Brain electric correlates of strong belief in paranormal phenomena: intracerebral EEG source and regional Omega complexity analyses

The neurocognitive processes underlying the formation and maintenance of paranormal beliefs are important for understanding schizotypal ideation. Behavioral studies indicated that both schizotypal and paranormal ideation are based on an overreliance on the right hemisphere, whose coarse rather than focussed semantic processing may favor the emergence of 'loose' and 'uncommon' associations. To elucidate the electrophysiological basis of these behavioral observations, 35-channel resting EEG was recorded in pre-screened female strong believers and disbelievers during resting baseline. EEG data were subjected to FFT-Dipole-Approximation analysis, a reference-free frequency-domain dipole source modeling, and Regional (hemispheric) Omega Complexity analysis, a linear approach estimating the complexity of the trajectories of momentary EEG map series in state space. Compared to disbelievers, believers showed: more right-located sources of the beta2 band (18.5-21 Hz, excitatory activity); reduced interhemispheric differences in Omega complexity values; higher scores on the Magical Ideation scale; more general negative affect; and more hypnagogic-like reveries after a 4-min eyes-closed resting period. Thus, subjects differing in their declared paranormal belief displayed different active, cerebral neural populations during resting, task-free conditions. As hypothesized, believers showed relatively higher right hemispheric activation and reduced hemispheric asymmetry of functional complexity. These markers may constitute the neurophysiological basis for paranormal and schizotypal ideation.

Face-elicited ERPs and affective attitude: brain electric microstate and tomography analyses

Objectives: Although behavioral studies have demonstrated that normative affective traits modulate the processing of facial and emotionally charged stimuli, direct electrophysiological evidence for this modulation is still lacking. Methods: Event-related potential (ERP) data associated with personal, traitlike approach- or withdrawal-related attitude (assessed post-recording and 14 months later) were investigated in 18 subjects during task-free (i.e. unrequested, spontaneous) emotional evaluation of faces. Temporal and spatial aspects of 27 channel ERP were analyzed with microstate analysis and low resolution electromagnetic tomography (LORETA), a new method to compute 3 dimensional cortical current density implemented in the Talairach brain atlas. Results: Microstate analysis showed group differences 132-196 and 196-272 ms poststimulus, with right-shifted electric gravity centers for subjects with negative affective attitude. During these (over subjects reliably identifiable) personality-modulated, face-elicited microstates, LORETA revealed activation of bilateral occipito-temporal regions, reportedly associated with facial configuration extraction processes. Negative compared to positive affective attitude showed higher activity right temporal; positive compared to negative attitude showed higher activity left temporo-parieto-occipital. Conclusions: These temporal and spatial aspects suggest that the subject groups differed in brain activity at early, automatic, stimulus-related face processing steps when structural face encoding (configuration extraction) occurs. In sum, the brain functional microstates associated with affect-related personality features modulate brain mechanisms during face processing already at early information processing stages.

Effect of psychological interventions on depressive symptoms in long-term rehabilitation after an acquired brain injury: a systematic review and meta-analysis

OBJECTIVE To summarize empirical studies on the effectiveness of psychological interventions in long-term rehabilitation after an acquired brain injury (ABI) in reducing depressive symptoms. DATA SOURCES A systematic literature search was conducted on MEDLINE, PsycINFO, Embase, and CINAHL to identify articles published between January 1990 and October 2011. Search terms included the 3 concepts (1) "brain injur*" or "stroke," (2) "psychotherap*" or "therapy" or "intervention" or "rehabilitation," and (3) "depress*." STUDY SELECTION Studies evaluating psychological interventions in patients after ABI were included. Time since injury was on average more than 1 year. Trials reported data on validated depression questionnaires before and after the psychological intervention. DATA EXTRACTION Two independent reviewers extracted information from the sample, the intervention, and the outcome of the included studies and calculated effect sizes (ESs) from depression questionnaires. Thirteen studies were included in a pre-post analysis. Seven studies were eligible for a meta-analysis of ESs in active interventions and control conditions. DATA SYNTHESIS Pre-post ESs were significant in 4 of 13 studies. The overall ES of .69 (95% confidence interval [CI], .29-1.09) suggests a medium effectiveness of psychological interventions on depressive symptoms compared with control conditions. Moderator analysis of the number of sessions and adequate randomization procedure did not show significant ES differences between strata. Studies with adequate randomization did not, however, suggest the effectiveness of psychological interventions on depressive symptoms after ABI. CONCLUSIONS Psychological interventions are a promising treatment option for depressive symptoms in long-term rehabilitation after ABI. Since only a few adequately randomized controlled trials (RCTs) exist, more RCTs are required to confirm this initial finding.

A very rare cancer in Down syndrome: medulloblastoma. Epidemiological data from 13 countries

Persons with Down syndrome (DS) uniquely have an increased frequency of leukemias but a decreased total frequency of solid tumors. The distribution and frequency of specific types of brain tumors have never been studied in DS. We evaluated the frequency of primary neural cell embryonal tumors and gliomas in a large international data set. The observed number of children with DS having a medulloblastoma, central nervous system primitive neuroectodermal tumor (CNS-PNET) or glial tumor was compared to the expected number. Data were collected from cancer registries or brain tumor registries in 13 countries of Europe, America, Asia and Oceania. The number of DS children with each category of tumor was treated as a Poisson variable with mean equal to 0.000884 times the total number of registrations in that category. Among 8,043 neural cell embryonal tumors (6,882 medulloblastomas and 1,161 CNS-PNETs), only one patient with medulloblastoma had DS, while 7.11 children in total and 6.08 with medulloblastoma were expected to have DS. (p 0.016 and 0.0066 respectively). Among 13,797 children with glioma, 10 had DS, whereas 12.2 were expected. Children with DS appear to be specifically protected against primary neural cell embryonal tumors of the CNS, whereas gliomas occur at the same frequency as in the general population. A similar protection against neuroblastoma, the principal extracranial neural cell embryonal tumor, has been observed in children with DS. Additional genetic material on the supernumerary chromosome 21 may protect against embryonal neural cell tumor development.

The association between admission systolic blood pressure and mortality in significant traumatic brain injury: A multi-centre cohort study

INTRODUCTION Low systolic blood pressure (SBP) is an important secondary insult following traumatic brain injury (TBI), but its exact relationship with outcome is not well characterised. Although a SBP of <90mmHg represents the threshold for hypotension in consensus TBI treatment guidelines, recent studies suggest redefining hypotension at higher levels. This study therefore aimed to fully characterise the association between admission SBP and mortality to further inform resuscitation endpoints. METHODS We conducted a multicentre cohort study using data from the largest European trauma registry. Consecutive adult patients with AIS head scores >2 admitted directly to specialist neuroscience centres between 2005 and July 2012 were studied. Multilevel logistic regression models were developed to examine the association between admission SBP and 30 day inpatient mortality. Models were adjusted for confounders including age, severity of injury, and to account for differential quality of hospital care. RESULTS 5057 patients were included in complete case analyses. Admission SBP demonstrated a smooth u-shaped association with outcome in a bivariate analysis, with increasing mortality at both lower and higher values, and no evidence of any threshold effect. Adjusting for confounding slightly attenuated the association between mortality and SBP at levels <120mmHg, and abolished the relationship for higher SBP values. Case-mix adjusted odds of death were 1.5 times greater at <120mmHg, doubled at <100mmHg, tripled at <90mmHg, and six times greater at SBP<70mmHg, p<0.01. CONCLUSIONS These findings indicate that TBI studies should model SBP as a continuous variable and may suggest that current TBI treatment guidelines, using a cut-off for hypotension at SBP<90mmHg, should be reconsidered.

What is the incidence of intracranial bleeding in patients with mild traumatic brain injury? A retrospective study in 3088 Canadian CT head rule patients

OBJECTIVE Only limited data exists in terms of the incidence of intracranial bleeding (ICB) in patients with mild traumatic brain injury (MTBI). METHODS We retrospectively identified 3088 patients (mean age 41 range (7-99) years) presenting with isolated MTBI and GCS 14-15 at our Emergency Department who had undergone cranial CT (CCT) between 2002 and 2011. Indication for CCT was according to the "Canadian CT head rules." Patients with ICB were either submitted for neurosurgical treatment or kept under surveillance for at least 24 hours. Pearson's correlation coefficient was used to correlate the incidence of ICB with age, gender, or intake of coumarins, platelet aggregation inhibitors, or heparins. RESULTS 149 patients (4.8%) had ICB on CCT. No patient with ICB died or deteriorated neurologically. The incidence of ICB increased with age and intake of anticoagulants without clinically relevant correlation (R = 0.11; P < 0.001; R = -0.06; P < 0.001). CONCLUSION Our data show an incidence of 4.8% for ICB after MTBI. However, neurological deterioration after MTBI seems to be rare, and the need for neurosurgical intervention is only required in selected cases. The general need for CCT in patients after MTBI is therefore questionable, and clinical surveillance may be sufficient when CCT is not available.

Quantitative 1H-magnetic resonance spectroscopy of human brain: Influence of composition and parameterization of the basis set in linear combination model-fitting

Localized short-echo-time (1)H-MR spectra of human brain contain contributions of many low-molecular-weight metabolites and baseline contributions of macromolecules. Two approaches to model such spectra are compared and the data acquisition sequence, optimized for reproducibility, is presented. Modeling relies on prior knowledge constraints and linear combination of metabolite spectra. Investigated was what can be gained by basis parameterization, i.e., description of basis spectra as sums of parametric lineshapes. Effects of basis composition and addition of experimentally measured macromolecular baselines were investigated also. Both fitting methods yielded quantitatively similar values, model deviations, error estimates, and reproducibility in the evaluation of 64 spectra of human gray and white matter from 40 subjects. Major advantages of parameterized basis functions are the possibilities to evaluate fitting parameters separately, to treat subgroup spectra as independent moieties, and to incorporate deviations from straightforward metabolite models. It was found that most of the 22 basis metabolites used may provide meaningful data when comparing patient cohorts. In individual spectra, sums of closely related metabolites are often more meaningful. Inclusion of a macromolecular basis component leads to relatively small, but significantly different tissue content for most metabolites. It provides a means to quantitate baseline contributions that may contain crucial clinical information.

Hierarchical segmentation-assisted multimodal registration for MR brain images

Information theory-based metric such as mutual information (MI) is widely used as similarity measurement for multimodal registration. Nevertheless, this metric may lead to matching ambiguity for non-rigid registration. Moreover, maximization of MI alone does not necessarily produce an optimal solution. In this paper, we propose a segmentation-assisted similarity metric based on point-wise mutual information (PMI). This similarity metric, termed SPMI, enhances the registration accuracy by considering tissue classification probabilities as prior information, which is generated from an expectation maximization (EM) algorithm. Diffeomorphic demons is then adopted as the registration model and is optimized in a hierarchical framework (H-SPMI) based on different levels of anatomical structure as prior knowledge. The proposed method is evaluated using Brainweb synthetic data and clinical fMRI images. Both qualitative and quantitative assessment were performed as well as a sensitivity analysis to the segmentation error. Compared to the pure intensity-based approaches which only maximize mutual information, we show that the proposed algorithm provides significantly better accuracy on both synthetic and clinical data.

Characterization of the 9L gliosarcoma implanted in the Fischer rat: an orthotopic model for a grade IV brain tumor.

Among rodent models for brain tumors, the 9L gliosarcoma is one of the most widely used. Our 9L-European Synchrotron Radiation Facility (ESRF) model was developed from cells acquired at the Brookhaven National Laboratory (NY, USA) in 1997 and implanted in the right caudate nucleus of syngeneic Fisher rats. It has been largely used by the user community of the ESRF during the last decade, for imaging, radiotherapy, and chemotherapy, including innovative treatments based on particular irradiation techniques and/or use of new drugs. This work presents a detailed study of its characteristics, assessed by magnetic resonance imaging (MRI), histology, immunohistochemistry, and cytogenetic analysis. The data used for this work were from rats sampled in six experiments carried out over a 3-year period in our lab (total number of rats = 142). The 9L-ESRF tumors were induced by a stereotactic inoculation of 10(4) 9L cells in the right caudate nucleus of the brain. The assessment of vascular parameters was performed by MRI (blood volume fraction and vascular size index) and by immunostaining of vessels (rat endothelial cell antigen-1 and type IV collagen). Immunohistochemistry and regular histology were used to describe features such as tumor cell infiltration, necrosis area, nuclear pleomorphism, cellularity, mitotic characteristics, leukocytic infiltration, proliferation, and inflammation. Moreover, for each of the six experiments, the survival of the animals was assessed and related to the tumor growth observed by MRI or histology. Additionally, the cytogenetic status of the 9L cells used at ESRF lab was investigated by comparative genomics hybridization analysis. Finally, the response of the 9L-ESRF tumor to radiotherapy was estimated by plotting the survival curves after irradiation. The median survival time of 9L-ESRF tumor-bearing rats was highly reproducible (19-20 days). The 9L-ESRF tumors presented a quasi-exponential growth, were highly vascularized with a high cellular density and a high proliferative index, accompanied by signs of inflammatory responses. We also report an infiltrative pattern which is poorly observed on conventional 9 L tumor. The 9L-ESRF cells presented some cytogenetic specificities such as altered regions including CDK4, CDKN2A, CDKN2B, and MDM2 genes. Finally, the lifespan of 9L-ESRF tumor-bearing rats was enhanced up to 28, 35, and 45 days for single doses of 10, 20, and 2 × 20 Gy, respectively. First, this report describes an animal model that is used worldwide. Second, we describe few features typical of our model if compared to other 9L models worldwide. Altogether, the 9L-ESRF tumor model presents characteristics close to the human high-grade gliomas such as high proliferative capability, high vascularization and a high infiltrative pattern. Its response to radiotherapy demonstrates its potential as a tool for innovative radiotherapy protocols.

Atopic conditions and brain tumor risk in children and adolescents--an international case-control study (CEFALO)

BACKGROUND A number of epidemiological studies indicate an inverse association between atopy and brain tumors in adults, particularly gliomas. We investigated the association between atopic disorders and intracranial brain tumors in children and adolescents, using international collaborative CEFALO data. PATIENTS AND METHODS CEFALO is a population-based case-control study conducted in Denmark, Norway, Sweden, and Switzerland, including all children and adolescents in the age range 7-19 years diagnosed with a primary brain tumor between 2004 and 2008. Two controls per case were randomly selected from population registers matched on age, sex, and geographic region. Information about atopic conditions and potential confounders was collected through personal interviews. RESULTS In total, 352 cases (83%) and 646 controls (71%) participated in the study. For all brain tumors combined, there was no association between ever having had an atopic disorder and brain tumor risk [odds ratio 1.03; 95% confidence interval (CI) 0.70-1.34]. The OR was 0.76 (95% CI 0.53-1.11) for a current atopic condition (in the year before diagnosis) and 1.22 (95% CI 0.86-1.74) for an atopic condition in the past. Similar results were observed for glioma. CONCLUSIONS There was no association between atopic conditions and risk of all brain tumors combined or of glioma in particular. Stratification on current or past atopic conditions suggested the possibility of reverse causality, but may also the result of random variation because of small numbers in subgroups. In addition, an ongoing tumor treatment may affect the manifestation of atopic conditions, which could possibly affect recall when reporting about a history of atopic diseases. Only a few studies on atopic conditions and pediatric brain tumors are currently available, and the evidence is conflicting.

Blocking brain-derived neurotrophic factor inhibits injury-induced hyperexcitability of hippocampal CA3 neurons

Brain trauma can disrupt synaptic connections, and this in turn can prompt axons to sprout and form new connections. If these new axonal connections are aberrant, hyperexcitability can result. It has been shown that ablating tropomyosin-related kinase B (TrkB), a receptor for brain-derived neurotrophic factor (BDNF), can reduce axonal sprouting after hippocampal injury. However, it is unknown whether inhibiting BDNF-mediated axonal sprouting will reduce hyperexcitability. Given this, our purpose here was to determine whether pharmacologically blocking BDNF inhibits hyperexcitability after injury-induced axonal sprouting in the hippocampus. To induce injury, we made Schaffer collateral lesions in organotypic hippocampal slice cultures. As reported by others, we observed a 50% reduction in axonal sprouting in cultures treated with a BDNF blocker (TrkB-Fc) 14 days after injury. Furthermore, lesioned cultures treated with TrkB-Fc were less hyperexcitable than lesioned untreated cultures. Using electrophysiology, we observed a two-fold decrease in the number of CA3 neurons that showed bursting responses after lesion with TrkB-Fc treatment, whereas we found no change in intrinsic neuronal firing properties. Finally, evoked field excitatory postsynaptic potential recordings indicated an increase in network activity within area CA3 after lesion, which was prevented with chronic TrkB-Fc treatment. Taken together, our results demonstrate that blocking BDNF attenuates injury-induced hyperexcitability of hippocampal CA3 neurons. Axonal sprouting has been found in patients with post-traumatic epilepsy. Therefore, our data suggest that blocking the BDNF-TrkB signaling cascade shortly after injury may be a potential therapeutic target for the treatment of post-traumatic epilepsy.

Nocardial brain abscess: observation of treatment strategies and outcome in Switzerland from 1992 to 1999

BACKGROUND Brain abscesses caused by Nocardia spp. are rare, but life-threatening infections that are notoriously difficult to diagnose and treat and which occur mainly in immunocompromised patients. Standard treatment guidelines are not available. METHODS A systematic search for nocardial brain abscesses from 1992 to 1999 was conducted in Switzerland for the comparison of clinical presentation, treatment strategies and outcome. RESULTS Seven cases were found, for which data of six were available. In 4/6 patients antimicrobial therapy led to a decrease in the size of abscesses. Four of six patients died. The cause of death was likely due to underlying co-morbidities, rather than the nocardial infection. CONCLUSION The finding that treatment was different in each case underscores the lack of therapeutic guidelines.

PCR identification of HIV-1 DNA sequences in brain tissue of patients with AIDS encephalopathy.

We analyzed brain tissue from 39 patients for the presence of proviral HIV-1 sequences, using the polymerase chain reaction (PCR) for the amplification of segments of the viral LTR and gag genes. A novel primer extension procedure allowed the detection of a single HIV-1 copy in 1 micrograms DNA. We detected proviral HIV-1 DNA in 16 of 25 brain samples from AIDS patients. Semiquantitative evaluation of the amplified DNAs indicated considerable variation in viral load. Highest levels of proviral DNA were present in brain samples from six patients with clinical evidence of HIV-associated cognitive/motor complex and the histopathologic correlate of HIV leukoencephalopathy or HIV encephalitis. An additional 11 brain samples contained smaller amounts of proviral DNA. In these patients, clinical data were inconclusive regarding the diagnosis of HIV-1 encephalopathy and histopathologically there was no evidence of HIV-1-induced tissue lesions. In nine of 25 seropositive patients with AIDS (36%), brain samples scored negative or did not contain an unequivocal signal indicating the presence of proviral DNA. HIV-1 sequences were not detected in any of 14 control brain samples from HIV-1 seronegative patients. Our data indicate that HIV-1 is present in the central nervous system of the majority (two thirds) of AIDS patients and that the highest levels of proviral DNA in brain tissue are associated with HIV encephalopathy.

Patient-Specific Semi-Supervised Learning for Postoperative Brain Tumor Segmentation

In contrast to preoperative brain tumor segmentation, the problem of postoperative brain tumor segmentation has been rarely approached so far. We present a fully-automatic segmentation method using multimodal magnetic resonance image data and patient-specific semi-supervised learning. The idea behind our semi-supervised approach is to effectively fuse information from both pre- and postoperative image data of the same patient to improve segmentation of the postoperative image. We pose image segmentation as a classification problem and solve it by adopting a semi-supervised decision forest. The method is evaluated on a cohort of 10 high-grade glioma patients, with segmentation performance and computation time comparable or superior to a state-of-the-art brain tumor segmentation method. Moreover, our results confirm that the inclusion of preoperative MR images lead to a better performance regarding postoperative brain tumor segmentation.