Specific default mode subnetworks support mentalizing as revealed through opposing network recruitment by social and semantic FMRI tasks

The ability to attribute mental states to others, or “mentalizing,” is posited to involve specific subnetworks within the overall default mode network (DMN), but this question needs clarification. To determine which default mode (DM) subnetworks are engaged by mentalizing processes, we assessed task‐related recruitment of DM subnetworks. Spatial independent component analysis (sICA) applied to fMRI data using relatively high‐order model (75 components). Healthy participants (n = 53, ages 17–60) performed two fMRI tasks: an interactive game involving mentalizing (Domino), a semantic memory task (SORT), and a resting state fMRI scan. sICA of the two tasks split the DMN into 10 subnetworks located in three core regions: medial prefrontal cortex (mPFC; five subnetworks), posterior cingulate/precuneus (PCC/PrC; three subnetworks), and bilateral temporoparietal junction (TPJ). Mentalizing events increased recruitment in five of 10 DM subnetworks, located in all three core DMN regions. In addition, three of these five DM subnetworks, one dmPFC subnetwork, one PCC/PrC subnetwork, and the right TPJ subnetwork, showed reduced recruitment by semantic memory task events. The opposing modulation by the two tasks suggests that these three DM subnetworks are specifically engaged in mentalizing. Our findings, therefore, suggest the unique involvement of mentalizing processes in only three of 10 DM subnetworks, and support the importance of the dmPFC, PCC/PrC, and right TPJ in mentalizing as described in prior studies. Hum Brain Mapp 36:3047–3063, 2015. © 2015 Wiley Periodicals, Inc.     

Comorbid posttraumatic stress disorder is associated with suicidality in male veterans with schizophrenia or schizoaffective disorder

The purpose of this study was to determine if patients with schizophrenia or schizoaffective disorders and comorbid posttraumatic stress disorder (PTSD) are at higher risk for suicidality than patients without comorbid PTSD. Participants were 165 male veterans with primary diagnoses of schizophrenia or schizoaffective disorder. Those with comorbid PTSD reported higher rates of suicidal ideation and suicidal behaviors compared to those without comorbid PTSD. These findings suggest that patients with comorbid PTSD are at higher risk for suicidality. Enhanced screening and targeted interventions may be warranted to address comorbid PTSD and increased suicide risk in this population.     

Artifact removal in the context of group ICA: A comparison of single‐subject and group approaches

Independent component analysis (ICA) has been widely applied to identify intrinsic brain networks from fMRI data. Group ICA computes group‐level components from all data and subsequently estimates individual‐level components to recapture intersubject variability. However, the best approach to handle artifacts, which may vary widely among subjects, is not yet clear. In this work, we study and compare two ICA approaches for artifacts removal. One approach, recommended in recent work by the Human Connectome Project, first performs ICA on individual subject data to remove artifacts, and then applies a group ICA on the cleaned data from all subjects. We refer to this approach as Individual ICA based artifacts Removal Plus Group ICA (IRPG). A second proposed approach, called Group Information Guided ICA (GIG‐ICA), performs ICA on group data, then removes the group‐level artifact components, and finally performs subject‐specific ICAs using the group‐level non‐artifact components as spatial references. We used simulations to evaluate the two approaches with respect to the effects of data quality, data quantity, variable number of sources among subjects, and spatially unique artifacts. Resting‐state test–retest datasets were also employed to investigate the reliability of functional networks. Results from simulations demonstrate GIG‐ICA has greater performance compared with IRPG, even in the case when single‐subject artifacts removal is perfect and when individual subjects have spatially unique artifacts. Experiments using test–retest data suggest that GIG‐ICA provides more reliable functional networks. Based on high estimation accuracy, ease of implementation, and high reliability of functional networks, we find GIG‐ICA to be a promising approach. Hum Brain Mapp 37:1005–1025, 2016. © 2015 Wiley Periodicals, Inc .     

Treatment of War Wounds: A Historical Review

The treatment of war wounds is an ancient art, constantly refined to reflect improvements in weapons technology, transportation, antiseptic practices, and surgical techniques. Throughout most of the history of warfare, more soldiers died from disease than combat wounds, and misconceptions regarding the best timing and mode of treatment for injuries often resulted in more harm than good. Since the 19th century, mortality from war wounds steadily decreased as surgeons on all sides of conflicts developed systems for rapidly moving the wounded from the battlefield to frontline hospitals where surgical care is delivered. We review the most important trends in US and Western military trauma management over two centuries, including the shift from primary to delayed closure in wound management, refinement of amputation techniques, advances in evacuation philosophy and technology, the development of antiseptic practices, and the use of antibiotics. We also discuss how the lessons of history are reflected in contemporary US practices in Iraq and Afghanistan. Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. Disclaimer: The opinions or assertions contained herein are the private views of some of the authors and are not to be construed as official or reflecting the views of the Department of Defense or the US government. This work was prepared as part of their official duties and, as such, there is no copyright to be transferred.     

Association of trauma exposure with psychiatric morbidity in military veterans who have served since September 11, 2001

Objective

This study examined the association of lifetime traumatic stress with psychiatric diagnostic status and symptom severity in veterans serving in the US military after 9/11/01.

Method

Data from 356 US military veterans were analyzed. Measures included a standardized clinical interview measure of psychiatric disorders, and paper-and-pencil assessments of trauma history, demographic variables, intellectual functioning, posttraumatic stress disorder (PTSD) symptoms, depression, alcohol misuse, and global distress.

Results

Ninety-four percent of respondents reported at least one traumatic stressor meeting DSM-IV criterion A for PTSD (i.e., life threatening event to which the person responded with fear, helplessness or horror), with a mean of four criterion A traumas. Seventy-one percent reported serving in a war-zone, with 50% reporting occurrence of an event meeting criterion A. The rate of current psychiatric disorder in this sample was: 30% PTSD, 20% major depressive disorder, 6% substance abuse or dependence and 10% for the presence of other Axis I psychiatric disorders. After accounting for demographic covariates and combat exposure, childhood physical assault and accident/disasters were most consistently associated with increased likelihood of PTSD. However, PTSD with no comorbid major depressive disorder or substance use disorder was predicted only by combat exposure and adult physical assault. Medical/unexpected-death trauma and adult physical assault were most consistently associated with more severe symptomatology.

Conclusions

Particular categories of trauma were differentially associated with the risk of psychiatric diagnosis and current symptom severity. These findings underscore the importance of conducting thorough assessment of multiple trauma exposures when evaluating recently post-deployed veterans.     

Nonlinear functional network connectivity in resting functional magnetic resonance imaging data

In this work, we focus on explicitly nonlinear relationships in functional networks. We introduce a technique using normalized mutual information (NMI) that calculates the nonlinear relationship between different brain regions. We demonstrate our proposed approach using simulated data and then apply it to a dataset previously studied by Damaraju et al. This resting‐state fMRI data included 151 schizophrenia patients and 163 age‐ and gender‐matched healthy controls. We first decomposed these data using group independent component analysis (ICA) and yielded 47 functionally relevant intrinsic connectivity networks. Our analysis showed a modularized nonlinear relationship among brain functional networks that was particularly noticeable in the sensory and visual cortex. Interestingly, the modularity appears both meaningful and distinct from that revealed by the linear approach. Group analysis identified significant differences in explicitly nonlinear functional network connectivity (FNC) between schizophrenia patients and healthy controls, particularly in the visual cortex, with controls showing more nonlinearity (i.e., higher normalized mutual information between time courses with linear relationships removed) in most cases. Certain domains, including subcortical and auditory, showed relatively less nonlinear FNC (i.e., lower normalized mutual information), whereas links between the visual and other domains showed evidence of substantial nonlinear and modular properties. Overall, these results suggest that quantifying nonlinear dependencies of functional connectivity may provide a complementary and potentially important tool for studying brain function by exposing relevant variation that is typically ignored. Beyond this, we propose a method that captures both linear and nonlinear effects in a “boosted” approach. This method increases the sensitivity to group differences compared to the standard linear approach, at the cost of being unable to separate linear and nonlinear effects.     

Correspondence of DNA Methylation Between Blood and Brain Tissue and Its Application to Schizophrenia Research

Given the difficulty of procuring human brain tissue, a key question in molecular psychiatry concerns the extent to which epigenetic signatures measured in more accessible tissues such as blood can serve as a surrogate marker for the brain. Here, we aimed (1) to investigate the blood-brain correspondence of DNA methylation using a within-subject design and (2) to identify changes in DNA methylation of brain-related biological pathways in schizophrenia.We obtained paired blood and temporal lobe biopsy samples simultaneously from 12 epilepsy patients during neurosurgical treatment. Using the Infinium 450K methylation array we calculated similarity of blood and brain DNA methylation for each individual separately. We applied our findings by performing gene set enrichment analyses (GSEA) of peripheral blood DNA methylation data (Infinium 27K) of 111 schizophrenia patients and 122 healthy controls and included only Cytosine-phosphate-Guanine (CpG) sites that were significantly correlated across tissues.Only 7.9% of CpG sites showed a statistically significant, large correlation between blood and brain tissue, a proportion that although small was significantly greater than predicted by chance. GSEA analysis of schizophrenia data revealed altered methylation profiles in pathways related to precursor metabolites and signaling peptides.Our findings indicate that most DNA methylation markers in peripheral blood do not reliably predict brain DNA methylation status. However, a subset of peripheral data may proxy methylation status of brain tissue. Restricting the analysis to these markers can identify meaningful epigenetic differences in schizophrenia and potentially other brain disorders.Key words: DNA methylation, cross-tissue, blood, brain, correlation, schizophrenia     

The effect of hyperbaric oxygen therapy of oral mucosal carcinoma

Hyperbaric oxygen is sometimes used in the course of treatment in head and neck cancer patient. This study was undertaken to investigate the effect of hyperbaric oxygen on oral cavity carcinogenesis in an animal model. Dimethylbenzanthracene was applied three times weekly to induce oral squamous cell cancers. The group that received simultaneous hyperbaric oxygen had fewer tumors, but the tumors were larger than the dimethylbenzanthracene-only group. We concluded that hyperbaric oxygen has a tumor-suppressive effect during the induction phase of oral carcinoma and appears to have a stimulatory effect during the proliferative phase of carcinoma in this animal model.