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Background The EXPLORE (Evaluating Xience and Left Ventricular Function in PCI on Occlusions After STEMI) trial was the first and only randomized trial investigating chronic total occlusion (CTO) percutaneous coronary intervention (PCI) early after primary PCI for ST‐segment–elevation myocardial infarction, compared with medical therapy for the CTO. We performed a 10‐year follow‐up of EXPLORE to investigate long‐term safety and clinical impact of CTO PCI after ST‐segment–elevation myocardial infarction, compared with no‐CTO PCI. Methods and Results In EXPLORE, 302 patients post‐ST‐segment–elevation myocardial infarction with concurrent CTO were randomized to CTO PCI within ≈1 week or no‐CTO PCI. We performed an extended clinical follow‐up for the primary end point of major adverse cardiac events, consisting of cardiovascular death, coronary artery bypass grafting, or myocardial infarction. Secondary end points included all‐cause death, angina, and dyspnea. Median follow‐up was 10 years (interquartile range, 8–11 years). The primary end point occurred in 25% of patients with CTO PCI and in 24% of patients with no‐CTO PCI (hazard ratio [HR], 1.11 [95% CI, 0.70–1.76]). Cardiovascular mortality was higher in the CTO PCI group (HR, 2.09 [95% CI, 1.10–2.50]), but all‐cause death was similar (HR, 1.53 [95% CI, 0.93–2.50]). Dyspnea relief was more frequent after CTO PCI (83% versus 65%, P=0.005), with no significant difference in angina. Conclusions This 10‐year follow‐up of patients post‐ST‐segment–elevation myocardial infarction randomized to CTO PCI or no‐CTO PCI demonstrated no clinical benefit of CTO PCI in major adverse cardiac events or overall mortality. However, CTO PCI was associated with a higher cardiovascular mortality compared with no‐CTO PCI. Our long‐term data support a careful weighing of effective symptom relief against an elevated cardiovascular mortality risk in CTO PCI decisions. Registration URL: https://www.trialregister.nl; Unique identifier: NTR1108.

Immobilisation and anaesthesia of wild felids may be complex and potentially dangerous events, making it difficult to implement more advanced anaesthetic techniques such as neuraxial anaesthesia. A Eurasian lynx was referred for femur fracture repair after it was seen with lameness of the left pelvic limb sustained in its natural environment. The animal was remotely darted using a combination of ketamine (5 mg/kg) and xylazine (5 mg/kg) intramuscularly. Once immobilised, the lynx was transported to the veterinary hospital in a restraining cage. After induction and endotracheal intubation, pelvic limb radiographs confirmed a closed, comminuted fracture of the left femur that required open reduction and internal stabilisation. A sacrococcygeal epidural was performed before surgery using lidocaine (2 mg/kg) and morphine (0.1 mg/kg) to complement the ketamine–xylazine–isoflurane anaesthesia, which allows a low-end-tidal isoflurane concentration. Clinical signs were continuously monitored and remained stable during the entire procedure, with the exception of a temperature that decreased to 35.8°C. No intraoperative analgesic rescues were necessary. Recovery was smooth and uneventful. The lynx showed no signs of motor weakness after surgery or other side effects related to the anaesthetic procedure. The successful management of this surgical case suggests that the described anaesthetic protocol could be recommended in orthopaedic procedures of the pelvic limbs in wild Felidae.

Dual-tasking is extremely prominent nowadays, despite ample evidence that it comes with a performance cost: the Dual-Task (DT) cost. Neuroimaging studies have established that tasks are more likely to interfere if they rely on common brain regions, but the precise neural origin of the DT cost has proven elusive so far, mostly because fMRI does not record neural activity directly and cannot reveal the key effect of timing, and how the spatio-temporal neural dynamics of the tasks coincide. Recently, DT electrophysiological studies in monkeys have recorded neural populations shared by the two tasks with millisecond precision to provide a much finer understanding of the origin of the DT cost. We used a similar approach in humans, with intracranial EEG, to assess the neural origin of the DT cost in a particularly challenging naturalistic paradigm which required accurate motor responses to frequent visual stimuli (task T1) and the retrieval of information from long-term memory (task T2), as when answering passengers’ questions while driving. We found that T2 elicited neuroelectric interferences in the gamma-band (>40 Hz), in key regions of the T1 network including the Multiple Demand Network. They reproduced the effect of disruptive electrocortical stimulations to create a situation of dynamical incompatibility, which might explain the DT cost. Yet, participants were able to flexibly adapt their strategy to minimize interference, and most surprisingly, reduce the reliance of T1 on key regions of the executive control network-the anterior insula and the dorsal anterior cingulate cortex-with no performance decrement.

We here turn the general and theoretical question of the complementarity of EEG and MEG for source reconstruction, into a practical empirical one. Precisely, we address the challenge of evaluating multimodal data fusion on real data. For this purpose, we build on the flexibility of Parametric Empirical Bayes, namely for EEG-MEG data fusion, group level inference and formal hypothesis testing.The proposed approach follows a two-step procedure by first using unimodal or multimodal inference to derive a cortical solution at the group level; and second by using this solution as a prior model for single subject level inference based on either unimodal or multimodal data. Interestingly, for inference based on the same data (EEG, MEG or both), one can then formally compare, as alternative hypotheses, the relative plausibility of the two unimodal and the multimodal group priors. Using auditory data, we show that this approach enables to draw important conclusions, namely on (i) the superiority of multimodal inference, (ii) the greater spatial sensitivity of MEG compared to EEG, (iii) the ability of EEG data alone to source reconstruct temporal lobe activity, (iv) the usefulness of EEG to improve MEG based source reconstruction.Importantly, we largely reproduce those findings over two different experimental conditions. We here focused on Mismatch Negativity (MMN) responses for which generators have been extensively investigated with little homogeneity in the reported results. Our multimodal inference at the group level revealed spatio-temporal activity within the supratemporal plane with a precision which, to our knowledge, has never been achieved before with non-invasive recordings.

Antigen binding by antibodies requires precise orientation of the complementarity- determining region (CDR) loops in the variable domain to establish the correct contact surface. Members of the family Camelidae have a modified form of immunoglobulin gamma (IgG) with only heavy chains, called Heavy Chain only Antibodies (HCAb). Antigen binding in HCAbs is mediated by only three CDR loops from the single variable domain (VHH) at the N-terminus of each heavy chain. This feature of the VHH, along with their other important features, e.g., easy expression, small size, thermo-stability and hydrophilicity, made them promising candidates for therapeutics and diagnostics. Thus, to design better VHH domains, it is important to thoroughly understand their sequence and structure characteristics and relationship. In this study, sequence characteristics of VHH domains have been analysed in depth, along with their structural features using innovative approaches, namely a structural alphabet. An elaborate summary of various studies proposing structural models of VHH domains showed diversity in the algorithms used. Finally, a case study to elucidate the differences in structural models from single and multiple templates is presented. In this case study, along with the above-mentioned aspects of VHH, an exciting view of various factors in structure prediction of VHH, like template framework selection, is also discussed.

Attention operates through top-down (TD) and bottom-up (BU) mechanisms. Recently, it has been shown that slow (alpha) frequencies index facilitatory and suppressive mechanisms of TD attention and faster (gamma) frequencies signal BU attentional capture. Ageing is characterized by increased behavioral distractibility, resulting from either a reduced efficiency of TD attention or an enhanced triggering of BU attention. However, only few studies have investigated the impact of ageing upon the oscillatory activities involved in TD and BU attention. MEG data were collected from 14 elderly and 14 matched young healthy human participants while performing the Competitive Attention Task. Elderly participants displayed (1) exacerbated behavioral distractibility, (2) altered TD suppressive mechanisms, indexed by a reduced alpha synchronization in task-irrelevant regions, (3) less prominent alpha peak-frequency differences between cortical regions, (4) a similar BU system activation indexed by gamma activity, and (5) a reduced activation of lateral prefrontal inhibitory control regions. These results show that the ageing-related increased distractibility is of TD origin.

Magnetoencephalography (MEG) is a useful non-invasive technique for presurgical evaluation of focal cortical dysplasia patients. We aimed at clarifying the precise spatial relationship between the spiking volume determined with MEG, the seizure onset zone and the lesional volume in patients with focal cortical dysplasia.We studied the spatial relationships between the MEG spiking volume determined with a recent analysis pipeline, the seizure-onset zone location determined with a quantitative index calculated from intracranial EEG signals (‘Epileptogenicity Index’) and the lesional volume delineated on brain MRI in 11 patients with Focal Cortical Dysplasia explored with Stereo-electroencephalography (SEEG).A significant correlation between the MEG spiking activity and the Epileptogenicity Index was found in 8/11 patients. 7/8 patients were operated upon and had good surgical outcome. For three patients, no correlation between Epileptogenicity Index and spiking activity was observed; only one of those three patients had good surgical outcome.The lesion was at least partially overlapping with the seizure-onset zone in 8/9 patients with a lesion clearly identifiable by MRI. However, 57% of the SEEG epileptogenic contacts were located outside of the lesional volume. Lastly 44% of the highly epileptogenic SEEG contacts were located within the spiking volume and 22% of them were located exclusively in the spiking volume and not in the lesion. For 7/9 patients with a lesion,

The spatiotemporal structure of wind-driven circulation patterns and associated water exchanges can drive important bio-hydrodynamic interactions in shallow lagoons. The Vaccarès lagoon system is a complex shallow hydrosystem located in the central part of the Rhône Delta (France). It is internationally recognized as part of a biosphere reserve within the framework of UNESCO’s Man and Biosphere Programme, and as a RAMSAR site. Due to its frequent occurrence in this area, and considering the shallowness of the Vaccarès lagoon system, wind is assumed to play a major role in the hydrodynamic and biological processes. In this study, a hydrodynamic model was developed to investigate the structure of wind-driven circulations in the Vaccarès lagoon system, to provide insights into their role in transport and water exchange processes. The implementation and assessment (calibration and validation) of the model is presented first. Simulations were then performed for two typical steady wind conditions and for one measured unsteady wind event. The results illustrate the influence of the complex geometry of the Vaccarès lagoon system on the wind-driven circulations, and the differences observed between the different sub-lagoons in this system. The differences in wind-induced water exchanges between these sub-lagoons are also discussed.

Brain-computer interfaces (BCIs) mostly rely on electrophysiological brain signals. Methodological and technical progress has largely solved the challenge of processing these signals online. The main issue that remains, however, is the identification of a reliable mapping between electrophysiological measures and relevant states of mind. This is why BCIs are highly dependent upon advances in cognitive neuroscience and neuroimaging research. Recently, psychological theories became more biologically plausible, leading to more realistic generative models of psychophysiological observations. Such complex interpretations of empirical data call for efficient and robust computational approaches that can deal with statistical model comparison, such as approximate Bayesian inference schemes. Importantly, the latter enable the optimization of a model selection error rate with respect to experimental control variables, yielding maximally powerful designs. In this paper, we use a Bayesian decision theoretic approach to cast model comparison in an online adaptive design optimization procedure. We show how to maximize design efficiency for individual healthy subjects or patients. Using simulated data, we demonstrate the face- and construct-validity of this approach and illustrate its extension to electrophysiology and multiple hypothesis testing based on recent psychophysiological models of perception. Finally, we discuss its implications for basic neuroscience and BCI itself.

The emerging single-cell RNA-Seq (scRNA-Seq) technology holds the promise to revolutionize our understanding of diseases and associated biological processes at an unprecedented resolution. It opens the door to reveal the intercellular heterogeneity and has been employed to a variety of applications, ranging from characterizing cancer cells subpopulations to elucidating tumor resistance mechanisms. Parallel to improving experimental protocols to deal with technological issues, deriving new analytical methods to reveal the complexity in scRNA-Seq data is just as challenging. Here we review the current state-of-the-art bioinformatics tools and methods for scRNA-Seq analysis, as well as addressing some critical analytical challenges that the field faces.

Our understanding of the brain's functional organisation has greatly benefited from occasional exploratory sessions during electrophysiological studies, trying various manipulations of an animal's environment to trigger responses in particular neurons. Famous examples of such exploration have unveiled various unexpected response properties, such as those of mirror neurons. This approach, which relies on the possibility to test online the reactivity of precise neural populations has no equivalent so far in humans. The present study proposes and applies a radically novel framework for mapping human brain functions in ecological situations based on a combination of a) exploratory sessions, using real-time electrophysiology to formulate hypotheses about the functional role of precise cortical regions and b) controlled experimental protocols specifically adapted to test these hypotheses. Using this two-stage approach with an epileptic patient candidate for surgery and implanted with intracerebral electrodes, we were able to precisely map high-level auditory functions in the patients' superior temporal lobe. We propose that this procedure constitutes at the least a useful complement of electrical cortical stimulations to map eloquent brain areas in epileptic patients before their surgery, but also a path of discovery for human functional brain mapping

Duffy Antigen Receptor for Chemokines (DARC) plays multiple roles in human health as a blood group antigen, a receptor for chemokines and the only known receptor for Plasmodium vivax merozoites. It is the target of the murine anti-Fy6 monoclonal antibody 2C3 which binds to the first extracellular domain (ECD1), but exact nature of the recognized epitope was a subject of contradictory reports. Here, using a set of complex experiments which include expression of DARC with amino acid substitutions within the Fy6 epitope in E. coli and K562 cells, ELISA, surface plasmon resonance (SPR) and flow cytometry, we have resolved discrepancies between previously published reports and show that the basic epitope recognized by 2C3 antibody is 22FEDVW26, with 22F and 26W being the most important residues. In addition, we demonstrated that 30Y plays an auxiliary role in binding, particularly when the residue is sulfated. The STD-NMR studies performed using 2C3-derived Fab and synthetic peptide corroborated most of these results, and together with the molecular modelling suggested that 25V is not involved in direct interactions with the antibody, but determines folding of the epitope backbone.

We aimed at better understanding the brain mechanisms involved in the processing of alerting meaningful sounds during sleep, investigating alpha activity. During EEG acquisition, subjects were presented with a passive auditory oddball paradigm including rare complex sounds called Novels (the own first name - OWN, and an unfamiliar first name - OTHER) while they were watching a silent movie in the evening or sleeping at night. During the experimental night, the subjects' quality of sleep was generally preserved. During wakefulness, the decrease in alpha power (8-12 Hz) induced by Novels was significantly larger for OWN than for OTHER at parietal electrodes, between 600 and 900 ms after stimulus onset. Conversely, during REM sleep, Novels induced an increase in alpha power (from 0 to 1200 ms at all electrodes), significantly larger for OWN than for OTHER at several parietal electrodes between 700 and 1200 ms after stimulus onset. These results show that complex sounds have a different effect on the alpha power during wakefulness (decrease) and during REM sleep (increase) and that OWN induce a specific effect in these two states. The increased alpha power induced by Novels during REM sleep may 1) correspond to a short and transient increase in arousal; in this case, our study provides an objective measure of the greater arousing power of OWN over OTHER, 2) indicate a cortical inhibition associated with sleep protection. These results suggest that alpha modulation could participate in the selection of stimuli to be further processed during sleep.

BACKGROUND:The transition from enucleated reticulocytes to mature normocytes is marked by substantial remodeling of the erythrocytic cytoplasm and membrane. Despite conspicuous changes, most studies describe the maturing reticulocyte as a homogenous erythropoietic cell type. While reticulocyte staging based on fluorescent RNA stains such as thiazole orange have been useful in a clinical setting; these 'sub-vital' stains may confound delicate studies on reticulocyte biology and may preclude their use in heamoparasite invasion studies. DESIGN AND METHODS:Here we use highly purified populations of reticulocytes isolated from cord blood, sorted by flow cytometry into four sequential subpopulations based on transferrin receptor (CD71) expression: CD71high, CD71medium, CD71low and CD71negative. Each of these subgroups was phenotyped in terms of their, morphology, membrane antigens, biomechanical properties and metabolomic profile. RESULTS:Superficially CD71high and CD71medium reticulocytes share a similar gross morphology (large and multilobular) when compared to the smaller, smooth and increasingly concave reticulocytes as seen in the in the CD71low and CD71negativesamples. However, between each of the four sample sets we observe significant decreases in shear modulus, cytoadhesive capacity, erythroid receptor expression (CD44, CD55, CD147, CD235R, and CD242) and metabolite concentrations. Interestingly increasing amounts of boric acid was found in the mature reticulocytes. CONCLUSIONS:Reticulocyte maturation is a dynamic and continuous process, confounding efforts to rigidly classify them. Certainly this study does not offer an alternative classification strategy; instead we used a nondestructive sampling method to examine key phenotypic changes of in reticulocytes. Our study emphasizes a need to focus greater attention on reticulocyte biology.

The ABO blood group influences susceptibility to severe Plasmodium falciparum malaria. Recent evidence indicates that the protective effect of group O operates by virtue of reduced rosetting of infected red blood cells (iRBCs) with uninfected RBCs. Rosetting is mediated by a subgroup of PfEMP1 adhesins, with RBC binding being assigned to the N-terminal DBL1α₁ domain. Here, we identify the ABO blood group as the main receptor for VarO rosetting, with a marked preference for group A over group B, which in turn is preferred to group O RBCs. We show that recombinant NTS-DBL1α₁ and NTS-DBL1α₁-CIDR1γ reproduce the VarO-iRBC blood group preference and document direct binding to blood group trisaccharides by surface plasmon resonance. More detailed RBC subgroup analysis showed preferred binding to group A₁, weaker binding to groups A₂ and B, and least binding to groups A(x) and O. The 2.8 Å resolution crystal structure of the PfEMP1-VarO Head region, NTS-DBL1α₁-CIDR1γ, reveals extensive contacts between the DBL1α₁ and CIDR1γ and shows that the NTS-DBL1α₁ hinge region is essential for RBC binding. Computer docking of the blood group trisaccharides and subsequent site-directed mutagenesis localized the RBC-binding site to the face opposite to the heparin-binding site of NTS-DBLα₁. RBC binding involves residues that are conserved between rosette-forming PfEMP1 adhesins, opening novel opportunities for intervention against severe malaria. By deciphering the structural basis of blood group preferences in rosetting, we provide a link between ABO blood grouppolymorphisms and rosette-forming adhesins, consistent with the selective role of falciparum malaria on human genetic makeup.

We present a brain-computer interface (BCI) version of the famous “Connect Four”. Target selection is based on brain event-related responses measured with nine EEG sensors. Two players compete against each other using their brain activity only. Importantly, we turned the general difficulty of producing a reliable BCI command into an advantage, by extending the game play and rules, in a way that adds fun to the game and might well prove to trigger up motivation in future studies. The principle of this new BCI is directly inspired from our own implementation of the classical P300 Speller (Maby et al. 2010, Perrin et al. 2011). We here establish a proof of principle that the same electrophysiological markers can be used to design an efficient two-player game. Experimental evaluation on two competing healthy subjects yielded an average accuracy of 82%, which is in line with our previous results on many participants and demonstrates that the BCI “Connect Four” can effectively be controlled. Interestingly, the duration of the game is not significantly affected by the usual slowness of BCI commands. This suggests that this kind of BCI games could be of interest to healthy players as well as to disabled people who cannot play with classical games.

While functional imaging studies allow for a precise spatial characterization of resting state networks, their neural correlates and thereby their fine-scale temporal dynamics remain elusive. A full understanding of the mechanisms at play requires input from electrophysiological studies. Here, we discuss human and non-human primate electrophysiological data that explore the neural correlates of the default-mode network. Beyond the promising findings obtained with non-invasive approaches, emerging evidence suggests that invasive recordings in humans will be crucial in order to elucidate the neural correlates of the brain’s default-mode function. In particular, we contend that stereotactic-electroencephalography (SEEG), which consists of implanting multiple depth electrodes for pre-surgical evaluation in drug-resistant epilepsy, is particularly suited for this endeavor. We support this view by providing rare data from depth recordings in human posterior cingulate cortex and medial prefrontal cortex that show transient neural deactivation during task-engagement.

Congenital amusia is a neurogenetic disorder of music processing that is currently ascribed to a deficit in pitch processing. A recent study challenges this view and claims the disorder might arise as a consequence of a general spatial-processing deficit. Here, we assessed spatial processing abilities in two independent samples of individuals with congenital amusia by using line bisection tasks (Experiment 1) and a mental rotation task (Experiment 2). Both amusics and controls showed the classical spatial effects on bisection performance and on mental rotation performance, and amusics and controls did not differ from each other. These results indicate that the neurocognitive impairment of congenital amusia does not affect the processing of space.

BackgroundRh glycoproteins (RhAG, RhBG, RhCG) are members of the Amt/Mep/Rh family which facilitate movement of ammonium across plasma membranes. Changes in ammonium transport activity following expression of Rh glycoproteins have been described in different heterologous systems such as yeasts, oocytes and eukaryotic cell lines. However, in these complex systems, a potential contribution of endogenous proteins to this function cannot be excluded. To demonstrate that Rh glycoproteins by themselves transport NH(3), human RhCG was purified to homogeneity and reconstituted into liposomes, giving new insights into its channel functional properties.Methodology/principal findingsAn HA-tag introduced in the second extracellular loop of RhCG was used to purify to homogeneity the HA-tagged RhCG glycoprotein from detergent-solubilized recombinant HEK293E cells. Electron microscopy analysis of negatively stained purified RhCG-HA revealed, after image processing, homogeneous particles of 9 nm diameter with a trimeric protein structure. Reconstitution was performed with sphingomyelin, phosphatidylcholine and phosphatidic acid lipids in the presence of the C(12)E(8) detergent which was subsequently removed by Biobeads. Control of protein incorporation was carried out by freeze-fracture electron microscopy. Particle density in liposomes was a function of the Lipid/Protein ratio. When compared to empty liposomes, ammonium permeability was increased two and three fold in RhCG-proteoliposomes, depending on the Lipid/Protein ratio (1/300 and 1/150, respectively). This strong NH(3) transport was reversibly inhibited by mercuric and copper salts and exhibited a low Arrhenius activation energy.Conclusions/significanceThis study allowed the determination of ammonia permeability per RhCG monomer, showing that the apparent Punit(NH3) (around 1x10(-3) microm(3)xs(-1)) is close to the permeability measured in HEK293E cells expressing a recombinant human RhCG (1.60x10(-3) microm(3)xs(-1)), and in human red blood cells endogenously expressing RhAG (2.18x10(-3) microm(3)xs(-1)). The major finding of this study is that RhCG protein is active as an NH(3) channel and that this function does not require any protein partner.

For patients with pharmaco-resistant temporal epilepsy, unilateral anterior temporal lobectomy (ATL) - i.e. the surgical resection of the hippocampus, the amygdala, the temporal pole and the most anterior part of the temporal gyri - is an efficient treatment. There is growing evidence that anterior regions of the temporal lobe are involved in the integration and short-term memorization of object-related sound properties. However, non-verbal auditory processing in patients with temporal lobe epilepsy (TLE) has raised little attention. To assess non-verbal auditory cognition in patients with temporal epilepsy both before and after unilateral ATL, we developed a set of non-verbal auditory tests, including environmental sounds. We could evaluate auditory semantic identification, acoustic and object-related short-term memory, and sound extraction from a sound mixture. The performances of 26 TLE patients before and/or after ATL were compared to those of 18 healthy subjects. Patients before and after ATL were found to present with similar deficits in pitch retention, and in identification and short-term memorisation of environmental sounds, whereas not being impaired in basic acoustic processing compared to healthy subjects. It is most likely that the deficits observed before and after ATL are related to epileptic neuropathological processes. Therefore, in patients with drug-resistant TLE, ATL seems to significantly improve seizure control without producing additional auditory deficits.

In our complex acoustic environment, we are confronted with a mixture of sounds produced by several simultaneous sources. However, we rarely perceive these sounds as incomprehensible noise. Our brain uses perceptual organization processes to independently follow the emission of each sound source over time. If the acoustic properties exploited in these processes are well-established, the neurophysiological mechanisms involved in auditory scene analysis have raised interest only recently. Here, we review the studies investigating these mechanisms using electrophysiological recordings from the cochlear nucleus to the auditory cortex, in animals and humans. Their findings reveal that basic mechanisms such as frequency selectivity, forward suppression and multi-second habituation shape the automatic brain responses to sounds in a way that can account for several important characteristics of perceptual organization of both simultaneous and successive sounds. One challenging question remains unresolved: how are the resulting activity patterns integrated to yield the corresponding conscious perceptsµ

BackgroundTinnitus is an auditory phantom perception that is most likely generated in the central nervous system. Most of the tinnitus research has concentrated on the auditory system. However, it was suggested recently that also non-auditory structures are involved in a global network that encodes subjective tinnitus. We tested this assumption using auditory steady state responses to entrain the tinnitus network and investigated long-range functional connectivity across various non-auditory brain regions.Methods and findingsUsing whole-head magnetoencephalography we investigated cortical connectivity by means of phase synchronization in tinnitus subjects and healthy controls. We found evidence for a deviating pattern of long-range functional connectivity in tinnitus that was strongly correlated with individual ratings of the tinnitus percept. Phase couplings between the anterior cingulum and the right frontal lobe and phase couplings between the anterior cingulum and the right parietal lobe showed significant condition x group interactions and were correlated with the individual tinnitus distress ratings only in the tinnitus condition and not in the control conditions.ConclusionsTo the best of our knowledge this is the first study that demonstrates existence of a global tinnitus network of long-range cortical connections outside the central auditory system. This result extends the current knowledge of how tinnitus is generated in the brain. We propose that this global extend of the tinnitus network is crucial for the continuos perception of the tinnitus tone and a therapeutical intervention that is able to change this network should result in relief of tinnitus.

BACKGROUND: The surgical treatment of patients with intractable epilepsy is preceded by a pre-surgical evaluation period during which intracranial EEG recordings are performed to identify the epileptogenic network and provide a functional map of eloquent cerebral areas that need to be spared to minimize the risk of post-operative deficits. A growing body of research based on such invasive recordings indicates that cortical oscillations at various frequencies, especially in the gamma range (40 to 150 Hz), can provide efficient markers of task-related neural network activity. PRINCIPAL FINDINGS: Here we introduce a novel real-time investigation framework for mapping human brain functions based on online visualization of the spectral power of the ongoing intracranial activity. The results obtained with the first two implanted epilepsy patients who used the proposed online system illustrate its feasibility and utility both for clinical applications, as a complementary tool to electrical stimulation for presurgical mapping purposes, and for basic research, as an exploratory tool used to detect correlations between behavior and oscillatory power modulations. Furthermore, our findings suggest a putative role for high gamma oscillations in higher-order auditory processing involved in speech and music perception. CONCLUSION/SIGNIFICANCE: The proposed real-time setup is a promising tool for presurgical mapping, the investigation of functional brain dynamics, and possibly for neurofeedback training and brain computer interfaces.