Estimating the Intended Sound Direction of the User: Toward an Auditory Brain-Computer Interface Using Out-of-Head Sound Localization

The auditory Brain-Computer Interface (BCI) using electroencephalograms (EEG) is a subject of intensive study. As a cue, auditory BCIs can deal with many of the characteristics of stimuli such as tone, pitch, and voices. Spatial information on auditory stimuli also provides useful information for a BCI. However, in a portable system, virtual auditory stimuli have to be presented spatially through earphones or headphones, instead of loudspeakers. We investigated the possibility of an auditory BCI using the out-of-head sound localization technique, which enables us to present virtual auditory stimuli to users from any direction, through earphones. The feasibility of a BCI using this technique was evaluated in an EEG oddball experiment and offline analysis. A virtual auditory stimulus was presented to the subject from one of six directions. Using a support vector machine, we were able to classify whether the subject attended the direction of a presented stimulus from EEG signals. The mean accuracy across subjects was 70.0% in the single-trial classification. When we used trial-averaged EEG signals as inputs to the classifier, the mean accuracy across seven subjects reached 89.5% (for 10-trial averaging). Further analysis showed that the P300 event-related potential responses from 200 to 500 ms in central and posterior regions of the brain contributed to the classification. In comparison with the results obtained from a loudspeaker experiment, we confirmed that stimulus presentation by out-of-head sound localization achieved similar event-related potential responses and classification performances. These results suggest that out-of-head sound localization enables us to provide a high-performance and loudspeaker-less portable BCI system.     

Brain-Computer Interface Speller System for Alternative Communication: A Review

Brain-computer interface (BCI) speller is a system that provides an alternative communication for the disable people. The brain wave is translated into machine command through a BCI speller which can be used as a communication medium for the patients to express their thought without any motor movement. A BCI speller aims to spell characters by using the electroencephalogram (EEG) signal. Several types of BCI spellers are available based on the EEG signal. A standard BCI speller system consists of the following elements: BCI speller paradigm, data acquisition system and signal processing algorithms. In this work, a systematic review is provided on the BCI speller system and it includes speller paradigms, feature extraction, feature optimization and classification techniques for BCI speller. The advantages and limitations of different speller paradigm and machine learning algorithms are discussed in this article. Also, the future research directions are discussed which can overcome the limitations of present state-of-the-art techniques for BCI speller.     

A Psychophysical Imaging Method Evidencing Auditory Cue Extraction during Speech Perception: A Group Analysis of Auditory Classification Images

Although there is a large consensus regarding the involvement of specific acoustic cues in speech perception, the precise mechanisms underlying the transformation from continuous acoustical properties into discrete perceptual units remains undetermined. This gap in knowledge is partially due to the lack of a turnkey solution for isolating critical speech cues from natural stimuli. In this paper, we describe a psychoacoustic imaging method known as the Auditory Classification Image technique that allows experimenters to estimate the relative importance of time-frequency regions in categorizing natural speech utterances in noise. Importantly, this technique enables the testing of hypotheses on the listening strategies of participants at the group level. We exemplify this approach by identifying the acoustic cues involved in da/ga categorization with two phonetic contexts, Al- or Ar-. The application of Auditory Classification Images to our group of 16 participants revealed significant critical regions on the second and third formant onsets, as predicted by the literature, as well as an unexpected temporal cue on the first formant. Finally, through a cluster-based nonparametric test, we demonstrate that this method is sufficiently sensitive to detect fine modifications of the classification strategies between different utterances of the same phoneme.     

Tetrapod Ichnofacies: A New Paradigm

We recognize three fundamental terms in ichnology: (1) ichnoassemblage, which is an assemblage of ichnofossils conceptually equivalent to an assemblage of body fossils; (2) ichnocoenosis, which is a trace fossil assemblage produced by a biological community that can be characterized by morphological criteria; and (3) ichnofacies, which refers to recurrent ichnocoenoses that represent a significant portion of Phanerozoic time. There are two different kinds of ichnofacies, ethoichnofacies (mostly invertebrate ichnofacies) and biotaxonichnofacies (mostly tetrapod ichnofacies). Nonmarine invertebrate ichnologists now recognize five archetypal ichnofacies (Mermia, Skolithos, Scoyenia, Coprinisphaera, Psilonichnus) to which we add the Octopodichnus ichnofacies. We propose a coherent and consistent classification and nomenclature for tetrapod ichnofacies. We name five archetypal vertebrate ichnofacies for nonmarine environments: Chelichnus, Grallator, Brontopodus, Batrachichnus and Characichnos ichnofacies.     

Emerging and Reemerging Infectious Diseases: Biocomplexity as an Interdisciplinary Paradigm

Understanding factors responsible for reemergence of diseases believed to have been controlled and outbreaks of previously unknown infectious diseases is one of the most difficult scientific problems facing society today. Significant knowledge gaps exist for even the most studied emerging infectious diseases. Coupled with failures in the response to the resurgence of infectious diseases, this lack of information is embedded in a simplistic view of pathogens and disconnected from a social and ecological context, and assumes a linear response of pathogens to environmental change. In fact, the natural reservoirs and transmission rates of most emerging infectious diseases primarily are affected by environmental factors, such as seasonality or meteorological events, typically producing nonlinear responses that are inherently unpredictable. A more realistic view of emerging infectious diseases requires a holistic perspective that incorporates social as well as physical, chemical, and biological dimensions of our planet’s systems. The notion of biocomplexity captures this depth and richness, and most importantly, the interactions of human and natural systems. This article provides a brief review and a synthesis of interdisciplinary approaches and insights employing the biocomplexity paradigm and offers a social–ecological approach for addressing and garnering an improved understanding of emerging infectious diseases. Drawing on findings from studies of cholera and other examples of emerging waterborne, zoonotic, and vectorborne diseases, a “blueprint” for the proposed interdisciplinary research framework is offered which integrates biological processes from the molecular level to that of communities and regional systems, incorporating public health infrastructure and climate aspects.     

A Brain-Computer Interface Based Cognitive Training System for Healthy Elderly: A Randomized Control Pilot Study for Usability and Preliminary Efficacy

Cognitive decline in aging is a pressing issue associated with significant healthcare costs and deterioration in quality of life. Previously, we reported the successful use of a novel brain-computer interface (BCI) training system in improving symptoms of attention deficit hyperactivity disorder. Here, we examine the feasibility of the BCI system with a new game that incorporates memory training in improving memory and attention in a pilot sample of healthy elderly. This study investigates the safety, usability and acceptability of our BCI system to elderly, and obtains an efficacy estimate to warrant a phase III trial. Thirty-one healthy elderly were randomized into intervention (n = 15) and waitlist control arms (n = 16). Intervention consisted of an 8-week training comprising 24 half-hour sessions. A usability and acceptability questionnaire was administered at the end of training. Safety was investigated by querying users about adverse events after every session. Efficacy of the system was measured by the change of total score from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) before and after training. Feedback on the usability and acceptability questionnaire was positive. No adverse events were reported for all participants across all sessions. Though the median difference in the RBANS change scores between arms was not statistically significant, an effect size of 0.6SD was obtained, which reflects potential clinical utility according to Simon’s randomized phase II trial design. Pooled data from both arms also showed that the median change in total scores pre and post-training was statistically significant (Mdn = 4.0; p<0.001). Specifically, there were significant improvements in immediate memory (p = 0.038), visuospatial/constructional (p = 0.014), attention (p = 0.039), and delayed memory (p<0.001) scores. Our BCI-based system shows promise in improving memory and attention in healthy elderly, and appears to be safe, user-friendly and acceptable to senior users. Given the efficacy signal, a phase III trial is warranted.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01661894","term_id":"NCT01661894"}}NCT01661894     

Epigenome-Wide DNA Methylation in Hearing Ability: New Mechanisms for an Old Problem

Epigenetic regulation of gene expression has been shown to change over time and may be associated with environmental exposures in common complex traits. Age-related hearing impairment is a complex disorder, known to be heritable, with heritability estimates of 57–70%. Epigenetic regulation might explain the observed difference in age of onset and magnitude of hearing impairment with age. Epigenetic epidemiology studies using unrelated samples can be limited in their ability to detect small effects, and recent epigenetic findings in twins underscore the power of this well matched study design. We investigated the association between venous blood DNA methylation epigenome-wide and hearing ability. Pure-tone audiometry (PTA) and Illumina HumanMethylation array data were obtained from female twin volunteers enrolled in the TwinsUK register. Two study groups were explored: first, an epigenome-wide association scan (EWAS) was performed in a discovery sample (n = 115 subjects, age range: 47–83 years, Illumina 27 k array), then replication of the top ten associated probes from the discovery EWAS was attempted in a second unrelated sample (n = 203, age range: 41–86 years, Illumina 450 k array). Finally, a set of monozygotic (MZ) twin pairs (n = 21 pairs) within the discovery sample (Illumina 27 k array) was investigated in more detail in an MZ discordance analysis. Hearing ability was strongly associated with DNA methylation levels in the promoter regions of several genes, including TCF25 (cg01161216, p = 6.6×10⁻⁶), FGFR1 (cg15791248, p = 5.7×10⁻⁵) and POLE (cg18877514, p = 6.3×10⁻⁵). Replication of these results in a second sample confirmed the presence of differential methylation at TCF25 (p(replication) = 6×10⁻⁵) and POLE (p(replication) = 0.016). In the MZ discordance analysis, twins'' intrapair difference in hearing ability correlated with DNA methylation differences at ACP6 (cg01377755, r = −0.75, p = 1.2×10⁻⁴) and MEF2D (cg08156349, r = −0.75, p = 1.4×10⁻⁴). Examination of gene expression in skin, suggests an influence of differential methylation on expression, which may account for the variation in hearing ability with age.     

A New Paradigm for Developmental Science: Relationism and Relational-Developmental Systems

The Cartesian-Split-Mechanistic scientific paradigm that until recently functioned as the standard conceptual framework for sub-fields of developmental science (including inheritance, evolution, and organismic—pre-natal, cognitive, emotional, motivational, socio-cultural—development) has been progressively failing as a scientific research program. An alternative scientific paradigm composed of nested meta-theories with Relationism at the broadest level and Relational-Developmental-Systems as a mid-range meta-theory is offered as a more progressive conceptual framework for developmental science. Termed broadly the Relational-Developmental-Systems paradigm, this framework accounts for the findings that are anomalies for the old paradigm, accounts for the emergence of new findings, and points the way to future scientific productivity—and a more optimistic approach to evaluate-evidence-based applications aimed at promoting positive human development and social justice.     

Restoration Ecology to the Future: A Call for New Paradigm

The discipline of restoration ecology has grown remarkably in the past decades, providing new ideas and opportunities for conserving biological diversity, managing ecosystems, and testing ecological theories. On the other side, its past‐oriented, static, and idealistic approach has been criticized for subjectivity in determining restoration goals, inapplicability to dynamic ecosystems, and inability for restoring certain irreversible losses. Moreover, unpredictable sustainability of the restored ecosystems, which were modeled after its historical fidelity, adds our skepticism under the changing environment. This paper calls for a new paradigm of ecological restoration to the future. A future‐oriented restoration should (1) establish the ecosystems that are able to sustain in the future, not the past, environment; (2) have multiple alternative goals and trajectories for unpredictable endpoints; (3) focus on rehabilitation of ecosystem functions rather than recomposition of species or cosmetics of landscape surface; and (4) acknowledge its identity as a “value‐laden” applied science within economically and socially acceptable framework. Applicability of ecological theories to restoration practice is also discussed in this paper.     

A P300-based Brain-Computer Interface with Stimuli on Moving Objects: Four-Session Single-Trial and Triple-Trial Tests with a Game-Like Task Design

Brain-computer interfaces (BCIs) are tools for controlling computers and other devices without using muscular activity, employing user-controlled variations in signals recorded from the user’s brain. One of the most efficient noninvasive BCIs is based on the P300 wave of the brain’s response to stimuli and is therefore referred to as the P300 BCI. Many modifications of this BCI have been proposed to further improve the BCI’s characteristics or to better adapt the BCI to various applications. However, in the original P300 BCI and in all of its modifications, the spatial positions of stimuli were fixed relative to each other, which can impose constraints on designing applications controlled by this BCI. We designed and tested a P300 BCI with stimuli presented on objects that were freely moving on a screen at a speed of 5.4°/s. Healthy participants practiced a game-like task with this BCI in either single-trial or triple-trial mode within four sessions. At each step, the participants were required to select one of nine moving objects. The mean online accuracy of BCI-based selection was 81% in the triple-trial mode and 65% in the single-trial mode. A relatively high P300 amplitude was observed in response to targets in most participants. Self-rated interest in the task was high and stable over the four sessions (the medians in the 1st/4th sessions were 79/84% and 76/71% in the groups practicing in the single-trial and triple-trial modes, respectively). We conclude that the movement of stimulus positions relative to each other may not prevent the efficient use of the P300 BCI by people controlling their gaze, e.g., in robotic devices and in video games.     

Use of a Vacuum-Assisted Device for Fournier's Gangrene: A New Paradigm

Fournier's gangrene is a necrotizing infection of the scrotum or perineum that requires aggressive surgical debridement. Radical debridement of perineal necrotizing fasciitis can leave extensive tissue defects that are difficult to close and often require multiple surgical interventions. Vacuum-assisted closure (VAC) devices have been shown to assist in a more rapid closure of these wounds, but placement of such devices in the perineum can pose significant challenges. We have had success with use of VAC devices and report our techniques for their placement.     

Focal Therapy: A New Paradigm for the Treatment of Prostate Cancer

Focal therapy has been proposed in recent years as a means of bridging the gap between radical prostatectomy and active surveillance for treatment of prostate cancer. The rationale for focal therapy comes from its success in treating other malignancies. One of the challenges in applying such an approach to the treatment of prostate cancer has been the multifocal nature of the disease. This review addresses the selection of potentially ideal candidates for focal therapy and discusses which modalities are currently being used and proposed for focal therapy. Setting and meeting guidelines for oncologic efficacy is a challenge we must embrace to safely deliver this potentially revolutionary approach to treating men with prostate cancer.Key words: Focal therapy, Photodynamic therapy, Prostatic neoplasms, Prostate-specific antigen, Prostatectomy, Ultrasound, high-intensity focused, transrectal, CryosurgeryWith the advent of prostate-specific antigen (PSA) screening there has been a stage migration, with radical prostatectomy (RP) being performed with increasing frequency in men with low-risk disease.¹ Whole gland treatment of prostate cancer carries a significant risk of incontinence and sexual dysfunction. Even in the most experienced centers, the rate of potency following RP is approximately 60%.^2–4 Stage migration has led many to recommend active surveillance (AS) as a means to decrease the number of men who may be overtreated; however, AS has been slow to gain acceptance in the United States.An analysis of over 5300 men from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) National Prostate Cancer Registry⁵ showed that only 7% of men with clinically localized prostate cancer chose AS as an initial option. Aside from the anxiety that stems from not treating a diagnosed cancer, the greater difficulty with AS lies in selection of candidates and appropriate parameters for surveillance, allowing prompt intervention without compromising cure rates.Focal therapy has been proposed in recent years as a means of bridging the gap between whole gland treatment and AS. Many believe that for patients with low-risk disease, focal therapy is the ideal option for maximizing quality of life by avoiding the effects of whole gland radiation or surgery while alleviating the anxiety and uncertainty of AS. The definition of focal therapy itself is not well established and includes lesion-targeted therapy (LAT), hemiablative therapy (HAT), or subtotal gland therapy (STAT), sparing at least 1 neurovascular bundle.⁶The rationale for focal therapy comes from its success in treating other malignancies. In breast cancer treatment, for example, radical mastectomy has been replaced in many instances by local excision and Mohs surgery has led to less radical surgery for the treatment of melanoma.⁷ In our own field, the push for nephron-sparing surgery has led to the favoring of partial nephrectomy in tumors less than 7 cm, with oncologic outcomes similar to those of radical nephrectomy.⁸The challenge in applying such an approach to the treatment of prostate cancer has been the multifocal nature of prostate cancer and the fact that most cancers are detected without identifying a lesion on palpation or imaging studies.^9,10In this review, we revisit the current status of focal therapy in the treatment of prostate cancer. We discuss whether there are ideal candidates for focal therapy; we then discuss how these candidates should be selected. We review which modalities are currently being used and proposed for focal therapy. Finally, we discuss potential definitions of successful treatment. As this article shows, there are still many aspects of focal therapy that are yet to be defined, that warrant a great need for further research.     

Intravenous Therapy Duration and Outcomes in Melioidosis: A New Treatment Paradigm

BackgroundInternational melioidosis treatment guidelines recommend a minimum 10 to 14 days’ intravenous antibiotic therapy (intensive phase), followed by 3 to 6 months’ oral therapy (eradication phase). This approach is associated with rates of relapse, defined as recurrence following the eradication phase, that can exceed 5%. Rates of recrudescence, defined as recurrence during the eradication phase, have not previously been reported. In response to low eradication phase completion rates in Australia, a local guideline has evolved over the last ten years recommending a longer minimum intensive phase duration for many cases of melioidosis.

Methodology/ Principal Findings

This retrospective cohort study reviews antibiotic duration for the first episode of care for all patients diagnosed with melioidosis and surviving the intensive phase during a recent three year period in the tropical north of Australia’s Northern Territory; we also review adherence to the current local guideline and treatment outcomes. Of 215 first episodes of melioidosis surviving the intensive phase, the median (interquartile range) intensive phase duration was 26 (14-34) days. One hundred and eight (50.2%) patients completed eradication therapy; 58 (27.0%) patients took no eradication therapy. At 28 months’ follow-up, one (0.5%) relapse and eleven (5.1%) recrudescences had occurred. On exact logistic regression analysis, the only independent risk factors for recrudescence were self-discharge during the intensive phase (odds ratio 6.2 [95% confidence interval 1.2-30.0]) and septic shock (odds ratio 5.3 [95% confidence interval 1.1-25.7]).

Conclusions/ Significance

Relapsed melioidosis is rare in patients who receive a minimum intensive phase duration specified by our guideline and extended according to clinical progress. Recrudescence rates may improve with reductions in rates of self-discharge. Given the low relapse rate despite a high rate of eradication therapy non-adherence, the duration and necessity of eradication therapy for different patients after guideline-concordant intensive therapy should be evaluated further.     

Different Stimuli,Different Spatial Codes: A Visual Map and an Auditory Rate Code for Oculomotor Space in the Primate Superior Colliculus

Maps are a mainstay of visual, somatosensory, and motor coding in many species. However, auditory maps of space have not been reported in the primate brain. Instead, recent studies have suggested that sound location may be encoded via broadly responsive neurons whose firing rates vary roughly proportionately with sound azimuth. Within frontal space, maps and such rate codes involve different response patterns at the level of individual neurons. Maps consist of neurons exhibiting circumscribed receptive fields, whereas rate codes involve open-ended response patterns that peak in the periphery. This coding format discrepancy therefore poses a potential problem for brain regions responsible for representing both visual and auditory information. Here, we investigated the coding of auditory space in the primate superior colliculus(SC), a structure known to contain visual and oculomotor maps for guiding saccades. We report that, for visual stimuli, neurons showed circumscribed receptive fields consistent with a map, but for auditory stimuli, they had open-ended response patterns consistent with a rate or level-of-activity code for location. The discrepant response patterns were not segregated into different neural populations but occurred in the same neurons. We show that a read-out algorithm in which the site and level of SC activity both contribute to the computation of stimulus location is successful at evaluating the discrepant visual and auditory codes, and can account for subtle but systematic differences in the accuracy of auditory compared to visual saccades. This suggests that a given population of neurons can use different codes to support appropriate multimodal behavior.     

空间分子生态学——分子生态学与空间生态学相结合的新领域

分子标记、基因流、种群空间动态是当前生命科学研究中的热点领域。RFLPs、RAPDs、微卫星等新的分子标记的不断涌现,促进了这些领域的飞速发展。对种群空间动态研究中的等级岛屿模型、距离隔离模型、脚踏石模型、集合种群模型等方面许多令人瞩目的进展做了介绍。同时还介绍了遗传距离、基因流及其测度、基因突变模型、3S技术、空间精确性种群模型和基因频率的空间自相关等热点领域。最后,就空间分子生态学存在的问题与前景进行了讨论,指出了空间分子生态学可能的发展方向。