Linking enlarged choroid plexus with plasma analyte and structural phenotypes in clinical high risk for psychosis: A multisite neuroimaging study.

BACKGROUND: Choroid plexus (ChP) enlargement exists in first-episode and chronic psychosis, but whether enlargement occurs before psychosis onset is unknown. This study investigated whether ChP volume is enlarged in individuals with clinical high-risk (CHR) for psychosis and whether these changes are related to clinical, neuroanatomical, and plasma analytes. METHODS: Clinical and neuroimaging data from the North American Prodrome Longitudinal Study 2 (NAPLS2) was used for analysis. 509 participants (169 controls, 340 CHR) were recruited. Conversion status was determined after 2-years of follow-up, with 36 psychosis converters. The lateral ventricle ChP was manually segmented from baseline scans. A subsample of 31 controls and 53 CHR had plasma analyte and neuroimaging data. RESULTS: Compared to controls, CHR (d = 0.23, p = 0.017) and non-converters (d = 0.22, p = 0.03) demonstrated higher ChP volumes, but not in converters. In CHR, greater ChP volume correlated with lower cortical (r = -0.22, p < 0.001), subcortical gray matter (r = -0.21, p < 0.001), and total white matter volume (r = -0.28,p < 0.001), as well as larger lateral ventricle volume (r = 0.63,p < 0.001). Greater ChP volume correlated with makers functionally associated with the lateral ventricle ChP in CHR [CCL1 (r = -0.30, p = 0.035), ICAM1 (r = 0.33, p = 0.02)], converters [IL1ß (r = 0.66, p = 0.004)], and non-converters [BMP6 (r = -0.96, p < 0.001), CALB1 (r = -0.98, p < 0.001), ICAM1 (r = 0.80, p = 0.003), SELE (r = 0.59, p = 0.026), SHBG (r = 0.99, p < 0.001), TNFRSF10C (r = 0.78, p = 0.001)]. CONCLUSIONS: CHR and non-converters demonstrated significantly larger ChP volumes compared to controls. Enlarged ChP was associated with neuroanatomical alterations and analyte markers functionally associated with the ChP. These findings suggest that the ChP may be a key an important biomarker in CHR.

Treating acute exacerbations of COPD with Chinese herbal medicine to aid antibiotic use reduction (Excalibur): a randomised double-blind, placebo-controlled feasibility trial.

Background: Although many acute exacerbations of COPD (AECOPD) are triggered by non-bacterial causes, they are often treated with antibiotics. Preliminary research suggests that the Chinese herbal medicine "Shufeng Jiedu" (SFJD), may improve recovery and therefore reduce antibiotic use in patients with AECOPD. Aims: To assess the feasibility of conducting a randomised placebo-controlled clinical trial of SFJD for AECOPD in UK primary care. Methods: GPs opportunistically recruited patients experiencing an AECOPD. Participants were randomised 1:1 to usual care plus SFJD or placebo for 14 days. Participants, GPs and research nurses were blinded to treatment allocation. GPs could prescribe immediate, delayed or no antibiotics, with delayed prescribing encouraged where appropriate. Participants were asked to complete a participant diary, including EXACT-PRO and CAT™ questionnaires for up to 4 weeks. Outcomes included recruitment rate and other measures of study feasibility described using only descriptive statistics and with no formal comparisons between groups. We also conducted qualitative interviews with recruited and non-recruited COPD patients and clinicians, analysed using framework analysis. Results: Over 6 months, 19 participants (6 SFJD, 13 placebo) were recruited. Sixteen (84%) participants returned diaries or provided a diary by recall. Overall, 1.3 participants were recruited per 1,000 patients on the COPD register per month open. Median duration of treatment was 9.8 days in the intervention group vs 13.3 days in the placebo group. The main reason for discontinuation in both groups was perceived side-effects. in both groups. Point estimates for both the EXACT-PRO and CAT™ outcomes suggested possible small benefits of SFJD. Most patients and clinicians were happy to try SFJD as an alternative to antibiotics for AECOPD. Recruitment was lower than expected because of the short recruitment period, the lower incidence of AECOPD during the COVID-19 pandemic, patients starting antibiotics from "rescue packs" before seeing their GP, and workforce challenges in primary care. Conclusion: Recruitment was impaired by the COVID-19 pandemic. Nevertheless, we were able to demonstrate the feasibility of recruiting and randomising participants and identified approaches to address recruitment challenges such as including the trial medication in COPD patients' "rescue packs" and delegating recruitment to a central trials team. Clinical Trial Registration: Identifier, ISRCTN26614726.

Systematic review on gene-sun exposure interactions in skin cancer.

BACKGROUND: The risk of skin cancer is determined by environmental factors like ultraviolet radiation (UVR), personal habits like time spent outdoors and genetic factors. This review aimed to survey existing studies in gene-environment (GxE) interaction on skin cancer risk, and report on GxE effect estimates. METHODS: We searched Embase, Medline (Ovid) and Web of Science (Core Collection) and included only primary research that reported on GxE on the risk of the three most common types of skin cancer: basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma. Quality assessment followed the Newcastle-Ottawa Scale. Meta-analysis was not possible because no two studies examined the same interaction. This review was registered on PROSPERO (CRD42021238064). RESULTS: In total 260 records were identified after exclusion of duplicates. Fifteen studies were included in the final synthesis-12 used candidate gene approach. We found some evidence of GxE interactions with sun exposure, notably, with MC1R, CAT and NOS1 genes in melanoma, HAL and IL23A in BCC and HAL and XRCC1 in SCC. CONCLUSION: Sun exposure seems to interact with genes involved in pigmentation, oxidative stress and immunosuppression, indicating that excessive UV exposure might exhaust oxidative defence and repair systems differentially, dependent on genetic make-up. Further research is warranted to better understand skin cancer epidemiology and develop sun exposure recommendations. A genome-wide approach is recommended as it might uncover unknown disease pathways dependent on UV radiation.

Ray-tracing-guided myopic LASIK: real-world clinical outcomes.

PURPOSE: To assess effectiveness of individualized ray-trace based laser in situ keratomileusis (LASIK) for correction of myopia in everyday clinical practice. SETTING: Single-site private practice. DESIGN: Retrospective nonrandomised unmasked chart review. METHODS: Consecutive, myopic eyes (range ≤-8.25 diopters [D] sphere; astigmatism 0 to -4.25 D) treated with ray-trace based LASIK were included. Patients underwent wavefront, tomography, and biometry assessment using the InnovEyes Sightmap diagnostic device. The ray-trace based algorithm (InnovEyes algorithm) then generated an individualized 3D eye model and calculated a customized LASIK ablation profile. Postoperative visual acuity, refractive error and whole eye higher-order aberrations (HOAs) were evaluated over 3 months. RESULTS: The procedure was performed on 400 eyes (200 patients). Mean preoperative manifest refraction spherical equivalent was -3.39 ± 1.58 D (right eye -3.84 ± 1.63 D, left eye -3.98 ± 1.75 D). At month 3, uncorrected distance visual acuity (UDVA) was ≥20/20 in all eyes, ≥20/16 in 89% (right eye 90%, left eye 89%), ≥20/12 in 51% (54% right eye; 47% left eye), and 20/10 in 8% (right eye 8%; left eye 9%) of eyes respectively. UDVA was within 1 line of preoperative corrected distance visual acuity in 98% of eyes (right eye 98.5%; left eye 98%) and 39% of eyes (right eye 38%; left eye 39%) gained 1 line improvement. There was a statistically but not clinically significant increase in total HOAs (right eye 0.06 ± 0.133 µm; left eye 0.057 ± 0.125 µm; P < .001). The spherical aberration decreased (right eye -0.047 ± 0.095 µm, P < .001; left eye -0.051 ± 0.091 µm, P < .001). CONCLUSIONS: Ray-trace based LASIK was safe and effective for correction of myopia with and without astigmatism. Approximately, half the eyes achieved ≥20/12.5 UDVA and 8% achieved 20/10. There was no clinically significant increase in total whole eye HOAs.

Ketamine Effects on Energy Metabolism, Functional Connectivity and Working Memory in Healthy Humans.

Working memory (WM) is a crucial resource for temporary memory storage and the guiding of ongoing behavior. N-methyl-D-aspartate glutamate receptors (NMDARs) are thought to support the neural underpinnings of WM. Ketamine is an NMDAR antagonist that has cognitive and behavioral effects at subanesthetic doses. To shed light on subanesthetic ketamine effects on brain function, we employed a multimodal imaging design, combining gas-free calibrated functional magnetic resonance imaging (fMRI) measurement of oxidative metabolism (CMRO 2 ), resting-state cortical functional connectivity assessed with fMRI, and WM-related fMRI. Healthy subjects participated in two scan sessions in a randomized, double-blind, placebo-controlled design. Ketamine increased CMRO 2 and cerebral blood flow (CBF) in prefrontal cortex (PFC) and other cortical regions. However, resting-state cortical functional connectivity was not affected. Ketamine did not alter CBF-CMRO 2 coupling brain-wide. Higher levels of basal CMRO 2 were associated with lower task-related PFC activation and WM accuracy impairment under both saline and ketamine conditions. These observations suggest that CMRO 2 and resting-state functional connectivity index distinct dimensions of neural activity. Ketamine’s impairment of WM-related neural activity and performance appears to be related to its ability to produce cortical metabolic activation. This work illustrates the utility of direct measurement of CMRO 2 via calibrated fMRI in studies of drugs that potentially affect neurovascular and neurometabolic coupling.

Nasal turbinate mucosal graft for management of contracted anophthalmic socket.

A 67-year-old Caucasian male presented with severe contraction of socket lining 8 years after enucleation, dermis fat graft and successful ocular prosthesis fitting. Following two failed attempts at using amniotic membrane grafts to reform the socket lining, a total socket reconstruction was attempted using a novel nasal turbinate mucosal graft technique. This was performed in a staged fashion with lower fornix reconstruction followed by upper fornix reconstruction 3 months later. The patient was stable at 12 months review, with a satisfactory cosmetic outcome. Nasal turbinate mucosa was used as it was surgically accessible, provided natural socket lubrication due to its mucosal surface, and avoided oral mucosa and its associated morbidity. This case report suggests that nasal turbinate mucosa is a suitable autologous grafting material for total socket reconstruction in contracted anophthalmic sockets.

Influence of Ocular Surface Hydration on Intra-Operative Aberrometry Measurement and Toric Intraocular Lens Recommendation.

Purpose: The purpose of this study was to examine the effect of intra-operative live refraction stability as a surrogate marker of ocular surface hydration on intra-operative aberrometry (IA) results and to quantify the minimum duration of stable refraction needed to achieve accurate intraocular lens (IOL) selection. Methods: In this nonrandomized consecutive retrospective chart review, 18,000 data points from 45 live refraction runs of 15 patients were digitized and analyzed. An objective automated moving average method of frames lengths of 88 ms, 110 ms, and 132 ms with less than 0.5 diopters (D) of fluctuation was compared to raw IA capture data. The difference-vector (DV) of the predicted toric powers was compared among these groups. Subjectively, traces were classified as stable or unstable if the live refraction fluctuated less than 0.5 D for 5 seconds. The DV based on the stable period was compared with the IA capture data. Results: The DVs for all frame intervals showed no significant difference when compared with IA readings. In 15 of 45 (33.3%) cases, IA active refraction traces were stable and the DV (0.27 D ± 0.15 D) was significantly less than unstable traces (0.49 D ± 0.28 D). IOL recommendations from 14 (93.3%) of stable runs led to a <0.5 D of postoperative cylinder compared to 14 (47.7%) in unstable runs. Conclusions: Intra-operative live refraction stability is affected by ocular hydration. Surgeons should look for periods of refractive stability for at least 5 seconds to better assess measurement quality. This can be facilitated by capturing and including the active refraction trace, which is currently unavailable for review. Translational Relevance: Graphing live refractive IA readings and determining refractive stability translates to more accurate IOL selection.

An update on the current epidemiological status of metastatic neoplasms to the thyroid.

Secondary tumours to the thyroid gland are uncommon with an overall prevalence of 5.9% in autopsy studies. In recent clinical series, secondary thyroid cancer is seen in only 1.9% of malignant thyroids. There is no gender predominance both overall (female to male 1.07:1) and when stratified by common histological subtypes (renal cell carcinoma, lung adenocarcinoma and colorectal adenocarcinoma). The median age of patients diagnosed with metastatic thyroid tumours in major studies ranges from 54 to 68 years. Metastases are more frequent in patients with pre-existing or concurrent thyroid pathology. In autopsy studies, the most common primary sites are breast carcinoma and lung carcinoma. Renal cell carcinoma, lung carcinoma and breast carcinoma predominate in clinical series. Upper aerodigestive tract primaries often directly infiltrate the thyroid gland. The underlying frequency of a histological subtype, geographic prevalence and aggressiveness of primary cancer likely contributes to the incidence of metastasis in the thyroid gland. This is seen in case series from Asia where gastric and oesophageal primary cancers predominate. Secondary thyroid cancer can present metachronously (60%), synchronously (34%), or as the first presentation of the underlying cancer (6%). Late metastases and first clinical presentations of disease often originate from renal cell carcinomas while synchronous cases tend to originate from the lungs. Other common primary sites for first presentation of secondary thyroid cancer include the lung and oesophagus. Although rare, secondary thyroid cancer should be considered as a differential particularly in patients with previous malignancy, such as from the kidney, lung, or breast.

Fundoscopy use in neurology departments and the utility of smartphone photography: a prospective prevalence and crossover diagnostic accuracy study amongst neurology inpatients.

BACKGROUND AND PURPOSE: Although fundoscopy is a crucial part of the neurological examination, it is challenging, under-utilized and unreliably performed. The aim was to determine the prevalence of fundus pathology amongst neurology inpatients and the diagnostic accuracy of current fundoscopy practice compared with systematic screening with smartphone fundoscopy (SF) and portable non-mydriatic fundus photography (NMFP). METHODS: This was a prospective cross-sectional surveillance and diagnostic accuracy study on adult patients admitted under neurology in an Australian hospital. Inpatients were randomized to initial NMFP (RetinaVue 100, Welch Allyn) or SF (D-EYE) followed by a crossover to the alternative modality. Images were graded by neurology doctors, using telemedicine consensus neuro-ophthalmology NMFP grading as the reference standard. Feasibility parameters included ease, comfort and speed. RESULTS: Of 79 enrolled patients, 14.1% had neurologically relevant pathology (seven, disc pallor; one, hypertensive retinopathy; three, disc swelling). The neurology team performed direct ophthalmoscopy in 6.6% of cases and missed all abnormalities. SF had a sensitivity of 30%-40% compared with NMFP (45.5%); however, it had a lower rate of screening failure (1% vs. 13%, p < 0.001), a shorter examination time (1.10 vs. 2.25 min, p < 0.001) and a slightly higher patient comfort rating (9.2 vs. 8/10, p < 0.001). CONCLUSION: Our study demonstrates a clinically significant prevalence of fundus pathology amongst neurology inpatients which was missed by current fundoscopy practices. Portable NMFP screening appears more accurate than SF, whilst both are diagnostically superior to routine fundoscopic practice, feasible and well tolerated by patients.

Clinicopathological and Molecular Features of Secondary Cancer (Metastasis) to the Thyroid and Advances in Management.

Secondary tumours to the thyroid gland are uncommon and often incidentally discovered on imaging. Symptomatic patients often present with a neck mass. Collision tumours of secondary tumours and primary thyroid neoplasms do occur. Ultrasound-guided fine-needle aspiration, core-needle biopsy, and surgical resection with histological and immunohistochemical analysis are employed to confirm diagnosis as well as for applying molecular studies to identify candidates for targeted therapy. Biopsy at the metastatic site can identify mutations (such as EGFR, K-Ras, VHL) and translocations (such as EML4-ALK fusion) important in planning target therapies. Patients with advanced-stage primary cancers, widespread dissemination, or unknown primary origin often have a poor prognosis. Those with isolated metastasis to the thyroid have better survival outcomes and are more likely to undergo thyroid resection. Systemic therapies, such as chemotherapy and hormonal therapy, are often used as adjuvant treatment post-operatively or in patients with disseminated disease. New targeted therapies, such as tyrosine kinase inhibitors and immune checkpoint inhibitors, have shown success in reported cases. A tailored treatment plan based on primary tumour features, overall cancer burden, and co-morbidities is imperative. To conclude, secondary cancer to the thyroid is uncommon, and awareness of the updates on diagnosis and management is needed.

Amygdala-prefrontal connectivity in children with maladaptive aggression is modulated by social impairment.

Aggressive behavior is common across childhood-onset psychiatric disorders and is associated with impairments in social cognition and communication. The present study examined whether amygdala connectivity and reactivity during face emotion processing in children with maladaptive aggression are moderated by social impairment. This cross-sectional study included a well-characterized transdiagnostic sample of 101 children of age 8-16 years old with clinically significant levels of aggressive behavior and 32 typically developing children without aggressive behavior. Children completed a face emotion perception task of fearful and calm faces during functional magnetic resonance imaging. Aggressive behavior and social functioning were measured by standardized parent ratings. Relative to controls, children with aggressive behavior showed reduced connectivity between the amygdala and the dorsolateral prefrontal cortex (PFC) during implicit emotion processing. In children with aggressive behavior, the association between reduced amygdala-ventrolateral PFC connectivity and greater severity of aggression was moderated by greater social impairment. Amygdala reactivity to fearful faces was also associated with severity of aggressive behavior for children without social deficits but not for children with social deficits. Social impairments entail difficulties in interpreting social cues and enacting socially appropriate responses to frustration or provocation, which increase the propensity for an aggressive response via diminished connectivity between the amygdala and the ventral PFC.

Large-scale functional brain networks of maladaptive childhood aggression identified by connectome-based predictive modeling.

Disruptions in frontoparietal networks supporting emotion regulation have been long implicated in maladaptive childhood aggression. However, the association of connectivity between large-scale functional networks with aggressive behavior has not been tested. The present study examined whether the functional organization of the connectome predicts severity of aggression in children. This cross-sectional study included a transdiagnostic sample of 100 children with aggressive behavior (27 females) and 29 healthy controls without aggression or psychiatric disorders (13 females). Severity of aggression was indexed by the total score on the parent-rated Reactive-Proactive Aggression Questionnaire. During fMRI, participants completed a face emotion perception task of fearful and calm faces. Connectome-based predictive modeling with internal cross-validation was conducted to identify brain networks that predicted aggression severity. The replication and generalizability of the aggression predictive model was then tested in an independent sample of children from the Adolescent Brain Cognitive Development (ABCD) study. Connectivity predictive of aggression was identified within and between networks implicated in cognitive control (medial-frontal, frontoparietal), social functioning (default mode, salience), and emotion processing (subcortical, sensorimotor) (r = 0.31, RMSE = 9.05, p = 0.005). Out-of-sample replication (p < 0.002) and generalization (p = 0.007) of findings predicting aggression from the functional connectome was demonstrated in an independent sample of children from the ABCD study (n = 1791; n = 1701). Individual differences in large-scale functional networks contribute to variability in maladaptive aggression in children with psychiatric disorders. Linking these individual differences in the connectome to variation in behavioral phenotypes will advance identification of neural biomarkers of maladaptive childhood aggression to inform targeted treatments.

Image based deep learning in 12-lead ECG diagnosis.

Background: The electrocardiogram is an integral tool in the diagnosis of cardiovascular disease. Most studies on machine learning classification of electrocardiogram (ECG) diagnoses focus on processing raw signal data rather than ECG images. This presents a challenge for models in many areas of clinical practice where ECGs are printed on paper or only digital images are accessible, especially in remote and regional settings. This study aims to evaluate the accuracy of image based deep learning algorithms on 12-lead ECG diagnosis. Methods: Deep learning models using VGG architecture were trained on various 12-lead ECG datasets and evaluated for accuracy by testing on holdout test data as well as data from datasets not seen in training. Grad-CAM was utilized to depict heatmaps of diagnosis. Results: The results demonstrated excellent AUROC, AUPRC, sensitivity and specificity on holdout test data from datasets used in training comparable to the best signal and image-based models. Detection of hidden characteristics such as gender were achieved at a high rate while Grad-CAM successfully highlight pertinent features on ECGs traditionally used by human interpreters. Discussion: This study demonstrates feasibility of image based deep learning algorithms in ECG diagnosis and identifies directions for future research in order to develop clinically applicable image based deep-learning models in ECG diagnosis.

Biomarkers for Precision Urothelial Carcinoma Diagnosis: Current Approaches and the Application of Single-Cell Technologies.

Urothelial carcinoma (UC) is the most frequent malignancy of the urinary system and is ranked the sixth most diagnosed cancer in men worldwide. Around 70-75% of newly diagnosed UC manifests as the non-muscle invasive bladder cancer (NMIBC) subtype, which can be treated by a transurethral resection of the tumor. However, patients require life-long monitoring due to its high rate of recurrence. The current gold standard for UC diagnosis, prognosis, and disease surveillance relies on a combination of cytology and cystoscopy, which is invasive, costly, and associated with comorbidities. Hence, there is considerable interest in the development of highly specific and sensitive urinary biomarkers for the non-invasive early detection of UC. In this review, we assess the performance of current diagnostic assays for UC and highlight some of the most promising biomarkers investigated to date. We also highlight some of the recent advances in single-cell technologies that may offer a paradigm shift in the field of UC biomarker discovery and precision diagnostics.

Sex differences in medial prefrontal and parietal cortex structure in children with disruptive behavior.

Sex differences in brain structure in children with disruptive behavior disorders (DBD) remain poorly understood. This study examined sex differences in gray matter volume in children with DBD in a priori regions-of-interest implicated in the pathophysiology of disruptive behavior. We then conducted a whole-brain analysis of cortical thickness to examine sex differences in regions not included in our hypothesis. Exploratory analyses investigated unique associations between structure, and dimensional measures of severity of disruptive behavior and callous-unemotional traits. This cross-sectional study included 88 children with DBD (30 females) aged 8-16 years and 50 healthy controls (20 females). Structural MRI data were analyzed using surface-based morphometry to test for interactions between sex and group. Multiple-regression analyses tested for sex-specific associations between structure, callous-unemotional traits, and disruptive behavior severity. Boys with DBD showed reduced gray matter volume in the left ventromedial prefrontal cortex (vmPFC) and reduced cortical thickness in the supramarginal gyrus, but not girls compared to respective controls. Dimensional analyses revealed associations between sex, callous-unemotional traits, and disruptive behavior for amygdala and vmPFC volume, and ventrolateral prefrontal cortex cortical thickness. Sex-specific differences in prefrontal structures involved in emotion regulation may support identification of neural biomarkers of disruptive behavior to inform target-based treatments.

Mango: Exploratory Data Analysis for Large-Scale Sequencing Datasets.

The decreasing cost of DNA sequencing over the past decade has led to an explosion of sequencing datasets, leaving us with petabytes of data to analyze. However, current sequencing visualization tools are designed to run on single machines, which limits their scalability and interactivity on modern genomic datasets. Here, we leverage the scalability of Apache Spark to provide Mango, consisting of a Jupyter notebook and genome browser, which removes scalability and interactivity constraints by leveraging multi-node compute clusters to allow interactive analysis over terabytes of sequencing data. We demonstrate scalability of the Mango tools by performing quality control analyses on 10 terabytes of 100 high-coverage sequencing samples from the Simons Genome Diversity Project, enabling capability for interactive genomic exploration of multi-sample datasets that surpass the computational limitations of single-node visualization tools. Mango is freely available for download with full documentation at https://bdg-mango.readthedocs.io/en/latest/.

Reduced Amygdala-Prefrontal Functional Connectivity in Children With Autism Spectrum Disorder and Co-occurring Disruptive Behavior.

BACKGROUND: Disruptive behaviors are prevalent in children with autism spectrum disorder (ASD) and often cause substantial impairments. However, the underlying neural mechanisms of disruptive behaviors remain poorly understood in ASD. In children without ASD, disruptive behavior is associated with amygdala hyperactivity and reduced connectivity with the ventrolateral prefrontal cortex (vlPFC). This study examined amygdala reactivity and connectivity in children with ASD with and without co-occurring disruptive behavior disorders. We also investigated differential contributions of externalizing behaviors and callous-unemotional traits to variance in amygdala connectivity and reactivity. METHODS: This cross-sectional study involved behavioral assessments and neuroimaging in three groups of children 8 to 16 years of age: 18 children had ASD and disruptive behavior, 20 children had ASD without disruptive behavior, and 19 children were typically developing control participants matched for age, gender, and IQ. During functional magnetic resonance imaging, participants completed an emotion perception task of fearful versus calm faces. Task-specific changes in amygdala reactivity and connectivity were examined using whole-brain, psychophysiological interaction, and multiple regression analyses. RESULTS: Children with ASD and disruptive behavior showed reduced amygdala-vlPFC connectivity compared with children with ASD without disruptive behavior. Externalizing behaviors and callous-unemotional traits were associated with amygdala reactivity to fearful faces in children with ASD after controlling for suppressor effects. CONCLUSIONS: Reduced amygdala-vlPFC connectivity during fear processing may differentiate children with ASD and disruptive behavior from children with ASD without disruptive behavior. The presence of callous-unemotional traits may have implications for identifying differential patterns of amygdala activity associated with increased risk of aggression in ASD. These findings suggest a neural mechanism of emotion dysregulation associated with disruptive behavior in children with ASD.

Altered functional connectivity and low-frequency signal fluctuations in early psychosis and genetic high risk.

Studying individuals at increased genetic risk for schizophrenia may generate important theories regarding the emergence of the illness. In this investigation, genetic high-risk individuals (GHR, n = 37) were assessed with functional magnetic resonance imaging and compared to individuals in the first episode of schizophrenia (FESZ, n = 42) and healthy comparison subjects (HCS, n = 59). Measures of functional connectivity and the amplitude of low-frequency fluctuation (ALFF) were obtained in a global, data-driven analysis. The functional connectivity measure, termed degree centrality, assessed each voxel's connectivity with all the other voxels in the brain. GHR and FESZ displayed increased degree centrality globally and locally. On ALFF measures, GHR were indistinguishable from HCS in the majority of areas but resembled FESZ in insula, basal ganglia and hippocampus. FESZ evidenced reduced amplitude of the global neural signal as compared to HCS and GHR. Results support the hypothesis that schizophrenia diathesis involves functional connectivity and ALFF abnormalities. In addition, they further an emerging theory suggesting that increased connectivity and metabolism may be involved in schizophrenia vulnerability and early stages of the illness.

Ventricular enlargement and progressive reduction of cortical gray matter are linked in prodromal youth who develop psychosis.

In a recent prospective longitudinal neuroimaging study, clinical high-risk (CHR) individuals who later developed full-blown psychosis showed an accelerated rate of gray matter thinning in superior and medial prefrontal cortex (PFC) and expansion of the ventricular system after applying a stringent correction for multiple comparisons. Although cortical and subcortical volume loss and enlarged ventricles are well characterized structural brain abnormalities among patients with schizophrenia, no prior study has evaluated whether these progressive changes of neuroanatomical indicators are linked in time prior to onset of psychosis. Therefore, we investigated the relationship between the changes in cortical gray matter thickness and ventricular volume using the longitudinal neuroimaging data from the North American Prodrome Longitudinal Study at the whole-brain level. The results showed that ventricular expansion is linked in time to progressive reduction of gray matter, rather than to structural changes in proximal subcortical regions, in a broadly distributed set of cortical regions among CHR youth, including superior, medial, lateral, and inferior PFC, superior temporal gyrus, and parietal cortices. In contrast, healthy controls did not show the same pattern of associations. The main findings were further replicated using a third assessment wave of MRI scans in a subset of study participants who were followed for an additional year. These findings suggest that the gray matter regions exhibiting aberrant rates of thinning in relation to psychosis risk are not limited to the PFC regions that survived the statistical threshold in our primary study, but also extend to other cortical regions previously implicated in schizophrenia.