The SPEAK study rationale and design: A linguistic corpus-based approach to understanding thought disorder.

AIM: Psychotic symptoms are typically measured using clinical ratings, but more objective and sensitive metrics are needed. Hence, we will assess thought disorder using the Research Domain Criteria (RDoC) heuristic for language production, and its recommended paradigm of "linguistic corpus-based analyses of language output". Positive thought disorder (e.g., tangentiality and derailment) can be assessed using word-embedding approaches that assess semantic coherence, whereas negative thought disorder (e.g., concreteness, poverty of speech) can be assessed using part-of-speech (POS) tagging to assess syntactic complexity. We aim to establish convergent validity of automated linguistic metrics with clinical ratings, assess normative demographic variance, determine cognitive and functional correlates, and replicate their predictive power for psychosis transition among at-risk youths. METHODS: This study will assess language production in 450 English-speaking individuals in Australia and Canada, who have recent onset psychosis, are at clinical high risk (CHR) for psychosis, or who are healthy volunteers, all well-characterized for cognition, function and symptoms. Speech will be elicited using open-ended interviews. Audio files will be transcribed and preprocessed for automated natural language processing (NLP) analyses of coherence and complexity. Data analyses include canonical correlation, multivariate linear regression with regularization, and machine-learning classification of group status and psychosis outcome. CONCLUSIONS: This prospective study aims to characterize language disturbance across stages of psychosis using computational approaches, including psychometric properties, normative variance and clinical correlates, important for biomarker development. SPEAK will create a large archive of language data available to other investigators, a rich resource for the field.

Linking language features to clinical symptoms and multimodal imaging in individuals at clinical high risk for psychosis.

BACKGROUND: Abnormalities in the semantic and syntactic organization of speech have been reported in individuals at clinical high-risk (CHR) for psychosis. The current study seeks to examine whether such abnormalities are associated with changes in brain structure and functional connectivity in CHR individuals. METHODS: Automated natural language processing analysis was applied to speech samples obtained from 46 CHR and 22 healthy individuals. Brain structural and resting-state functional imaging data were also acquired from all participants. Sparse canonical correlation analysis (sCCA) was used to ascertain patterns of covariation between linguistic features, clinical symptoms, and measures of brain morphometry and functional connectivity related to the language network. RESULTS: In CHR individuals, we found a significant mode of covariation between linguistic and clinical features (r = 0.73; p = 0.003), with negative symptoms and bizarre thinking covarying mostly with measures of syntactic complexity. In the entire sample, separate sCCAs identified a single mode of covariation linking linguistic features with brain morphometry (r = 0.65; p = 0.05) and resting-state network connectivity (r = 0.63; p = 0.01). In both models, semantic and syntactic features covaried with brain structural and functional connectivity measures of the language network. However, the contribution of diagnosis to both models was negligible. CONCLUSIONS: Syntactic complexity appeared sensitive to prodromal symptoms in CHR individuals while the patterns of brain-language covariation seemed preserved. Further studies in larger samples are required to establish the reproducibility of these findings.

A New Surgical Technique for Internal Shoulder Contractures Secondary to Obstetric Brachial Plexus Injury: An Anterior Coracohumeral Ligament Release.

Background Obstetric brachial plexus injuries result from traction injury during delivery; 30% of these children sustain persisting functional limitations related to an external rotation deficit of the shoulder. The aim of this study was to compare the intraoperative gain in external rotation after a posterior subscapular release and an anterior coracohumeral ligament release. Methods This is a prospective study on 102 children with an internal rotation contracture of the shoulder who received either a posterior subscapular release (posterior skin incision along the medial border of the scapula of 3-5 cm) or an anterior (5-mm skin incision) coracohumeral ligament release between 1996 and 2010. After general anesthesia, internal and external rotations in both adduction and abduction were measured before and after the surgical release. Results After a posterior subscapular release, the intraoperative external rotation improved with a mean of 64 degrees (95% confidence interval [CI]: 54-74; p < 0.001) in adduction and with a mean of 41 degrees (95% CI: 32-49; p < 0.001) in abduction. After an anterior coracohumeral ligament release, external rotation increased with a mean of 61 degrees (95% CI: 56-66; p < 0.001) in adduction and a mean of 42 degrees in abduction (95%CI: 39-45, p < 0.001). Differences between these two groups were not statistically different. Conclusion The anterior release technique shows comparable results with the posterior subscapular release. And since it is performed through a smaller incision of 5 mm, this is our preferred method to increase passive external rotation. Level of evidence II.

Developing core sets for patients with obstetricbrachial plexus injury based on the International Classificationof Functioning, Disability and Health.

BACKGROUND: Symptoms of obstetric brachial plexus injury (OBPI) vary widely over the course of time and from individual to individual and can include various degrees of denervation, muscle weakness, contractures, bone deformities and functional limitations. To date, no universally accepted overall framework is available to assess the outcome of patients with OBPI. The objective of this paper is to outline the proposed process for the development of International Classification of Functioning, Disability and Health (ICF) Core Sets for patients with an OBPI. METHODS: The first step is to conduct four preparatory studies to identify ICF categories important for OBPI: a) a systematic literature review to identify outcome measures, b) a qualitative study using focus groups, c) an expert survey and d) a cross-sectional, multicentre study. A first version of ICF Core Sets will be defined at a consensus conference, which will integrate the evidence from the preparatory studies. In a second step, field-testing among patients will validate this first version of Core Sets for OBPI. DISCUSSION: The proposed method to develop ICF Core Sets for OBPI yields a practical tool for multiple purposes: for clinicians to systematically assess and evaluate the individual's functioning, for researchers to design and compare studies, and for patients to get more insight into their health problems and their management.

Spinal glycinergic and GABAergic neurons expressing C-fos after capsaicin stimulation are increased in rats with contralateral neuropathic pain.

There is increasing evidence that pain transmission on one side of the body is influenced by a painful state on the other side. We have investigated this phenomenon by studying the activation pattern (using C-fos labeling) of spinal glycinergic and GABAergic (Gly/GABA) neurons after capsaicin injection in the ipsilateral hind paw of rats that were preconditioned with an acute or chronic pain stimulus in the contralateral hind paw or rats that were not preconditioned (control). For this purpose, fluorescent in situ hybridization with GlyT2 and GAD67 mRNA probes was combined with fluorescent C-fos immunohistochemistry. Rats were preconditioned with acute (capsaicin, Complete Freund's Adjuvant (CFA) 1.5 h), chronic inflammatory (CFA 20 h and 4 days), neuropathic (spared nerve injury (SNI) 2 weeks), or control pain stimuli (saline 20 h and 4 days; sham-SNI 2 weeks). We found that after capsaicin injection in rats preconditioned with CFA inflammation (4 days), sham-SNI or with SNI neuropathic pain, the numbers (27 ± 3, 21 ± 2, and 21 ± 2, respectively) and percentages (55% ± 4, 43% ± 2, and 42% ± 2, respectively) of C-fos activated neurons that were Gly/GABA increased significantly as compared with control (10 ± 1 and 25% ± 2). The increase in the total number of C-fos activated Gly/GABA neurons was present primarily in the superficial dorsal horn (laminae I and II; control: 9%; CFA 4 days: 56%; SNI 2 weeks: 42%). This increase in C-fos activation of Gly/GABA neurons occurred without significant changes in the total number of C-fos activated neurons, and without any significant changes in the mechanical thresholds in the hind paws after capsaicin injection. The results showed that one-sided chronic pain, especially inflammation, significantly increases the C-fos activation pattern of spinal Gly/GABA neurons on the other side of the spinal cord. This further underlines the existence of a dynamic interaction between ipsi- and contralateral spinal neurons in the processing of nociceptive information.