Association between arterial oxygen and mortality across critically ill patients with hematologic malignancies: results from an international collaborative network.

PURPOSE: Patients with hematological malignancies are at high risk for life-threatening complications. To date, little attention has been paid to the impact of hyperoxemia and excess oxygen use on mortality. The aim of this study was to investigate the association between partial pressure of arterial oxygen (PaO2) and 28-day mortality in critically ill patients with hematologic malignancies. METHODS: Data from three international cohorts (Europe, Canada, Oceania) of patients who received respiratory support (noninvasive ventilation, high-flow nasal cannula, invasive mechanical ventilation) were obtained. We used mixed-effect Cox models to investigate the association between day one PaO2 or excess oxygen use (inspired fraction of oxygen ≥ 0.6 with PaO2 > 100 mmHg) on day-28 mortality. RESULTS: 11,249 patients were included. On day one, 5716 patients (50.8%) had normoxemia (60 ≤ PaO2 ≤ 100 mmHg), 1454 (12.9%) hypoxemia (PaO2 < 60 mmHg), and 4079 patients (36.3%) hyperoxemia (PaO2 > 100 mmHg). Excess oxygen was used in 2201 patients (20%). Crude day-28 mortality rate was 40.6%. There was a significant association between PaO2 and day-28 mortality with a U-shaped relationship (p < 0.001). Higher PaO2 levels (> 100 mmHg) were associated with day-28 mortality with a dose-effect relationship. Subgroup analyses showed an association between hyperoxemia and mortality in patients admitted with neurological disorders; however, the opposite relationship was seen across those admitted with sepsis and neutropenia. Excess oxygen use was also associated with subsequent day-28 mortality (adjusted hazard ratio (aHR) [95% confidence interval (CI)]: 1.11[1.04-1.19]). This result persisted after propensity score analysis (matched HR associated with excess oxygen:1.31 [1.20-1.1.44]). CONCLUSION: In critically-ill patients with hematological malignancies, exposure to hyperoxemia and excess oxygen use were associated with increased mortality, with variable magnitude across subgroups. This might be a modifiable factor to improve mortality.

Sources of richness and ineffability for phenomenally conscious states.

Conscious states-state that there is something it is like to be in-seem both rich or full of detail and ineffable or hard to fully describe or recall. The problem of ineffability, in particular, is a longstanding issue in philosophy that partly motivates the explanatory gap: the belief that consciousness cannot be reduced to underlying physical processes. Here, we provide an information theoretic dynamical systems perspective on the richness and ineffability of consciousness. In our framework, the richness of conscious experience corresponds to the amount of information in a conscious state and ineffability corresponds to the amount of information lost at different stages of processing. We describe how attractor dynamics in working memory would induce impoverished recollections of our original experiences, how the discrete symbolic nature of language is insufficient for describing the rich and high-dimensional structure of experiences, and how similarity in the cognitive function of two individuals relates to improved communicability of their experiences to each other. While our model may not settle all questions relating to the explanatory gap, it makes progress toward a fully physicalist explanation of the richness and ineffability of conscious experience-two important aspects that seem to be part of what makes qualitative character so puzzling.

Long-term survival and functional outcomes of critically ill patients with hematologic malignancies: a Canadian multicenter prospective study.

PURPOSE: Patients with hematologic malignancy (HM) commonly develop critical illness. Their long-term survival and functional outcomes have not been well described. METHODS: We conducted a prospective, observational study of HM patients admitted to seven Canadian intensive care units (ICUs) (2018-2020). We followed survivors at 7 days, 6 months and 12 months following ICU discharge. The primary outcome was 12-month survival. We evaluated functional outcomes at 6 and 12 months using the functional independent measure (FIM) and short form (SF)-36 as well as variables associated with 12-month survival. RESULTS: We enrolled 414 patients including 35% women. The median age was 61 (interquartile range, IQR: 52-69), median Sequential Organ Failure Assessment (SOFA) score was 9 (IQR: 6-12), and 22% had moderate-severe frailty (clinical frailty scale [CFS] ≥ 6). 51% had acute leukemia, 38% lymphoma/multiple myeloma, and 40% had received a hematopoietic stem cell transplant (HCT). The most common reasons for ICU admission were acute respiratory failure (50%) and sepsis (40%). Overall, 203 (49%) were alive 7 days post-ICU discharge (ICU survivors). Twelve-month survival of the entire cohort was 21% (43% across ICU survivors). The proportion of survivors with moderate-severe frailty was 42% (at 7 days), 14% (6 months), and 8% (12 months). Median FIM at 7 days was 80 (IQR: 50-109). Physical function, pain, social function, mental health, and emotional well-being were below age- and sex-matched population scores at 6 and 12 months. Frailty, allogeneic HCT, kidney injury, and cardiac complications during ICU were associated with lower 12- month survival. CONCLUSIONS: 49% of all HM patients were alive at 7 days post-ICU discharge, and 21% at 12 months. Survival varied based upon hematologic diagnosis and frailty status. Survivors had important functional disability and impairment in emotional, physical, and general well-being.

Corticosteroids induce an early but limited decrease in IL-6 dependent pro-inflammatory responses in critically ill COVID-19 patients.

BACKGROUND: Corticosteroids have become standard of care for COVID-19 but their effect on the systemic immune-inflammatory response has been little investigated. METHODS: Multicenter prospective cohort, including critically ill COVID-19 patients between March and November 2020. C-reactive protein (CRP), lymphocyte count and fibrinogen levels were collected upon hospital admission before initiation of steroid treatment and at ICU admission, three days and seven days later, along with interleukin (IL)-6, IL-10 and tumor necrosis factor-alpha (TNF-α) plasma levels. RESULTS: A hundred and fifty patients were included, 47 received corticosteroids, 103 did not. Median age was 62 [53-70], and 96 (65%) patients were mechanically ventilated. Propensity score matching rendered 45 well-balanced pairs of treated and non-treated patients, particularly on pre-treatment CRP levels. Using a mixed model, CRP (P=0.019), fibrinogen (P=0.003) and lymphocyte counts (P=0.006) remained lower in treated patients over ICU stay. Conversely, there was no significant difference over the ICU stay for Il-6 (P=0.146) and IL-10 (0.301), while TNF- α levels were higher in the treated group (P=0.013). Among corticosteroid-treated patients, CRP (P=0.012), fibrinogen (P=0.041) and lymphocyte count (P=0.004) over time were associated with outcome, whereas plasma cytokine levels were not. CONCLUSIONS: Steroid treatment was associated with an early and sustained decrease in the downstream IL-6-dependent inflammatory signature but an increase in TNF-α levels. In corticosteroid-treated patients, CRP and lymphocyte count were associated with outcome, conversely to plasma cytokine levels. Further research on using these biomarker's kinetics to individualize immunomodulatory treatments is warranted.

Resilience and Mental-Health Symptoms in ICU Healthcare Professionals Facing Repeated COVID-19 Waves.

Rationale: Psychological resilience (the ability to thrive in adversity) may protect against mental-health symptoms in healthcare professionals during coronavirus disease (COVID-19) waves. Objectives: To identify determinants of resilience in ICU staff members. Methods: In this cross-sectional survey in 21 French ICUs, staff members completed the 10-item Connor-Davidson Resilience Scale, Hospital Anxiety and Depression Scale, and Impact of Event Scale-Revised (for post-traumatic stress disorder [PTSD]). Factors independently associated with resilience were identified. Measurements and Main Results: The response rate was 73.1% (950 of 1,300). The median 10-item Connor-Davidson Resilience Scale score was 29 (interquartile range, 25-32). Symptoms of anxiety, depression, and PTSD were present in 61%, 39%, and 36% of staff members, respectively. Distress associated with the COVID-19 infodemic was correlated with symptoms of depression and PTSD. More resilient respondents less often had symptoms of anxiety, depression, and PTSD. Greater resilience was independently associated with male sex, having provided intensive care during the early waves, having managed more than 50 patients with COVID-19, and, compared with earlier waves, working longer hours, having greater motivation, and more often involving families in end-of-life decisions. Independent risk factors for lower resilience were having managed more than 10 patients who died of COVID-19, having felt frightened or isolated, and greater distress from the COVID-19 infodemic. Conclusions: This study identifies modifiable determinants of resilience among ICU staff members. Longitudinal studies are needed to determine whether prior resilience decreases the risk of mental ill health during subsequent challenges. Hospital and ICU managers, for whom preserving mental well-being among staff members is a key duty, should pay careful attention to resilience.

Protocol for fever control using external cooling in mechanically ventilated patients with septic shock: SEPSISCOOL II randomised controlled trial.

INTRODUCTION: Fever treatment is commonly applied in patients with sepsis but its impact on survival remains undetermined. Patients with respiratory and haemodynamic failure are at the highest risk for not tolerating the metabolic cost of fever. However, fever can help to control infection. Treating fever with paracetamol has been shown to be less effective than cooling. In the SEPSISCOOL pilot study, active fever control by external cooling improved organ failure recovery and early survival. The main objective of this confirmatory trial is to assess whether fever control at normothermia can improve the evolution of organ failure and mortality at day 60 of febrile patients with septic shock. This study will compare two strategies within the first 48 hours of septic shock: treatment of fever with cooling or no treatment of fever. METHODS AND ANALYSIS: SEPSISCOOL II is a pragmatic, investigator-initiated, adaptive, multicentre, open-label, randomised controlled, superiority trial in patients admitted to the intensive care unit with febrile septic shock. After stratification based on the acute respiratory distress syndrome status, patients will be randomised between two arms: (1) cooling and (2) no cooling. The primary endpoint is mortality at day 60 after randomisation. The secondary endpoints include the evolution of organ failure, early mortality and tolerance. The target sample size is 820 patients. ETHICS AND DISSEMINATION: The study is funded by the French health ministry and was approved by the ethics committee CPP Nord Ouest II (Amiens, France). The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04494074.

It takes a village: A multi-brain approach to studying multigenerational family communication.

Grandparents play a critical role in child rearing across the globe. Yet, there is a shortage of neurobiological research examining the relationship between grandparents and their grandchildren. We employ multi-brain neurocomputational models to simulate how changes in neurophysiological processes in both development and healthy aging affect multigenerational inter-brain coupling - a neural marker that has been linked to a range of socio-emotional and cognitive outcomes. The simulations suggest that grandparent-child interactions may be paired with higher inter-brain coupling than parent-child interactions, raising the possibility that the former may be more advantageous under certain conditions. Critically, this enhancement of inter-brain coupling for grandparent-child interactions is more pronounced in tri-generational interactions that also include a parent, which may speak to findings that grandparent involvement in childrearing is most beneficial if the parent is also an active household member. Together, these findings underscore that a better understanding of the neurobiological basis of cross-generational interactions is vital, and that such knowledge can be helpful in guiding interventions that consider the whole family. We advocate for a community neuroscience approach in developmental social neuroscience to capture the diversity of child-caregiver relationships in real-world settings.

Interoceptive technologies for psychiatric interventions: From diagnosis to clinical applications.

Interoception-the perception of internal bodily signals-has emerged as an area of interest due to its implications in emotion and the prevalence of dysfunctional interoceptive processes across psychopathological conditions. Despite the importance of interoception in cognitive neuroscience and psychiatry, its experimental manipulation remains technically challenging. This is due to the invasive nature of existing methods, the limitation of self-report and unimodal measures of interoception, and the absence of standardized approaches across disparate fields. This article integrates diverse research efforts from psychology, physiology, psychiatry, and engineering to address this oversight. Following a general introduction to the neurophysiology of interoception as hierarchical predictive processing, we review the existing paradigms for manipulating interoception (e.g., interoceptive modulation), their underlying mechanisms (e.g., interoceptive conditioning), and clinical applications (e.g., interoceptive exposure). We suggest a classification for interoceptive technologies and discuss their potential for diagnosing and treating mental health disorders. Despite promising results, considerable work is still needed to develop standardized, validated measures of interoceptive function across domains and before these technologies can translate safely and effectively to clinical settings.

Prospective evaluation of bleeding risk among thrombocytopenic patients admitted in intensive care unit.

PURPOSE: Bleeding risk evaluation of thrombocytopenic patients admitted in ICU has been poorly investigated. METHODS: A prospective observational study conducted in an 18-bed medical ICU. Consecutive patients with thrombocytopenia (<150 Giga/L) and no bleeding at admission were included. RESULTS: Over one year, 91 patients were included, mainly men (63%), with an age of 61 [46-68] years and a SOFA score of 6 [3-8]. Twenty-three patients (25%) had an hemorrhagic event during ICU stay, mainly digestive (n = 9; 39%) and urological (n = 6; 26%). The time between ICU admission and bleeding was 8 [2-19] days. Almost half of bleeding events required vasopressor infusion and a hemostatic procedure. At admission, two variables were significantly different between the Bleeding and No-Bleeding groups: plasma urea level was significantly higher in the Bleeding group (9 [5.1; 13] vs. 13 [8.9; 31] mmol/L; p < 0.001) and the presence of skin purpura was associated with a 3-fold higher risk for bleeding during ICU stay (HR: 3.4 [1.3-8.3]; p < 0.05). In contrast, admission platelet count was not significantly different between the 2 groups (90 [32; 128] vs 62 [36; 103] G/L; p = 0.26). CONCLUSION: Plasma urea levels and the presence of skin purpura are helpful in identifying thrombocytopenic patients at high-risk of bleeding during ICU stay.

Diagnosis and management of autoimmune diseases in the ICU.

Autoimmune diseases encompass a broad spectrum of disorders characterized by disturbed immunoregulation leading to the development of specific autoantibodies, resulting in inflammation and multiple organ involvement. A distinction should be made between connective tissue diseases (mainly systemic lupus erythematosus, systemic scleroderma, inflammatory muscle diseases, and rheumatoid arthritis) and vasculitides (mainly small-vessel vasculitis such as antineutrophil cytoplasmic antibody-associated vasculitis and immune-complex mediated vasculitis). Admission of patients with autoimmune diseases to the intensive care unit (ICU) is often triggered by disease flare-ups, infections, and organ failure and is associated with high mortality rates. Management of these patients is complex, including prompt disease identification, immunosuppressive treatment initiation, and life-sustaining therapies, and requires multi-disciplinary involvement. Data about autoimmune diseases in the ICU are limited and there is a need for multicenter, international collaboration to improve patients' diagnosis, management, and outcomes. The objective of this narrative review is to summarize the epidemiology, clinical features, and selected management of severe systemic autoimmune diseases.

Typology of ICU-Healthcare Providers Who Delayed or Declined COVID-19 Vaccination.

OBJECTIVES: To assess COVID-19 vaccination rates in ICU-healthcare providers (HCPs) in France and to identify the typology of those who delayed or declined vaccination. DESIGN: Cross-sectional study. SETTING: Twenty-one ICUs in France. SUBJECTS: Members of the nursing and medical staff and other allied professionals. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Six hundred ninety-six of the 950 respondents (73.3%) had undergone a full vaccination schedule. Other HCPs either declined vaccination ( n = 112) or delayed vaccination until it became mandatory ( n = 142). Factors independently associated with full vaccination were age older than 50 years (odds ratio, 0.25 [95% CI, 0.12-0.51]), more than 5 years of ICU experience (0.66 [0.47-0.93]), increasing working time during the surge (0.94 [0.88-1.00]), and spending time with the family (0.92 [0.85-0.99]). Conversely, being a nurse (1.94 [1.25-2.99]) or a nurse assistant (2.77 [1.62-4.73]), and feeling not supported by hospital and ICU directors (1.49 [1.01-2.20]) was independently associated with not being vaccinated. CONCLUSIONS: These results are important to take into account to better implement vaccination strategies in HCPs for existing or future pandemics.

Exploring the multidimensional nature of repetitive and restricted behaviors and interests (RRBI) in autism: neuroanatomical correlates and clinical implications.

BACKGROUND: Repetitive and restricted behaviors and interests (RRBI) are core symptoms of autism with a complex entity and are commonly categorized into 'motor-driven' and 'cognitively driven'. RRBI symptomatology depends on the individual's clinical environment limiting the understanding of RRBI physiology, particularly their associated neuroanatomical structures. The complex RRBI heterogeneity needs to explore the whole RRBI spectrum by integrating the clinical context [autistic individuals, their relatives and typical developing (TD) individuals]. We hypothesized that different RRBI dimensions would emerge by exploring the whole spectrum of RRBI and that these dimensions are associated with neuroanatomical signatures-involving cortical and subcortical areas. METHOD: A sample of 792 individuals composed of 267 autistic subjects, their 370 first-degree relatives and 155 TD individuals was enrolled in the study. We assessed the whole patterns of RRBI in each individual by using the Repetitive Behavior Scale-Revised and the Yale-Brown Obsessive Compulsive Scale. We estimated brain volumes using MRI scanner for a subsample of the subjects (n = 152, 42 ASD, 89 relatives and 13 TD). We first investigated the dimensionality of RRBI by performing a principal component analysis on all items of these scales and included all the sampling population. We then explored the relationship between RRBI-derived factors with brain volumes using linear regression models. RESULTS: We identified 3 main factors (with 30.3% of the RRBI cumulative variance): Factor 1 (FA1, 12.7%) reflected mainly the 'motor-driven' RRBI symptoms; Factor 2 and 3 (respectively, 8.8% and 7.9%) gathered mainly Y-BOCS related items and represented the 'cognitively driven' RRBI symptoms. These three factors were significantly associated with the right/left putamen volumes but with opposite effects: FA1 was negatively associated with an increased volume of the right/left putamen conversely to FA2 and FA3 (all uncorrected p < 0.05). FA1 was negatively associated with the left amygdala (uncorrected p < 0.05), and FA2 was positively associated with the left parietal structure (uncorrected p = 0.001). CONCLUSION: Our results suggested 3 coherent RRBI dimensions involving the putamen commonly and other structures according to the RRBI dimension. The exploration of the putamen's integrative role in RSBI needs to be strengthened in further studies.

Prognosis of critically ill immunocompromised patients with virus-detected acute respiratory failure.

BACKGROUND: Acute respiratory failure (ARF) is the leading cause of ICU admission. Viruses are increasingly recognized as a cause of pneumonia in immunocompromised patients, but epidemiologic data are scarce. We used the Groupe de Recherche en Réanimation Respiratoire en Onco-Hématologie's database (2003-2017, 72 intensive care units) to describe the spectrum of critically ill immunocompromised patients with virus-detected ARF and to report their outcomes. Then, patients with virus-detected ARF were matched based on clinical characteristics and severity (1:3 ratio) with patients with ARF from other origins. RESULTS: Of the 4038 immunocompromised patients in the whole cohort, 370 (9.2%) had a diagnosis of virus-detected ARF and were included in the study. Influenza was the most common virus (59%), followed by respiratory syncytial virus (14%), with significant seasonal variation. An associated bacterial infection was identified in 79 patients (21%) and an invasive pulmonary aspergillosis in 23 patients (6%). The crude in-hospital mortality rate was 37.8%. Factors associated with mortality were: neutropenia (OR = 1.74, 95% confidence interval, CI [1.05-2.89]), poor performance status (OR = 1.84, CI [1.12-3.03]), and the need for invasive mechanical ventilation on the day of admission (OR = 1.97, CI [1.14-3.40]). The type of virus was not associated with mortality. After matching, patients with virus-detected ARF had lower mortality (OR = 0.77, CI [0.60-0.98]) than patients with ARF from other causes. This result was mostly driven by influenza-like viruses, namely, respiratory syncytial virus, parainfluenza virus, and human metapneumovirus (OR = 0.54, CI [0.33-0.88]). CONCLUSIONS: In immunocompromised patients with virus-detected ARF, mortality is high, whatever the species, mainly influenced by clinical severity and poor general status. However, compared to non-viral ARF, in-hospital mortality was lower, especially for patients with detected viruses other than influenza.

Going beyond the means: Exploring the role of bias from digital determinants of health in technologies.

BACKGROUND: In light of recent retrospective studies revealing evidence of disparities in access to medical technology and of bias in measurements, this narrative review assesses digital determinants of health (DDoH) in both technologies and medical formulae that demonstrate either evidence of bias or suboptimal performance, identifies potential mechanisms behind such bias, and proposes potential methods or avenues that can guide future efforts to address these disparities. APPROACH: Mechanisms are broadly grouped into physical and biological biases (e.g., pulse oximetry, non-contact infrared thermometry [NCIT]), interaction of human factors and cultural practices (e.g., electroencephalography [EEG]), and interpretation bias (e.g, pulmonary function tests [PFT], optical coherence tomography [OCT], and Humphrey visual field [HVF] testing). This review scope specifically excludes technologies incorporating artificial intelligence and machine learning. For each technology, we identify both clinical and research recommendations. CONCLUSIONS: Many of the DDoH mechanisms encountered in medical technologies and formulae result in lower accuracy or lower validity when applied to patients outside the initial scope of development or validation. Our clinical recommendations caution clinical users in completely trusting result validity and suggest correlating with other measurement modalities robust to the DDoH mechanism (e.g., arterial blood gas for pulse oximetry, core temperatures for NCIT). Our research recommendations suggest not only increasing diversity in development and validation, but also awareness in the modalities of diversity required (e.g., skin pigmentation for pulse oximetry but skin pigmentation and sex/hormonal variation for NCIT). By increasing diversity that better reflects patients in all scenarios of use, we can mitigate DDoH mechanisms and increase trust and validity in clinical practice and research.

Sonometric assessment of cough predicts extubation failure: SonoWean-a proof-of-concept study.

BACKGROUND: Extubation failure is associated with increased mortality. Cough ineffectiveness may be associated with extubation failure, but its quantification for patients undergoing weaning from invasive mechanical ventilation (IMV) remains challenging. METHODS: Patients under IMV for more than 24 h completing a successful spontaneous T-tube breathing trial (SBT) were included. At the end of the SBT, we performed quantitative sonometric assessment of three successive coughing efforts using a sonometer. The mean of the 3-cough volume in decibels was named Sonoscore. RESULTS: During a 1-year period, 106 patients were included. Median age was 65 [51-75] years, mainly men (60%). Main reasons for IMV were acute respiratory failure (43%), coma (25%) and shock (17%). Median duration of IMV at enrollment was 4 [3-7] days. Extubation failure occurred in 15 (14%) patients. Baseline characteristics were similar between success and failure extubation groups, except percentage of simple weaning which was lower and MV duration which was longer in extubation failure patients. Sonoscore was significantly lower in patients who failed extubation (58 [52-64] vs. 75 [70-78] dB, P < 0.001). After adjustment on MV duration and comorbidities, Sonoscore remained associated with extubation failure. Sonoscore was predictive of extubation failure with an area under the ROC curve of 0.91 (IC95% [0.83-0.99], P < 0.001). A threshold of Sonoscore < 67.1 dB predicted extubation failure with a sensitivity of 0.93 IC95% [0.70-0.99] and a specificity of 0.82 IC95% [0.73-0.90]. CONCLUSION: Sonometric assessment of cough strength might be helpful to identify patients at risk of extubation failure in patients undergoing IMV.

Disorganized Communication and Social Dysfunction in Schizophrenia: Emerging Concepts and Methods.

PURPOSE OF REVIEW: In this review, we embrace the emerging field of second-person neuroscience to address disorganization in schizophrenia. We argue that the focus of interest for disorganization is the interpersonal space where shared mental processes ('social mind') occur based on the bio-behavioural synchrony between two (or more) interacting people. We lay out several bio-behavioural measures that can capture the component parts of this process. In particular, we highlight the real-time imaging technology of hyperscanning that enables multi-person analysis of naturalistic social interaction. We illustrate how these measures can be used in empirical studies by posing disorganization as a problem of interpersonal processing. RECENT FINDINGS: Traditionally, disorganized speech and behaviour have been studied as the product of hidden cognitive processes ('private mind'). A dysfunction in these processes was attributed to the brain afflicted by the illness ('brain-bound mechanisms'). But this approach has contributed to challenges in measuring and quantifying disorganization. Consequently, the single-brain focus has not provided satisfactory clarity or led to effective treatments for persistent social dysfunction in schizophrenia. Social dysfunction is a core feature of schizophrenia. This dysfunction arises from disorganized interpersonal interaction that typifies the social profile of affected individuals. We outline challenges in employing several emerging concepts and methods and how they can be addressed to investigate the mechanisms of social dysfunction in schizophrenia.

Subcortical Brain Alterations in Carriers of Genomic Copy Number Variants.

OBJECTIVE: Copy number variants (CNVs) are well-known genetic pleiotropic risk factors for multiple neurodevelopmental and psychiatric disorders (NPDs), including autism (ASD) and schizophrenia. Little is known about how different CNVs conferring risk for the same condition may affect subcortical brain structures and how these alterations relate to the level of disease risk conferred by CNVs. To fill this gap, the authors investigated gross volume, vertex-level thickness, and surface maps of subcortical structures in 11 CNVs and six NPDs. METHODS: Subcortical structures were characterized using harmonized ENIGMA protocols in 675 CNV carriers (CNVs at 1q21.1, TAR, 13q12.12, 15q11.2, 16p11.2, 16p13.11, and 22q11.2; age range, 6-80 years; 340 males) and 782 control subjects (age range, 6-80 years; 387 males) as well as ENIGMA summary statistics for ASD, schizophrenia, attention deficit hyperactivity disorder, obsessive-compulsive disorder, bipolar disorder, and major depression. RESULTS: All CNVs showed alterations in at least one subcortical measure. Each structure was affected by at least two CNVs, and the hippocampus and amygdala were affected by five. Shape analyses detected subregional alterations that were averaged out in volume analyses. A common latent dimension was identified, characterized by opposing effects on the hippocampus/amygdala and putamen/pallidum, across CNVs and across NPDs. Effect sizes of CNVs on subcortical volume, thickness, and local surface area were correlated with their previously reported effect sizes on cognition and risk for ASD and schizophrenia. CONCLUSIONS: The findings demonstrate that subcortical alterations associated with CNVs show varying levels of similarities with those associated with neuropsychiatric conditions, as well distinct effects, with some CNVs clustering with adult-onset conditions and others with ASD. These findings provide insight into the long-standing questions of why CNVs at different genomic loci increase the risk for the same NPD and why a single CNV increases the risk for a diverse set of NPDs.

Cortico-Cerebellar neurodynamics during social interaction in Autism Spectrum Disorders.

BACKGROUND: Exploring neural network dynamics during social interaction could help to identify biomarkers of Autism Spectrum Disorders (ASD). A cerebellar involvement in autism has long been suspected and recent methodological advances now enable studying cerebellar functioning in a naturalistic setting. Here, we investigated the electrophysiological activity of the cerebro-cerebellar network during real-time social interaction in ASD. We focused our analysis on theta oscillations (3-8 Hz), which have been associated with large-scale coordination of distant brain areas and might contribute to interoception, motor control, and social event anticipation, all skills known to be altered in ASD. METHODS: We combined the Human Dynamic Clamp, a paradigm for studying realistic social interactions using a virtual avatar, with high-density electroencephalography (HD-EEG). Using source reconstruction, we investigated power in the cortex and the cerebellum, along with coherence between the cerebellum and three cerebral-cortical areas, and compared our findings in a sample of participants with ASD (n = 107) and with typical development (TD) (n = 33). We developed an open-source pipeline to analyse neural dynamics at the source level from HD-EEG data. RESULTS: Individuals with ASD showed a significant increase in theta band power over the cerebellum and the frontal and temporal cortices during social interaction compared to resting state, along with significant coherence increases between the cerebellum and the sensorimotor, frontal and parietal cortices. However, a phase-based connectivity measure did not support a strict activity increase in the cortico-cerebellar functional network. We did not find any significant differences between the ASD and the TD group. CONCLUSIONS: This exploratory study uncovered increases in the theta band activity of participants with ASD during social interaction, pointing at the presence of neural interactions between the cerebellum and cerebral networks associated with social cognition. It also emphasizes the need for complementary functional connectivity measures to capture network-level alterations. Future work will focus on optimizing artifact correction to include more participants with TD and increase the statistical power of group-level contrasts.

Tri-process model of interpersonal mindfulness: theoretical framework and study protocol.

According to the Center for Disease Control and Prevention, over 14% of the US population practice mindfulness meditation. The effects of mindfulness training on physical and mental health have been consistently documented, but its effects on interpersonal relationships are not yet fully understood or investigated. Interpersonal relationships play a crucial role in the wellbeing of individuals and society, and therefore, warrants further study. The aim of this paper is to present a tri-process theoretical model of interpersonal mindfulness and a study protocol to validate the proposed model. Specifically, according to the proposed model, mindfulness meditation training increases the self-awareness, self-regulation, and prosociality of those receiving the training, which ameliorates the quality of interpersonal interactions and the socioemotional support provided to other individuals. Finally, better socioemotional support increases the support receiver's ability to regulate their emotions. Using a multiphasic longitudinal design involving 640 participants randomized into 480 dyads, the proposed protocol aims to validate the tri-process model and to investigate its mechanisms of actions. The proposed study has important theoretical and social implications and will allow devising new and more effective interpersonal mindfulness programs with applications in multiple fields.