Specialization of anterior and posterior hippocampal functional connectivity differs in autism.

Structural and functional differences in the hippocampus have been related to the episodic memory and social impairments observed in autism spectrum disorder (ASD). In neurotypical individuals, hippocampal-cortical functional connectivity systematically varies between anterior and posterior hippocampus, with changes observed during typical development. It remains unknown whether this specialization of anterior-posterior hippocampal connectivity is disrupted in ASD, and whether age-related differences in this specialization exist in ASD. We examined connectivity of the anterior and posterior hippocampus in an ASD (N = 139) and non-autistic comparison group (N = 133) aged 5-21 using resting-state functional magnetic resonance imaging (MRI) data from the Healthy Brain Network (HBN). Consistent with previous results, we observed lower connectivity between the whole hippocampus and medial prefrontal cortex in ASD. Moreover, preferential connectivity of the posterior relative to the anterior hippocampus for memory-sensitive regions in posterior parietal cortex was reduced in ASD, demonstrating a weaker anterior-posterior specialization of hippocampal-cortical connectivity. Finally, connectivity between the posterior hippocampus and precuneus negatively correlated with age in the ASD group but remained stable in the comparison group, suggesting an altered developmental specialization. Together, these differences in hippocampal-cortical connectivity may help us understand the neurobiological basis of the memory and social impairments found in ASD.

[Sinicization, cross-cultural adjustment and reliability and validity test of the Burnt Hand Outcome Tool].

Objective: To introduce the Burnt Hand Outcome Tool (BHOT) into China to conduct sinicization, cross-cultural debugging, and test the reliability and validity, thus provide a reference for the evaluation of treatment effect and making of medical decisions of hand burn patients. Methods: The cross-sectional research was conducted. After obtaining the authorization of the original author, the Brislin translation mode was used to literally translate, synthesize, back-translate, and be checked by experts to form the Chinese version of BHOT (C-BHOT) 2. Ten experts in the field of burn rescue and treatment were invited by purpose sampling method to conduct cross-cultural debugging to form C-BHOT 3. A total of 21 hand burn patients who were treated in General Hospital of Ningxia Medical University from January to March 2020 and conformed to the inclusion criteria were selected by accidental sampling method for pre-testing. Then the final version of C-BHOT 4 was formed. Hospitalized patients who met the selection criteria were recruited using accidental sampling, multi-site and cross-regional survey method from May 2020 to March 2021 in General Hospital of Ningxia Medical University, the First Affiliated Hospital of Air Force Medical University, the First Affiliated Hospital of Army Medical University (the Third Military Medical University), and the First Affiliated Hospital of Nanchang University. The survey was performed with the general information questionnaire and C-BHOT 4. Critical ratio method and correlation coefficient method were used for item analysis, Cronbach's α coefficient test tool was used to test internal consistency, test-retest reliability was used to judge the stability of the tool, content validity index analysis tool was used to analyze the content validity, and exploratory factor analysis was used to test the validity of the structure. Data were statistically analyzed with independent sample t test or Pearson correlation analysis. Results: After the sinicization, cross-cultural debugging, and pre-testing, C-BHOT 4 was formed with a total of 20 items. All items were adjusted to positive scoring, and 7 modifications were made on the basis of the original tool. A total of 353 questionnaires were issued in the formal survey, and 344 valid questionnaires were returned, with an effective response rate of 97.45%. In the 344 patients, there were more male patients (297 patients) than female patients (47 patients), with ages of 23 to 57 years. The critical ratios of each item in the item analysis ranged from 5.48 to 12.59 (P<0.05). There were statistically significant differences in the scores between patients in high-score group and low-score group (t=-10.72--2.84, P<0.05 or P<0.01). There was significant positive relationship among the scores of each two items and between scores of each item and the overall tool score (r=0.68-0.71, 0.47-0.63, P<0.05 or P<0.01). In reliability test, the Cronbach's α coefficient of the whole tool was 0.837, and the test-retest reliability was 0.702-0.793. In validity test, the content validity index of whole tool was 0.923. The exploratory factor analysis extracted 3 common factors, and the cumulative variance contribution rate was 76.162%. The comparative fit index in the confirmatory factor analysis was 0.924. Conclusions: After the BHOT tool being sinicized, cross-culturally debugged, pre-tested, and tested for reliability and validity, it was verified that C-BHOT 4 has good reliability and validity in assessing the outcome of Chinese hand burn patients, and therefore can be used as an effective tool for the evaluation.

Brain connectomics predict response to treatment in social anxiety disorder.

We asked whether brain connectomics can predict response to treatment for a neuropsychiatric disorder better than conventional clinical measures. Pre-treatment resting-state brain functional connectivity and diffusion-weighted structural connectivity were measured in 38 patients with social anxiety disorder (SAD) to predict subsequent treatment response to cognitive behavioral therapy (CBT). We used a priori bilateral anatomical amygdala seed-driven resting connectivity and probabilistic tractography of the right inferior longitudinal fasciculus together with a data-driven multivoxel pattern analysis of whole-brain resting-state connectivity before treatment to predict improvement in social anxiety after CBT. Each connectomic measure improved the prediction of individuals' treatment outcomes significantly better than a clinical measure of initial severity, and combining the multimodal connectomics yielded a fivefold improvement in predicting treatment response. Generalization of the findings was supported by leave-one-out cross-validation. After dividing patients into better or worse responders, logistic regression of connectomic predictors and initial severity combined with leave-one-out cross-validation yielded a categorical prediction of clinical improvement with 81% accuracy, 84% sensitivity and 78% specificity. Connectomics of the human brain, measured by widely available imaging methods, may provide brain-based biomarkers (neuromarkers) supporting precision medicine that better guide patients with neuropsychiatric diseases to optimal available treatments, and thus translate basic neuroimaging into medical practice.

Src controls neuronal migration by regulating the activity of FAK and cofilin.

Migration of postmitotic neurons in the developing cortex along radial glial fiber is essential for the formation of cortical layers. Several neurological diseases are caused by defects in neuronal migration, underlining the importance of this process for brain function. Multiple molecules are involved in this process. However, the precise mechanisms are largely unknown. In the present study, we examined the expression of Src in the developing cortex and investigated the role of Src in neuronal migration and its cellular and molecular mechanisms. Our results showed that Src was strongly expressed in the cerebral cortex during corticogenesis and mainly targeted to the leading processes of migrating neurons. Overexpression of wildtype Src (Src-WT) and its mutants, constitutively active Src (Src-CA) and dominant negative Src (Src-DN) in the mouse brain by in utero electroporation perturbed neuronal migration through affecting the adhesion properties and cytoskeletal dynamics of migrating neurons. Overexpression of Src-WT and Src-CA induced aggregation and branching of migrating neurons, whereas overexpression of Src-DN led to abnormal elongation of the leading processes of migrating neurons. Furthermore, we showed that Src activates the focal adhesion kinase (FAK) and cofilin by regulating their phosphorylation levels. We conclude that Src controls neuronal migration by regulating adhesion properties and F-actin dynamics of migrating neurons.

Radioimmunotherapy for unresectable hepatocellular carcinoma using 131I-Hepama-1 mAb: preliminary results.

Twenty-three patients with surgically verified unresectable hepatocellular carcinoma (HCC) have been treated by intrahepatic arterial administration of 131I-labeled anti-HCC monoclonal antibody (Hepama-1) combined with hepatic artery ligation. Radioimmunoimaging demonstrated that the median tumor/liver ratio was 2.1 (1.1-3.6) at day 5. A decline in alpha-fetoprotein level and shrinkage of tumor were observed in 75% (12/16) and 78% (18/23) of patients respectively. Sequential resection was done in 11 patients (48%) after treatment. The surgical specimens revealed massive necrosis of tumor, but residual cancer cells were found at the edge of the specimens. Anti-antibody was determined in 43% (10/23) of patients 2-4 weeks after the administration of 131I-Hepama-1 mAb. No marked toxic effects were noted. It is suggested that 131I-Hepama-1 mAb might be of value as one of the multimodality treatments for unresectable HCC.