Computational analysis on verbal fluency reveals heterogeneity in subjective language interests and brain structure

Language is an essential higher cognitive function in humans and is often affected by psychiatric and neurological disorders. Objective measures like the verbal fluency test are often used to determine language dysfunction. Recent applications of computational approaches broaden insights into language-related functions. In addition, individuals diagnosed with a psychiatric or neurological disorder also often report subjective difficulties in language-related functions. Therefore, we investigated the association between objective and subjective measures of language functioning, on the one hand, and inter-individual structural variations in language- related brain areas, on the other hand. We performed a Latent Semantic analysis (LSA) on a semantic verbal fluency task in 101 healthy adult participants. To investigate if these objective measures are associated with a subjective one, we examined assessed subjective natural tendency of interest in language-related activity with a study-specific questionnaire. Lastly, a voxel-based brain morphometry (VBM) was conducted to reveal associations between objective (LSA) measures and structural changes in language-related brain areas. We found a positive correlation between the LSA measure cosine similarity and the subjective interest in language. Furthermore, we found that higher cosine similarity corresponds to higher gray matter volume in the right cerebellum. The results suggest that people with higher interests in language access semantic knowledge in a more organized way exhibited by higher cosine similarity and have larger gray matter volume in the right cerebellum, when compared to people with lower interests. In conclusion, we demonstrate that there is inter-individual diverseness of accessing the semantic knowledge space and that it is associated with subjective language interests as well as structural differences in the right cerebellum

Resting state perfusion in the language network is linked to formal thought disorder and poor functional outcome in schizophrenia.

OBJECTIVE Formal thought disorder (FTD) is a core symptom in schizophrenia. Here, we focus on resting state cerebral blood flow (rCBF) linked to dimensions of FTD. METHODS We included 47 schizophrenia spectrum patients and 30 age- and gender-matched healthy controls. We assessed FTD with the assessment of thought, language, and communication (TLC) and imaging on a 3T MRI scanner. Within patients, we tested the association of FTD dimensions and in a subgroup (n = 27) the association of functional outcome after 6 months with whole brain rCBF. RESULTS Negative FTD was most prominently associated with perfusion within the superior temporal gyrus, while positive FTD was associated with perfusion within the supplementary motor area, and inferior frontal gyrus. Perfusion within the left supramarginal gyrus was associated with social functioning after 6 months. CONCLUSIONS Distinguishable associations of rCBF with FTD dimensions point to distinct underlying pathophysiology. The location of aberrant perfusion patterns suggests that negative FTD might reflect defective access to semantic memory while positive FTD likely reflects defective suppression of irrelevant information during increased speech production. Finally, the neural correlates of thought block were also predictive of poor functional outcome. Thus, functional outcome and distinct FTD dimensions may share some pathophysiology

The cortical signature of impaired gesturing: Findings from schizophrenia

Schizophrenia is characterized by deficits in gesturing that is important for nonverbal communication. Research in healthy participants and brain-damaged patients revealed a left-lateralized fronto-parieto-temporal network underlying gesture performance. First evidence from structural imaging studies in schizophrenia corroborates these results. However, as of yet, it is unclear if cortical thickness abnormalities contribute to impairments in gesture performance. We hypothesized that patients with deficits in gesture production show cortical thinning in 12 regions of interest (ROIs) of a gesture network relevant for gesture performance and recognition. Forty patients with schizophrenia and 41 healthy controls performed hand and finger gestures as either imitation or pantomime. Group differences in cortical thickness between patients with deficits, patients without deficits, and controls were explored using a multivariate analysis of covariance. In addition, the relationship between gesture recognition and cortical thickness was investigated. Patients with deficits in gesture production had reduced cortical thickness in eight ROIs, including the pars opercularis of the inferior frontal gyrus, the superior and inferior parietal lobes, and the superior and middle temporal gyri. Gesture recognition correlated with cortical thickness in fewer, but mainly the same, ROIs within the patient sample. In conclusion, our results show that impaired gesture production and recognition in schizophrenia is associated with cortical thinning in distinct areas of the gesture network

Treatment of Refractory Cardiac Arrest by Controlled Reperfusion of the Whole Body:A Multicenter, Prospective Observational Study

Background: Survival following cardiac arrest (CA) remains poor after conventional cardiopulmonary resuscitation (CCPR) (6–26%), and the outcomes after extracorporeal cardiopulmonary resuscitation (ECPR) are often inconsistent. Poor survival is a consequence of CA, low-flow states during CCPR, multi-organ injury, insufficient monitoring, and delayed treatment of the causative condition. We developed a new strategy to address these issues. Methods: This all-comers, multicenter, prospective observational study (69 patients with in- and out-of-hospital CA (IHCA and OHCA) after prolonged refractory CCPR) focused on extracorporeal cardiopulmonary support, comprehensive monitoring, multi-organ repair, and the potential for out-of-hospital cannulation and treatment. Result: The overall survival rate at hospital discharge was 42.0%, and a favorable neurological outcome (CPC 1+2) at 90 days was achieved for 79.3% of survivors (CPC 1+2 survival 33%). IHCA survival was very favorable (51.7%), as was CPC 1+2 survival at 90 days (41%). Survival of OHCA patients was 35% and CPC 1+2 survival at 90 days was 28%. The subgroup of OHCA patients with pre-hospital cannulation showed a superior survival rate of 57.1%. Conclusions: This new strategy focusing on repairing damage to multiple organs appears to improve outcomes after CA, and these findings should provide a sound basis for further research in this area.</p

Treatment of Refractory Cardiac Arrest by Controlled Reperfusion of the Whole Body:A Multicenter, Prospective Observational Study

Background: Survival following cardiac arrest (CA) remains poor after conventional cardiopulmonary resuscitation (CCPR) (6–26%), and the outcomes after extracorporeal cardiopulmonary resuscitation (ECPR) are often inconsistent. Poor survival is a consequence of CA, low-flow states during CCPR, multi-organ injury, insufficient monitoring, and delayed treatment of the causative condition. We developed a new strategy to address these issues. Methods: This all-comers, multicenter, prospective observational study (69 patients with in- and out-of-hospital CA (IHCA and OHCA) after prolonged refractory CCPR) focused on extracorporeal cardiopulmonary support, comprehensive monitoring, multi-organ repair, and the potential for out-of-hospital cannulation and treatment. Result: The overall survival rate at hospital discharge was 42.0%, and a favorable neurological outcome (CPC 1+2) at 90 days was achieved for 79.3% of survivors (CPC 1+2 survival 33%). IHCA survival was very favorable (51.7%), as was CPC 1+2 survival at 90 days (41%). Survival of OHCA patients was 35% and CPC 1+2 survival at 90 days was 28%. The subgroup of OHCA patients with pre-hospital cannulation showed a superior survival rate of 57.1%. Conclusions: This new strategy focusing on repairing damage to multiple organs appears to improve outcomes after CA, and these findings should provide a sound basis for further research in this area.</p

T177. STRUCTURAL ORGANIZATION OF THE PRAXIS NETWORK PREDICTS GESTURE PRODUCTION: EVIDENCE FROM HEALTHY SUBJECTS AND PATIENTS WITH SCHIZOPHRENIA

Abstract Background: Hand gestures are an integral part of social interactions and are involved in nonverbal and verbal communication. The convey language that is expressed by motor actions, and thus depend on the interplay of various brain regions. Several functional magnetic resonance imaging studies in healthy subjects suggest the praxis network for gesture production, involving distinct frontal, parietal and temporal regions. Lesions studies in subjects with apraxia, following left brain damage corroborate these findings. However, little is known about the structural connectivity underlying gesture production. We aimed to provide novel insights into the structural connectivity of the praxis network and how it is related to gesture production. Methods: Our sample consisted of 41 healthy subjects and of 40 patients with schizophrenia, demonstrating gesture impairments and structural network abnormalities. All participants performed a gesture production test, the test of upper limb apraxia and underwent diffusion weighted magnetic resonance imaging. Finsler geometry was used to investigate structural connectivity and graph theory to estimate global and local efficiency of the praxis network, which consists of 13 bilateral regions of interest. Results: Our findings showed an association of gesture production with network attributes and specific connections within the praxis network. Thus, global and local efficiency and most of the intra- and interhemispheric connections within the gesture network predicted gesture production across groups. Global efficiency of the praxis network further predicted gesture production only in the patient group. Local efficiency of many ROIs and connections of interest predicted production in patients at trend-level. In contrast, there were no significant or trend-level associations of gesture production with network attributes in controls. Discussion The results revealed an association of impaired gesture performance with structural alterations of the praxis network, including global and local efficiency and many connections of interest. Our findings are of great importance in the understanding of the structural correlates of gesture production and shed further light on the neural underpinnings of gesture deficits in a patient group with severe social deficits

Disease progression of WHIM syndrome in an international cohort of 66 pediatric and adult patients

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%). All variants affect the same CXCR4 region and impair CXCR4 internalization resulting in hyperactive signaling. The median age of diagnosis in our cohort (5.5 years) indicates WHIM syndrome can commonly present in childhood, although some patients are not diagnosed until adulthood. The prevalence and mean age of recognition and/or onset of clinical manifestations within our cohort were infections 88%/1.6 years, neutropenia 98%/3.8 years, lymphopenia 88%/5.0 years, and warts 40%/12.1 years. However, we report greater prevalence and variety of autoimmune complications of WHIM syndrome (21.2%) than reported previously. Patients with versus without family history of WHIM syndrome were diagnosed earlier (22%, average age 1.3 years versus 78%, average age 5 years, respectively). Patients with a family history of WHIM syndrome also received earlier treatment, experienced less hospitalization, and had less end-organ damage. This observation reinforces previous reports that early treatment for WHIM syndrome improves outcomes. Only one patient died; death was attributed to complications of hematopoietic stem cell transplantation. The variable expressivity of WHIM syndrome in pediatric patients delays their diagnosis and therapy. Early-onset bacterial infections with severe neutropenia and/or lymphopenia should prompt genetic testing for WHIM syndrome, even in the absence of warts

Federated learning enables big data for rare cancer boundary detection

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing.</p