showed the inverse relationship. The Acting with Awareness and Non-judging positive network models showed distinct network representations involving FPN and DMN, respectively. The negative network models, which overlapped significantly across subscales, involved connections across the whole brain with prominent involvement of somatomotor, visual and DMN networks. Only the negative networks generalized to predict subscale scores out-of-sample, and not across both test datasets. Predictions from both models were also negatively correlated with predictions from a well-established mind-wandering connectome model. Conclusions: We present preliminary neural evidence for a generalizable connectivity models of trait mindfulness based on specific affective and cognitive facets. However, the incomplete generalization of the models across all sites and scanners, limited stability of the models, as well as the substantial overlap between the models, underscores the difficulty of finding robust brain markers of mindfulness facets.

Healthy Minds Index: A brief measure of the core dimensions of well-being.

We developed a self-report measure of psychological well-being for teens and adults, the Healthy Minds Index, based on a novel theory that four trainable pillars underlie well-being: awareness, connection, insight, and purpose. Ninety-seven items were developed and revised by experts and guided by qualitative testing with teens (n = 32; average age = 16.0 years). After assessing the internal validity and factor structure in teens (n = 1607; average age = 16.7 years) and adults (n = 420; average age = 45.6 years), we reduced the survey to 17 items. We then validated the factor structure, internal and convergent and divergent validity, and retest reliability of the 17-item Healthy Minds Index in two new teen samples (study 1: n = 1492, average age = 15.7 years; study 2: n = 295, average age = 16.1 years), and one adult sample (n = 285; average age = 45.3 years). The Healthy Minds Index demonstrated adequate validity and provided a comprehensive measure of a novel theory of psychological well-being that includes two domains not found in other conceptualizations of this construct-awareness and insight. This measure will be invaluable for primary research on well-being and as a translational tool to assess the impact and efficacy of widely used behavioral training programs on these core dimensions of wellbeing.

Resting state functional connectivity changes following mindfulness-based stress reduction predict improvements in disease control for patients with asthma.

BACKGROUND: The staggering morbidity associated with chronic inflammatory diseases can be reduced by psychological interventions, including Mindfulness-Based Stress Reduction (MBSR). Proposed mechanisms for MBSR's beneficial effects include changes in salience network function. Salience network perturbations are also associated with chronic inflammation, including airway inflammation in asthma, a chronic inflammatory disease affecting approximately 10% of the population. However, no studies have examined whether MBSR-related improvements in disease control are related to changes in salience network function. METHODS: Adults with asthma were randomized to 8 weeks of MBSR or a waitlist control group. Resting state functional connectivity was measured using fMRI before randomization, immediately post-intervention, and 4 months post-intervention. Using key salience network regions as seeds, we calculated group differences in change in functional connectivity over time and examined whether functional connectivity changes were associated with increased mindfulness, improved asthma control, and decreased inflammatory biomarkers. RESULTS: The MBSR group showed greater increases in functional connectivity between salience network regions relative to the waitlist group. Improvements in asthma control correlated with increased functional connectivity between the salience network and regions important for attention control and emotion regulation. Improvements in inflammatory biomarkers were related to decreased functional connectivity between the salience network and other networks. CONCLUSIONS: Increased resting salience network coherence and connectivity with networks that subserve attention and emotion regulation may contribute to the benefits of MBSR for patients with asthma. Understanding the neural underpinnings of MBSR-related benefits in patients is a critical step towards optimizing brain-targeted interventions for chronic inflammatory disease management.

Slower respiration rate is associated with higher self-reported well-being after wellness training.

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.

Neural Signatures of Pain Modulation in Short-Term and Long-Term Mindfulness Training: A Randomized Active-Control Trial.

OBJECTIVE: Mindfulness-based interventions are widely used to target pain, yet their neural mechanisms of action are insufficiently understood. The authors studied neural and subjective pain response in a randomized active-control trial of mindfulness-based stress reduction (MBSR) alongside long-term meditation practitioners. METHODS: Healthy participants (N=115) underwent functional neuroimaging during a thermal acute pain task before and after random assignment to MBSR (N=28), an active control condition (health enhancement program [HEP]) (N=32), or a waiting list control condition (N=31). Long-term meditators (N=30) completed the same neuroimaging paradigm. Pain response was measured via self-reported intensity and unpleasantness, and neurally via two multivoxel machine-learning-derived signatures: the neurologic pain signature (NPS), emphasizing nociceptive pain processing, and the stimulus intensity independent pain signature-1 (SIIPS1), emphasizing stimulus-independent neuromodulatory processes. RESULTS: The MBSR group showed a significant decrease in NPS response relative to the HEP group (Cohen's d=-0.43) and from pre- to postintervention assessment (d=-0.47). The MBSR group showed small, marginal decreases in NPS relative to the waiting list group (d=-0.36), and in SIIPS1 relative to both groups (HEP group, d=-0.37; waiting list group, d=-0.37). In subjective unpleasantness, the MBSR and HEP groups also showed modest significant reductions compared with the waiting list group (d=-0.45 and d=-0.55). Long-term meditators reported significantly lower pain than nonmeditators but did not differ in neural response. Within the long-term meditator group, cumulative practice during intensive retreat was significantly associated with reduced SIIPS1 (r=-0.65), whereas daily practice was not. CONCLUSIONS: Mindfulness training showed associations with pain reduction that implicate differing neural pathways depending on extent and context of practice. Use of neural pain signatures in randomized trials offers promise for guiding the application of mindfulness interventions to pain treatment.

Long-term Meditation Training Is Associated with Enhanced Subjective Attention and Stronger Posterior Cingulate-Rostrolateral Prefrontal Cortex Resting Connectivity.

Mindfulness meditation has been shown to increase resting-state functional connectivity (rsFC) between the posterior cingulate cortex (PCC) and dorsolateral prefrontal cortex (DLPFC), which is thought to reflect improvements in shifting attention to the present moment. However, prior research in long-term meditation practitioners lacked quantitative measures of attention that would provide a more direct behavioral correlate and interpretational anchor for PCC-DLPFC connectivity and was inherently limited by small sample sizes. Moreover, whether mindfulness meditation primarily impacts brain function locally, or impacts the dynamics of large-scale brain networks, remained unclear. Here, we sought to replicate and extend prior findings of increased PCC-DLPFC rsFC in a sample of 40 long-term meditators (average practice = 3759 hr) who also completed a behavioral assay of attention. In addition, we tested a network-based framework of changes in interregional connectivity by examining network-level connectivity. We found that meditators had stronger PCC-rostrolateral prefrontal cortex (RLPFC) rsFC, lower connector hub strength across the default mode network, and better subjective attention, compared with 124 meditation-naive controls. Orienting attention positively correlated with PCC-RLPFC connectivity and negatively correlated with default mode network connector hub strength. These findings provide novel evidence that PCC-RLPFC rsFC may support attention orienting, consistent with a role for RLPFC in the attention shifting component of metacognitive awareness that is a core component of mindfulness meditation training. Our results further demonstrate that long-term mindfulness meditation may improve attention and strengthen the underlying brain networks.

Absence of structural brain changes from mindfulness-based stress reduction: Two combined randomized controlled trials.

Studies purporting to show changes in brain structure following the popular, 8-week mindfulness-based stress reduction (MBSR) course are widely referenced despite major methodological limitations. Here, we present findings from a large, combined dataset of two, three-arm randomized controlled trials with active and waitlist (WL) control groups. Meditation-naïve participants (n = 218) completed structural magnetic resonance imaging scans during two visits: baseline and postintervention period. After baseline, participants were randomly assigned to WL (n = 70), an 8-week MBSR program (n = 75), or a validated, matched active control (n = 73). We assessed changes in gray matter volume, gray matter density, and cortical thickness. In the largest and most rigorously controlled study to date, we failed to replicate prior findings and found no evidence that MBSR produced neuroplastic changes compared to either control group, either at the whole-brain level or in regions of interest drawn from prior MBSR studies.

DIVERSITY OF SIDEROPHORE-PRODUCING BACTERIAL CULTURES FROM CARLSBAD CAVERNS NATIONAL PARK (CCNP) CAVES, CARLSBAD, NEW MEXICO.

Siderophores are microbially-produced ferric iron chelators. They are essential for microbial survival, but their presence and function for cave microorganisms have not been extensively studied. Cave environments are nutrient-limited and previous evidence suggests siderophore usage in carbonate caves. We hypothesize that siderophores are likely used as a mechanism in caves to obtain critical nutrients such as iron. Cave bacteria were collected from Long-term parent cultures (LT PC) or Short-term parent cultures (ST PC) inoculated with ferromanganese deposits (FMD) and carbonate secondary minerals from Lechuguilla and Spider caves in Carlsbad Caverns National Park (CCNP), NM. LT PC were incubated for 10-11 years to identify potential chemolithoheterotrophic cultures able to survive in nutrient-limited conditions. ST PC were incubated for 1-3 days to identify a broader diversity of cave isolates. A total of 170 LT and ST cultures,18 pure and 152 mixed, were collected and used to classify siderophore production and type and to identify siderophore producers. Siderophore production was slow to develop (>10 days) in LT cultures with a greater number of weak siderophore producers in comparison to the ST cultures that produced siderophores in <10 days, with a majority of strong siderophore producers. Overall, 64% of the total cultures were siderophore producers, which the majority preferred hydroxamate siderophores. Siderophore producers were classified into Proteobacteria (Alpha-, Beta-, or Gamma-), Actinobacteria, Bacteroidetes, and Firmicutes phyla using 16S rRNA gene sequencing. Our study supports our hypothesis that cave bacteria have the capability to produce siderophores in the subsurface to obtain critical ferric iron.

The calcium-activated chloride channel-associated protein rCLCA2 is expressed throughout rat epidermis, facilitates apoptosis and is downmodulated by UVB.

The rodent chloride channel regulatory proteins mCLCA2 and its porcine and human homologues pCLCA2 and hCLCA2 are expressed in keratinocytes but their localization and significance in the epidermis have remained elusive. hCLCA2 regulates cancer cell migration, invasion and apoptosis, and its loss predicts poor prognosis in many tumors. Here, we studied the influences of epidermal maturation and UV-irradiation (UVR) on rCLCA2 (previous rCLCA5) expression in cultured rat epidermal keratinocytes (REK) and correlated the results with mCLCA2 expression in mouse skin in vivo. Furthermore, we explored the influence of rCLCA2 silencing on UVR-induced apoptosis. rClca2 mRNA was strongly expressed in REK cells, and its level in organotypic cultures remained unchanged during the epidermal maturation process from a single cell layer to fully differentiated, stratified cultures. Immunostaining confirmed its uniform localization throughout the epidermal layers in REK cultures and in rat skin. A single dose of UVR modestly downregulated rClca2 expression in organotypic REK cultures. The immunohistochemical staining showed that CLCA2 localized in basal and spinous layers also in mouse skin, and repeated UVR induced its partial loss. Interestingly, silencing of rCLCA2 reduced the number of apoptotic cells induced by UVR, suggesting that by facilitating apoptosis, CLCA2 may protect keratinocytes against the risk of malignancy posed by UVB-induced corrupt DNA.

Differential response of human T-lymphocytes to arsenic and uranium.

Elevated levels of arsenic and uranium have been detected in water sources near abandoned uranium mines in the Southwest. Evidence suggests uranium exposure increases the likelihood of immune dysfunction and this study investigates the impact of arsenic and uranium on human immune cell lines. Concentration-dependent cytotoxicity occurred following exposure to arsenite, whereas cells remained viable after 48 -h treatment with up to 100 µM uranyl acetate despite uptake of uranium into cells. Arsenite stimulated an oxidative stress response as detected by Nrf-2 nuclear accumulation and induction of HMOX-1 and NQO1, which was not detected with up to 30 µM uranyl acetate. Cellular oxidative stress can promote DNA damage and arsenite, but not uranium, stimulated DNA damage as measured by pH2AX. Arsenic enhanced the cytotoxic response to etoposide suggesting an inhibition of DNA repair, unlike uranium. Similarly, uranium did not inhibit PARP-1 activity. Because uranium reportedly stimulates oxidative stress, DNA damage and cytotoxicity in adherent epithelial cells, the current study suggests distinct cell type differences in response to uranium that may relate to generation of oxidative stress and associated downstream consequences. Delineating the actions of uranium across different cell targets will be important for understanding the potential health effects of uranium exposures.

Mindfulness video game improves connectivity of the fronto-parietal attentional network in adolescents: A multi-modal imaging study.

Mindfulness training has been shown to improve attention and change the underlying brain substrates in adults. Most mindfulness training programs involve a myriad of techniques, and it is difficult to attribute changes to any particular aspect of the program. Here, we created a video game, Tenacity, which models a specific mindfulness technique - focused attention on one's breathing - and assessed its potential to train an attentional network in adolescents. A combined analysis of resting state functional connectivity (rs-FC) and diffusion tensor imaging (DTI) yielded convergent results - change in communication within the left fronto-parietal network after two weeks of playing Tenacity compared to a control game. Rs-FC analysis showed greater connectivity between left dorsolateral prefrontal cortex (dlPFC) and left inferior parietal cortex (IPC) in the Tenacity group. Importantly, changes in left dlPFC - IPC rs-FC and changes in structural connectivity of the white matter tract that connects these regions -left superior longitudinal fasiculus (SLF) - were associated with changes in performance on an attention task. Finally, changes in left dlPFC - IPC rs-FC correlated with the change in left SLF structural connectivity as measured by fractional anisotropy (FA) in the Tenacity group only.

The Effect of Mindfulness Meditation on Impulsivity and its Neurobiological Correlates in Healthy Adults.

Interest has grown in using mindfulness meditation to treat conditions featuring excessive impulsivity. However, while prior studies find that mindfulness practice can improve attention, it remains unclear whether it improves other cognitive faculties whose deficiency can contribute to impulsivity. Here, an eight-week mindfulness intervention did not reduce impulsivity on the go/no-go task or Barratt Impulsiveness Scale (BIS-11), nor produce changes in neural correlates of impulsivity (i.e. frontostriatal gray matter, functional connectivity, and dopamine levels) compared to active or wait-list control groups. Separately, long-term meditators (LTMs) did not perform differently than meditation-naïve participants (MNPs) on the go/no-go task. However, LTMs self-reported lower attentional impulsivity, but higher motor and non-planning impulsivity on the BIS-11 than MNPs. LTMs had less striatal gray matter, greater cortico-striatal-thalamic functional connectivity, and lower spontaneous eye-blink rate (a physiological dopamine indicator) than MNPs. LTM total lifetime practice hours (TLPH) did not significantly relate to impulsivity or neurobiological metrics. Findings suggest that neither short- nor long-term mindfulness practice may be effective for redressing impulsive behavior derived from inhibitory motor control or planning capacity deficits in healthy adults. Given the absence of TLPH relationships to impulsivity or neurobiological metrics, differences between LTMs and MNPs may be attributable to pre-existing differences.

Mindfulness-Based Stress Reduction-related changes in posterior cingulate resting brain connectivity.

Mindfulness meditation training has been shown to increase resting-state functional connectivity between nodes of the frontoparietal executive control network (dorsolateral prefrontal cortex [DLPFC]) and the default mode network (posterior cingulate cortex [PCC]). We investigated whether these effects generalized to a Mindfulness-Based Stress Reduction (MBSR) course and tested for structural and behaviorally relevant consequences of change in connectivity. Healthy, meditation-naïve adults were randomized to either MBSR (N = 48), an active (N = 47) or waitlist (N = 45) control group. Participants completed behavioral testing, resting-state fMRI scans and diffusion tensor scans at pre-randomization (T1), post-intervention (T2) and ~5.5 months later (T3). We found increased T2-T1 PCC-DLPFC resting connectivity for MBSR relative to control groups. Although these effects did not persist through long-term follow-up (T3-T1), MBSR participants showed a significantly stronger relationship between days of practice (T1 to T3) and increased PCC-DLPFC resting connectivity than participants in the active control group. Increased PCC-DLPFC resting connectivity in MBSR participants was associated with increased microstructural connectivity of a white matter tract connecting these regions and increased self-reported attention. These data show that MBSR increases PCC-DLPFC resting connectivity, which is related to increased practice time, attention and structural connectivity.

Mindfulness Meditation and Psychopathology.

Mindfulness meditation is increasingly incorporated into mental health interventions, and theoretical concepts associated with it have influenced basic research on psychopathology. Here, we review the current understanding of mindfulness meditation through the lens of clinical neuroscience, outlining the core capacities targeted by mindfulness meditation and mapping them onto cognitive and affective constructs of the Research Domain Criteria matrix proposed by the National Institute of Mental Health. We review efficacious applications of mindfulness meditation to specific domains of psychopathology including depression, anxiety, chronic pain, and substance abuse, as well as emerging efforts related to attention disorders, traumatic stress, dysregulated eating, and serious mental illness. Priorities for future research include pinpointing mechanisms, refining methodology, and improving implementation. Mindfulness meditation is a promising basis for interventions, with particular potential relevance to psychiatric comorbidity. The successes and challenges of mindfulness meditation research are instructive for broader interactions between contemplative traditions and clinical psychological science.

Increased BNST reactivity to affective images is associated with greater α-amylase response to social stress.

While rodent research suggests that the bed nucleus of the stria terminalis (BNST) and centromedial amygdala (CM) coordinate the hormonal stress response, little is known about the BNST's role in the human stress response. The human BNST responds to negatively valenced stimuli, which likely subserves its role in responding to threat. Thus, variation in BNST reactivity to negatively valenced stimuli may relate to differences in the stress response. We measured participants' blood oxygenated level-dependent response to affective images and salivary cortisol and α-amylase (AA) levels in response to a subsequent Trier social stress test (TSST). Greater BNST activation to emotionally evocative images was associated with a larger TSST-evoked AA, but not cortisol response. This association remained after controlling for CM activation, which was not related to the cortisol or AA response. These results suggest that the BNST response to negatively valenced images subserves its role in coordinating the stress response, a BNST role in the stress response independent from the CM, and highlight the need for investigation of the conditions under which BNST activation predicts the cortisol response. Our findings are critical for the future study of mood and anxiety disorders, as dysregulation of the stress system plays a key role in their pathogenesis.

Impact of short- and long-term mindfulness meditation training on amygdala reactivity to emotional stimuli.

Meditation training can improve mood and emotion regulation, yet the neural mechanisms of these affective changes have yet to be fully elucidated. We evaluated the impact of long- and short-term mindfulness meditation training on the amygdala response to emotional pictures in a healthy, non-clinical population of adults using blood-oxygen level dependent functional magnetic resonance imaging. Long-term meditators (N = 30, 16 female) had 9081 h of lifetime practice on average, primarily in mindfulness meditation. Short-term training consisted of an 8-week Mindfulness- Based Stress Reduction course (N = 32, 22 female), which was compared to an active control condition (N = 35, 19 female) in a randomized controlled trial. Meditation training was associated with less amygdala reactivity to positive pictures relative to controls, but there were no group differences in response to negative pictures. Reductions in reactivity to negative stimuli may require more practice experience or concentrated practice, as hours of retreat practice in long-term meditators was associated with lower amygdala reactivity to negative pictures - yet we did not see this relationship for practice time with MBSR. Short-term training, compared to the control intervention, also led to increased functional connectivity between the amygdala and a region implicated in emotion regulation - ventromedial prefrontal cortex (VMPFC) - during affective pictures. Thus, meditation training may improve affective responding through reduced amygdala reactivity, and heightened amygdala-VMPFC connectivity during affective stimuli may reflect a potential mechanism by which MBSR exerts salutary effects on emotion regulation ability.

Hyaluronan metabolism enhanced during epidermal differentiation is suppressed by vitamin C.

BACKGROUND: Hyaluronan is a large, linear glycosaminoglycan present throughout the narrow extracellular space of the vital epidermis. Increased hyaluronan metabolism takes place in epidermal hypertrophy, wound healing and cancer. Hyaluronan is produced by hyaluronan synthases and catabolized by hyaluronidases, reactive oxygen species and KIAA1199. OBJECTIVES: To investigate the changes in hyaluronan metabolism during epidermal stratification and maturation, and the impact of vitamin C on these events. METHODS: Hyaluronan synthesis and expression of the hyaluronan-related genes were analysed during epidermal maturation from a simple epithelium to a fully differentiated epidermis in organotypic cultures of rat epidermal keratinocytes using quantitative reverse transcriptase polymerase chain reaction, immunostaining and Western blotting, in the presence and absence of vitamin C. RESULTS: With epidermal stratification, both the production and the degradation of hyaluronan were enhanced, resulting in an increase of hyaluronan fragments of various sizes. While the mRNA levels of Has3 and KIAA1199 remained stable during the maturation, Has1, Has2 and Hyal2 showed a transient upregulation during stratification, Hyal1 transcription remained permanently increased and transcription of the hyaluronan receptor, Cd44, decreased. At maturation, vitamin C downregulated Has2, Hyal2 and Cd44, whereas it increased high-molecular-mass hyaluronan in the epidermis, and reduced small fragments in the medium, suggesting stabilization of epidermal hyaluronan. CONCLUSIONS: Epidermal stratification and maturation is associated with enhanced hyaluronan turnover, and release of large amounts of hyaluronan fragments. The high turnover is suppressed by vitamin C, which is suggested to enhance normal epidermal differentiation in part through its effect on hyaluronan.

Neural correlates of video game empathy training in adolescents: a randomized trial.

The ability to understand emotional experiences of others, empathy, is a valuable skill for effective social interactions. Various types of training increase empathy in adolescents, but their impact on brain circuits underlying empathy has not been examined. Video games provide a unique medium familiar and engaging to adolescents and can be used to deliver training at scale. We developed an empathy training video game, Crystals of Kaydor (Crystals), and investigated whether playing Crystals increases empathic accuracy (EA) and related brain activation in adolescents (N = 74; 27 female; mean age(sd) = 12.8(0.7) years; age range 11-14 years). Participants completed a resting state functional MRI (rs-fMRI) scan and an EA task during an fMRI scan before and after 2 weeks of daily gameplay with either the empathy training game, Crystals (N = 34), or the commercial video game Bastion (N = 40), an active control condition. There were no group differences in EA improvement following gameplay, however, engagement with training aspects of Crystals was associated with a higher increase in EA-related activation in right temporoparietal junction following gameplay. Moreover, rs-fMRI connectivity in empathy-related brain circuits (posterior cingulate-medial prefrontal cortex; MPFC) was stronger after Crystals gameplay compared to Bastion. The more individuals' EA increased following Crystals versus Bastion, the stronger their rs-fMRI connectivity in brain circuits relevant for emotion regulation (amygdala-MPFC). These findings suggest that a video game designed to increase empathic accuracy produces behaviorally-relevant, functional neural changes in fewer than 6 h of gameplay in adolescents.

Papillary Thyroid Carcinoma (PTC) in Children and Adults: Comparison of Initial Presentation and Long-Term Postoperative Outcome in 4432 Patients Consecutively Treated at the Mayo Clinic During Eight Decades (1936-2015).

BACKGROUND: Contemporary guidelines for managing PTC advise an approach wherein primary tumor and regional metastases (RM) are completely resected at first surgery and radioiodine remnant ablation (RRA) is restricted to high-risk patients, policies our group has long endorsed. To assess our therapeutic efficacy, we studied 190 children and 4242 adults consecutively treated during 1936-2015. SUBJECTS AND METHODS: Mean follow-up durations for children and adults were 26.9 and 15.2 years, respectively. Bilateral lobar resection was performed in 86% of children and 88% of adults, followed by RRA in 30% of children and 29% of adults; neck nodes were excised in 86% of children and 66% of adults. Tumor recurrence (TR) and cause-specific mortality (CSM) details were taken from a computerized database. RESULTS: Children, when compared to adults, had larger primary tumors which more often were grossly invasive and incompletely resected. At presentation, children, as compared to adults, had more RM and distant metastases (DM). Thirty-year TR rates were no different in children than adults at any site. Thirty-year CSM rates were lower in children than adults (1.1 vs. 4.9%; p = 0.01). Comparing 1936-1975 (THEN) with 1976-2015 (NOW), 30-year CSM rates were similar in MACIS <6 children (p = 0.67) and adults (p = 0.08). However, MACIS <6 children and adults in 1976-2015 had significantly higher recurrence at local and regional, but not at distant, sites. MACIS 6+ adults, NOW, compared to THEN, had lower 30-year CSM rates (30 vs. 47%; p < 0.001), unassociated with decreased TR at any site. CONCLUSIONS: Children, despite presenting with more extensive PTC when compared to adults, have postoperative recurrences at similar frequency, typically coexist with DM and die of PTC less often. Since 1976, both children and adults with MACIS <6 PTC have a <1% chance at 30 years of CSM; adults with higher MACIS scores (6 or more) have a 30-year CSM rate of 30%.