ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

German translation and psychometric testing of the Postconcussion Symptom Inventory for adolescents in self-report (PCSI-SR13) and parent-report (PCSI-P)

Adolescents are at an increased risk of sustaining a traumatic brain injury (TBI), which is associated with physical, cognitive, and/or emotional impairments, the so-called post-concussion symptoms (PCS). To fill the gap of German-language instruments for the age-appropriate assessment of PCS, the current study presents the translation, linguistic validation, and psychometric examination of two versions of the Postconcussion Symptom Inventory (PCSI) for adolescents (PCSI-SR13; 21 items) and their parents (PCSI-P; 20 items). Translation included iterative forward and backward translations and cognitive debriefings (CD). A total of 117 adolescents (aged 13–17 years) after TBI (3 months up to 10 years after injury) and 111 parents completed the PCSI. Both German versions were compared descriptively with the corresponding English versions. Analyses were conducted at the item and scale level. Confirmatory factor analyses (CFA) were performed, and internal consistency was examined using Cronbach’s α and McDonald’s ω. Convergent validity testing used Spearman’s ρ correlations with the Rivermead Post-Concussion Symptoms Questionnaire (RPQ). Cohen’s κ at the item level and intraclass correlation coefficients (ICC) were calculated to assess adolescent-parent agreement. The original four-factor structure could be replicated for the PCSI-SR13, but not for the PCSI-P. Internal consistency was good to excellent (≥ 0.80). Correlations (ρ ≥ 0.57) indicated a strong association with the RPQ. At the item level, the adolescent-parent agreement was fair to moderate (κ: 0.14–0.58). At the subscale level, interpretation of the ICC (ICC: 0.51–0.71) was limited due to the wide CI95%. In general, the psychometric properties support the applicability of the PCSI-SR13 and the PCSI-P for assessing PCS in German-speaking adolescents in the subacute and chronic phase after TBI. However, given the lack of factorial validity of the PCSI-P and the discrepancies between adolescents’ and parents’ ratings, self-report is recommended

Health-Related Quality of Life after Pediatric Traumatic Brain Injury: A Quantitative Comparison between Children’s and Parents’ Perspectives of the QOLIBRI-KID/ADO Questionnaire

Pediatric health-related quality of life (HRQoL) as a measure of subjective wellbeing and functioning has received increasing attention over the past decade. HRQoL in children and adolescents following pediatric traumatic brain injury (pTBI) has been poorly studied, and performing adequate measurements in this population is challenging. This study compares child/adolescent and parent reports of HRQoL following pTBI using the newly developed Quality of Life after Brain Injury in Children and Adolescents (QOLIBRI-KID/ADO) questionnaire. Three hundred dyads of 8–17-year-old children/adolescents and their parents were included in the study. The parent–child agreement, estimated using intraclass correlation coefficients and Cohen’s κ, displayed poor to moderate concordance. Approximately two-fifths of parents (39.3%) tended to report lower HRQoL for their children/adolescents on the total QOLIBRI-KID/ADO score. At the same time, about one-fifth (21.3%) reported higher HRQoL Total scores for their children/adolescents. The best agreement for parents rating adolescents (aged 13–17 years) was found in terms of the Total score and the Cognition and Self scale scores. To date, parent-reported HRQoL has been the preferred choice in pediatric research after TBI. However, with a parent–child disagreement of approximately 60%, our results highlight the importance of considering self-reports for children/adolescents capable of answering or completing the HRQoL measures

Task-related enhancement in corticomotor excitability during haptic sensing with the contra- or ipsilateral hand in young and senior adults

<p>Abstract</p> <p>Background</p> <p>Haptic sensing with the fingers represents a unique class of manipulative actions, engaging motor, somatosensory and associative areas of the cortex while requiring only minimal forces and relatively simple movement patterns. Using transcranial magnetic stimulation (TMS), we investigated task-related changes in motor evoked potential (MEP) amplitude associated with unimanual haptic sensing in two related experiments. In Experiment I, we contrasted changes in the excitability of the hemisphere controlling the task hand in young and old adults under two trial conditions, i.e. when participants either touched a fine grating (<it>smooth trials</it>) or touched a coarse grating to detect its groove orientation (<it>grating trials</it>). In Experiment II, the same contrast between tasks was performed but with TMS applied over the hemisphere controlling the resting hand, while also addressing hemispheric (right vs. left) and age differences.</p> <p>Results</p> <p>In Experiment I, a main effect of <it>trial type </it>on MEP amplitude was detected (p = 0.001), MEPs in the task hand being ~50% larger during grating than smooth trials. No interaction with age was detected. Similar results were found for Experiment II, <it>trial type </it>having a large effect on MEP amplitude in the resting hand (p < 0.001) owing to selective increase in MEP size (~2.6 times greater) for grating trials. No interactions with age or side (right vs. left) were detected.</p> <p>Conclusions</p> <p>Collectively, these results indicate that adding a haptic component to a simple unilateral finger action can elicit robust corticomotor facilitation not only in the working hemisphere but also in the opposite hemisphere. The fact that this facilitation seems well preserved with age, when task difficulty is adjusted, has some potential clinical implications.</p

Quality of life after brain injury in children and adolescents questionnaire – validation of the proxy version (QOLIBRI-KID/ADO-Proxy)

Background The QOLIBRI-KID/ADO-Proxy is the first disease-specific health-related quality of life (HRQoL) proxy questionnaire developed for use in the field of pediatric traumatic brain injury (TBI), when children are unable to report their HRQoL themselves. Methods Its psychometric properties in a German-speaking context are examined in two samples (development and validation). Dyads of 600 parents and their children (aged 8–17 years) were included. Results The 35-item questionnaire covers six dimensions (Cognition, Self, Daily Life and Autonomy, Social Relationships, Emotions, and Physical Problems). Results showed good to excellent internal consistencies, acceptable test-retest reliability, and low to fair parent-child agreement. Confirmatory factor analyses supported the one-level six-factor structure. In terms of construct validity, there was an overlap between the disease-specific and the generic HRQoL. Lower parent-reported HRQoL in children was associated with lower parental education, lower functional recovery (Study I), more recent TBI, and more severe depressive, anxiety, and post-concussion symptoms. Findings differed between the two studies in terms of age, gender, and TBI severity. Study I found more severe TBI linked to lower HRQoL in adolescents, while Study II indicated lower HRQoL ratings in girls. Conclusion The QOLIBRI-KID/ADO-Proxy is recommended when individuals are unable to self-report their HRQoL

Linking Symptom Inventories using Semantic Textual Similarity

An extensive library of symptom inventories has been developed over time to measure clinical symptoms, but this variety has led to several long standing issues. Most notably, results drawn from different settings and studies are not comparable, which limits reproducibility. Here, we present an artificial intelligence (AI) approach using semantic textual similarity (STS) to link symptoms and scores across previously incongruous symptom inventories. We tested the ability of four pre-trained STS models to screen thousands of symptom description pairs for related content - a challenging task typically requiring expert panels. Models were tasked to predict symptom severity across four different inventories for 6,607 participants drawn from 16 international data sources. The STS approach achieved 74.8% accuracy across five tasks, outperforming other models tested. This work suggests that incorporating contextual, semantic information can assist expert decision-making processes, yielding gains for both general and disease-specific clinical assessment

Remodeling of the Cortical Structural Connectome in Posttraumatic Stress Disorder:Results from the ENIGMA-PGC PTSD Consortium

BACKGROUND: Posttraumatic stress disorder (PTSD) is accompanied by disrupted cortical neuroanatomy. We investigated alteration in covariance of structural networks associated with PTSD in regions that demonstrate the case-control differences in cortical thickness (CT) and surface area (SA). METHODS: Neuroimaging and clinical data were aggregated from 29 research sites in >1,300 PTSD cases and >2,000 trauma-exposed controls (age 6.2-85.2 years) by the ENIGMA-PGC PTSD working group. Cortical regions in the network were rank-ordered by effect size of PTSD-related cortical differences in CT and SA. The top-n (n = 2 to 148) regions with the largest effect size for PTSD > non-PTSD formed hypertrophic networks, the largest effect size for PTSD < non-PTSD formed atrophic networks, and the smallest effect size of between-group differences formed stable networks. The mean structural covariance (SC) of a given n-region network was the average of all positive pairwise correlations and was compared to the mean SC of 5,000 randomly generated n-region networks. RESULTS: Patients with PTSD, relative to non-PTSD controls, exhibited lower mean SC in CT-based and SA-based atrophic networks. Comorbid depression, sex and age modulated covariance differences of PTSD-related structural networks. CONCLUSIONS: Covariance of structural networks based on CT and cortical SA are affected by PTSD and further modulated by comorbid depression, sex, and age. The structural covariance networks that are perturbed in PTSD comport with converging evidence from resting state functional connectivity networks and networks impacted by inflammatory processes, and stress hormones in PTSD