Real-Time fMRI Pattern Decoding and Neurofeedback Using FRIEND: An FSL-Integrated BCI Toolbox

The demonstration that humans can learn to modulate their own brain activity based on feedback of neurophysiological signals opened up exciting opportunities for fundamental and applied neuroscience. Although EEG-based neurofeedback has been long employed both in experimental and clinical investigation, functional MRI (fMRI)-based neurofeedback emerged as a promising method, given its superior spatial resolution and ability to gauge deep cortical and subcortical brain regions. In combination with improved computational approaches, such as pattern recognition analysis (e.g., Support Vector Machines, SVM), fMRI neurofeedback and brain decoding represent key innovations in the field of neuromodulation and functional plasticity. Expansion in this field and its applications critically depend on the existence of freely available, integrated and user-friendly tools for the neuroimaging research community. Here, we introduce FRIEND, a graphic-oriented user-friendly interface package for fMRI neurofeedback and real-time multivoxel pattern decoding. The package integrates routines for image preprocessing in real-time, ROI-based feedback (single-ROI BOLD level and functional connectivity) and brain decoding-based feedback using SVM. FRIEND delivers an intuitive graphic interface with flexible processing pipelines involving optimized procedures embedding widely validated packages, such as FSL and libSVM. In addition, a user-defined visual neurofeedback module allows users to easily design and run fMRI neurofeedback experiments using ROI-based or multivariate classification approaches. FRIEND is open-source and free for non-commercial use. Processing tutorials and extensive documentation are available.     

Implicaciones de los síntomas depresivos en los ancianos hospitalizados por afección médica

Introduction

Depressive symptoms in hospitalized patients are very common, and they have been related to higher mortality. The aim of the study was to estimate the prevalence of depressive symptoms in hospitalized elderly patients and its relationship to various diseases, as well as their functional and mental status and mortality.

Material and methods

A total of 115 patients over 64 years of age were prospectively studied. The validated Spanish version of the Geriatric Depression Scale of Yesavage (15-item version) was used. Patients were considered to have depressive symptoms if ≥6 points were obtained. The demographic characteristics, the Charlson comorbidity index, the diagnosis at admission, the functional status assessed by the Barthel and Lawton-Brodie index, the mental capacity assessed by the Pfeiffer questionnaire, the length of the hospital stay, and hospital mortality were recorded.

Results

Out of the 115 patients studied, with a mean age of 70.5 years, 71 (61.7%) were female. Depressive symptoms were observed in 46 patients (40%, 95% CI: 34.8-43.9). Patients who died showed a significantly higher score on the Yesavage scale (P=.04). The multivariate analysis showed a significantly independent association between depressive symptoms and functional capacity (P=.026), mental status (P=.021), renal failure (P=.001), liver disease (P=.018), and osteoarthritis (P=.017), but losing the previously seen significant association with diabetes (P=.43).

Conclusions

The prevalence of depressive symptoms in hospitalized elderly patients is high, and is associated with the diagnoses of renal failure, liver disease and osteoarthritis, with a higher comorbidity and especially with a poorer functional capacity.     

Nitrate and nitrite removal from salted water by Haloferax mediterranei

Haloferax mediterranei is a denitrifying halophilic archaeon, able to assimilate nitrate or nitrite in the presence of oxygen by the assimilatory nitrate pathway. It can also grow in the presence of high nitrate or nitrite concentrations under anoxic conditions, using both nitrogen species as electron acceptors. In this study, the ability of H. mediterranei to remove high nitrate and nitrite concentrations from culture media has been demonstrated. This suggests that this haloarchaeon could be applied in water bioremediation processes to repair damage caused by anthropogenic activities. This could be beneficial in regions such as Comunidad Valenciana or Murcia (Spain), where the water tables contain high nitrate and nitrite concentrations due to fertiliser addition, and high salt concentrations due to marine intrusions.     

Genetic polymorphisms of NAT2, CYP2E1 and GST enzymes and the occurrence of antituberculosis drug-induced hepatitis in Brazilian TB patients

Isoniazid (INH), one of the most important drugs used in antituberculosis (anti-TB) treatment, is also the major drug involved in hepatotoxicity. Differences in INH-induced toxicity have been attributed to genetic variability at several loci, such as NAT2, CYP2E1, GSTM1 and GSTT1, that code for drug-metabolising enzymes. Our goal was to examine the polymorphisms in these enzymes as susceptibility factors to anti-TB drug-induced hepatitis in Brazilian individuals. In a case-control design, 167 unrelated active tuberculosis patients from the University Hospital of the Federal University of Rio de Janeiro, Brazil, were enrolled in this study. Patients with a history of anti-TB drug-induced acute hepatitis (cases with an increase to 3 times the upper limit of normal serum transaminases and symptoms of hepatitis) and patients with no evidence of anti-TB hepatic side effects (controls) were genotyped for NAT2, CYP2E1, GSTM1 and GSTT1 polymorphisms. Slow acetylators had a higher incidence of hepatitis than intermediate/rapid acetylators [22% (18/82) vs. 9.8% (6/61), odds ratio (OR), 2.86, 95% confidence interval (CI), 1.06-7.68, p = 0.04). Logistic regression showed that slow acetylation status was the only independent risk factor (OR 3.59, 95% CI, 2.53-4.64, p = 0.02) for the occurrence of anti-TB drug-induced hepatitis during anti-TB treatment with INH-containing schemes in Brazilian individuals.     

Voluntary Enhancement of Neural Signatures of Affiliative Emotion Using fMRI Neurofeedback

In Ridley Scott’s film “Blade Runner”, empathy-detection devices are employed to measure affiliative emotions. Despite recent neurocomputational advances, it is unknown whether brain signatures of affiliative emotions, such as tenderness/affection, can be decoded and voluntarily modulated. Here, we employed multivariate voxel pattern analysis and real-time fMRI to address this question. We found that participants were able to use visual feedback based on decoded fMRI patterns as a neurofeedback signal to increase brain activation characteristic of tenderness/affection relative to pride, an equally complex control emotion. Such improvement was not observed in a control group performing the same fMRI task without neurofeedback. Furthermore, the neurofeedback-driven enhancement of tenderness/affection-related distributed patterns was associated with local fMRI responses in the septohypothalamic area and frontopolar cortex, regions previously implicated in affiliative emotion. This demonstrates that humans can voluntarily enhance brain signatures of tenderness/affection, unlocking new possibilities for promoting prosocial emotions and countering antisocial behavior.     

Antimicrobial activity of ergokonin A from Trichoderma longibrachiatum

AIMS: Natural fungal products were screened for antifungal compounds. The mode of action of one of the hits found and the taxonomy of the producing organism were analysed. METHODS AND RESULTS: An extract from a Trichoderma species showed a more potent activity in an agar-based assay against the null mutant fks1::HIS strain than against the wild-type strain, suggesting that it could contain a glucan synthesis inhibitor. The active component was identified as the known compound ergokonin A. The compound exhibited activity against Candida and Aspergillus species, but was inactive against Cryptococcus species. It induced alterations in the hyphal morphology of Aspergillus fumigatus. The identification of the producing isolate was confirmed by sequencing of the rDNA internal transcribed spacers and comparison with the sequences of other Trichoderma species. The analysis showed that the producing fungus had a high homology with other strains classified as Trichoderma longibrachiatum and its teleomorph Hypocrea schweinitzii. CONCLUSIONS: The antifungal activity spectrum of ergokonin A and the morphology alterations induced on A. fumigatus are consistent with glucan synthesis as the target for ergokonin A. The production of ergokonin A is not uncommon, but is probably restricted to Trichoderma species. SIGNIFICANCE AND IMPACT OF THE STUDY: The discovery that ergokonin A could be an inhibitor of glucan synthesis, having a structure very different to other inhibitors, increases the likelihood that orally active agents with this fungal-specific mode of action may be developed.     

Patterns of antimicrobial activities from soil actinomycetes isolated under different conditions of pH and salinity

AIMS: To evaluate the patterns of the production of antimicrobial compounds by diverse collection of actinomycetes isolated from different geographies under alternative conditions of pH and salinity in the media. METHODS AND RESULTS: Actinomycetes were grouped based on their method of isolation and their phenotype diversity was determined by total fatty acid analysis. A total of 335 representative isolates, including 235 Streptomyces species and 100 actinomycetes from other taxa, were screened for the production of antimicrobial activities against a panel of bacteria, filamentous fungi and yeasts, including some of clinical relevance. Production of antimicrobial activities was detected in 230 strains. In the case of the genus Streptomyces, 181 antimicrobial activities (77% of the tested isolates) were recorded. The activities observed among the other actinomycetes taxa were lower (49% of the tested isolates). CONCLUSIONS: The results of this study support the idea that species of actinomycetes isolated in alternative selective conditions of pH and salinity present a significant capacity to produce compounds with antibacterial or antifungal activity. The best group of isolates in terms of production of active secondary metabolites was the one isolated in saline conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: The results demonstrate that these actinomycetes strains isolated in alternative selective conditions of pH and salinity and collected from diverse geographical locations present a significant capacity to produce compounds with antibacterial or antifungal activity.     

The discovery of enfumafungin, a novel antifungal compound produced by an endophytic Hormonema species biological activity and taxonomy of the producing organisms

In a screening of natural products with antifungal activity derived from endophytic fungi, we detected a potent activity in a culture belonging to the form-genus Hormonema, isolated from leaves of Juniperus communis. The compound is a new triterpene glycoside, showing an antifungal activity highly potent in vitro against Candida and Aspergillus and with moderate efficacy in an in vivo mouse model of disseminated candidiasis. The agent is especially interesting since its antifungal spectrum and its effect on morphology of Aspergillus fumigatus is comparable to that of the glucan synthase inhibitor pneumocandin B,,, the natural precursor of the clinical candidate MK-0991 (caspofungin acetate). An additional search for other Hormonema isolates producing improved titers or derivatives resulted in the isolation of two more strains recovered from the same plant host showing identical activity. The producing isolates were compared with other non-producing Hormonema strains by DNA fingerprinting and sequencing of the rDNA internal transcribed spacers. Comparison of rDNA sequences with other fungal species suggests that the producing fungus could be an undetermined Kabatina species. Kabatina is a coelomycetous genus whose members are known to produce Hormonema-like states in culture.     

First larval record of Mesocestoides in carnivora of Tenerife (Canary Islands)

Larvae of Mesocestoides sp. were recovered in Tenerife (Canary Islands) in 2004 from the peritoneal cavities of 2 domestic dogs and a domestic cat. Morphological and molecular identification were carried out. Mesocestoides litteratus from Vulpes vulpes was sequenced for the first time using the ITS-2 region (18S rDNA), and was included in the phylogenetic analysis to compare the sequence variability among these and other Mesocestoides spp. belonging to different carnivores. Phylogenetic studies were carried out based on maximum parsimony and neighbor-joining analysis. The results showed the relationships between these and other previously published Mesocestoides species. Moreover, it is demonstrated that Mesocestoides sp. from Tenerife comprises a previously unreported sequence. This is the first larval record of Mesocestoides sp. in domestic animals from Tenerife, Canary Islands, Spain.