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Khoomei is a unique singing style originating from the Central Asian republic of Tuva. Singers produce two pitches simultaneously: a booming low-frequency rumble alongside a hovering high-pitched whistle-like tone. The biomechanics of this biphonation are not well-understood. Here, we use sound analysis, dynamic magnetic resonance imaging, and vocal tract modeling to demonstrate how biphonation is achieved by modulating vocal tract morphology. Tuvan singers show remarkable control in shaping their vocal tract to narrowly focus the harmonics (or overtones) emanating from their vocal cords. The biphonic sound is a combination of the fundamental pitch and a focused filter state, which is at the higher pitch (1-2 kHz) and formed by merging two formants, thereby greatly enhancing sound-production in a very narrow frequency range. Most importantly, we demonstrate that this biphonation is a phenomenon arising from linear filtering rather than a nonlinear source. Data is placed in four zipped files (compression done via Mac OS 10.12.4). The four files each contain a particular subset of the data: 1. Model.zip - Modeling software (Tube Talker) and several illustrative simulations 2. CroppedMRI_CB.zip - Both statis and dynamic MRI images (as .dcm files). Note that the DICOM files have been cropped (so to only show the relevant anatomical features) and metadata have been stripped. 3. SoundboothRecordings.zip - All soundbooth recordings, saved as .wav files (SR 96 kHz) 4. STL.zip - Reonstruction of the 3-D airspace, saved as a .stl file 5. MRIaudio.zip - Audio files collected during the MRI runs 6. MRImoviesC.zip - Movies of the dynamic data (with audio). Data is a combination of acoustical recordings, MRI data, and vocal tract modeling. Movie of the dynamic MRI data are also included. All details are included in the manuscript "Overtone focusing in biphonic Tuvan throat singing".

We introduce Sleep, a new Python open-source graphical user interface (GUI) dedicated to visualization, scoring and analyses of sleep data. Among its most prominent features are: (1) Dynamic display of polysomnographic data, spectrogram, hypnogram and topographic maps with several customizable parameters, (2) Implementation of several automatic detection of sleep features such as spindles, K-complexes, slow waves, and rapid eye movements (REM), (3) Implementation of practical signal processing tools such as re-referencing or filtering, and (4) Display of main descriptive statistics including publication-ready tables and figures. The software package supports loading and reading raw EEG data from standard file formats such as European Data Format, in addition to a range of commercial data formats. Most importantly, Sleep is built on top of the VisPy library, which provides GPU-based fast and high-level visualization. As a result, it is capable of efficiently handling and displaying large sleep datasets. Sleep is freely available (http://visbrain.org/sleep) and comes with sample datasets and an extensive documentation. Novel functionalities will continue to be added and open-science community efforts are expected to enhance the capacities of this module.

Although it is well known that long-term synaptic plasticity can be expressed both pre- and postsynaptically, the functional consequences of this arrangement have remained elusive. We show that spike-timing-dependent plasticity with both pre- and postsynaptic expression develops receptive fields with reduced variability and improved discriminability compared to postsynaptic plasticity alone. These long-term modifications in receptive field statistics match recent sensory perception experiments. Moreover, learning with this form of plasticity leaves a hidden postsynaptic memory trace that enables fast relearning of previously stored information, providing a cellular substrate for memory savings. Our results reveal essential roles for presynaptic plasticity that are missed when only postsynaptic expression of long-term plasticity is considered, and suggest an experience-dependent distribution of pre- and postsynaptic strength changes. STDP dataset with estimated changes in P , q and the mean weightprepostSTDP.xls

Appropriate response to others is necessary for social interactions. Yet little is known about how neurotransmitters regulate attractive and repulsive social cues. Using genetic and pharmacological manipulations in Drosophila melanogaster, we show that dopamine is contributing the response to others in a social group, specifically, social spacing, but not the avoidance of odours released by stressed flies (dSO). Interestingly, this dopamine-mediated behaviour is prominent only in the day-time, and its effect varies depending on tissue, sex and type of manipulation. Furthermore, alteration of dopamine levels has no effect on dSO avoidance regardless of sex, which suggests that a different neurotransmitter regulates this response. DA_Social_PaperRaw social space data in cm, dSO performance index and locomotion (numbers of lines crossed in 1 min. All details of how the data were obtained can be found in the material and methods of the paper.

A prevalent model is that sharp-wave ripples (SWR) arise ‘spontaneously’ in CA3 and propagate recent memory traces outward to the neocortex to facilitate memory consolidation there. Using voltage and extracellular glutamate transient recording over widespread regions of mice dorsal neocortex in relation to CA1 multiunit activity (MUA) and SWR, we find that the largest SWR-related modulation occurs in retrosplenial cortex; however, contrary to the unidirectional hypothesis, neocortical activation exhibited a continuum of activation timings relative to SWRs, varying from leading to lagging. Thus, contrary to the model in which SWRs arise ‘spontaneously’ in the hippocampus, neocortical activation often precedes SWRs and may thus constitute a trigger event in which neocortical information seeds associative reactivation of hippocampal ‘indices’. This timing continuum is consistent with a dynamics in which older, more consolidated memories may in fact initiate the hippocampal-neocortical dialog, whereas reactivation of newer memories may be initiated predominantly in the hippocampus.

Kwan et al.,Dryad_data_FinalDue to anthropogenic CO2 emissions and the subsequent process of ocean acidification (OA), open ocean surface CO2 levels are projected to more than double to ~1,000 μatm, and pH to decrease by ~0.3 units by the year 2100. When exposed to these CO2/pH values, several fish species display abnormal behaviour in laboratory tests, an effect proposed to be linked to altered neuronal GABAA receptor function. This study examined the effects of constant and oscillating OA-like conditions on individual and group behaviour of juvenile blacksmith (Chromis punctipinnis), a social fish that regularly experiences CO2/pH fluctuations through kelp forest diurnal primary production and upwelling events. Blacksmiths were exposed to three treatments: control (pH ~7.92; pCO2 ~540 μatm); constant acidification (pH ~7.72; pCO2 ~920 μatm); and oscillating acidification (pH ~7.92, pCO2 ~560 μatm (day), pH ~7.75, pCO2 ~955 μatm (night)). After seven and eleven days, respectively, blacksmiths were administered individual light/dark preference and group shoaling tests, which are well-validated measures of anxiety-like behaviour and are modulated by GABAA receptors. In addition, to investigate potential interactions between OA and season of the year, the effect of CO2/pH on individual blacksmith behaviour was tested in January (16.50 ± 0.01oC) and September (23.10 ± 0.01 oC). While season had a significant effect on light/dark preference, oscillating acidification did not affect any behavioural parameter, suggesting blacksmiths are tolerant to projected future OA conditions. Open ocean surface CO2 levels are projected to reach approximately 800 µatm, and ocean pH to decrease by approximately 0.3 units by the year 2100 due to anthropogenic CO2 emissions and the subsequent process of ocean acidification (OA). When exposed to these CO2/pH values, several fish species display abnormal behaviour in laboratory tests, an effect proposed to be linked to altered neuronal GABAA­ receptor function. Juvenile blacksmith (Chromis punctipinnis) are social fish that regularly experience CO2/pH fluctuations through kelp forest diurnal primary production and upwelling events, so we hypothesized that they might be resilient to OA. Blacksmiths were exposed to control conditions (pH ∼ 7.92; pCO2 ∼ 540 µatm), constant acidification (pH ∼ 7.71; pCO2 ∼ 921 µatm) and oscillating acidification (pH ∼ 7.91, pCO2 ∼ 560 µatm (day), pH ∼ 7.70, pCO2 ∼ 955 µatm (night)), and caught and tested in two seasons of the year when the ocean temperature was different: winter (16.5 ± 0.1°C) and summer (23.1 ± 0.1°C). Neither constant nor oscillating CO2-induced acidification affected blacksmith individual light/dark preference, inter-individual distance in a shoal or the shoal's response to a novel object, suggesting that blacksmiths are tolerant to projected future OA conditions. However, blacksmiths tested during the winter demonstrated significantly higher dark preference in the individual light/dark preference test, thus confirming season and/or water temperature as relevant factors to consider in behavioural tests.

Belyk_RSOS_opendata_c1Raw fMRI and skull-stripped structural MRI data for participant c1c1.zipBelyk_RSOS_opendata_c2Raw fMRI and skull-stripped structural MRI data for participant c2c2.zipBelyk_RSOS_opendata_c3Raw fMRI and structural MRI data for participant c3c3b.zipBelyk_RSOS_opendata_c4Raw fMRI and skull-stripped structural MRI data for participant c4c4.zipBelyk_RSOS_opendata_c5Raw fMRI and skull-stripped structural MRI data for participant c5c5.zipBelyk_RSOS_opendata_c6Raw fMRI and structural MRI data for participant c6c6.zipBelyk_RSOS_opendata_c10Raw fMRI and skull-stripped MRI data for participant c10c10.zipBelyk_RSOS_opendata_c11Raw fMRI and skull-stripped MRI data for participant c11c11.zipBelyk_RSOS_opendata_c12Raw fMRI and skull-stripped structural MRI data for participant c12c12.zipBelyk_RSOS_opendata_c13Raw fMRI and skull-stripped structural MRI data for participant c13c13.zipBelyk_RSOS_opendata_c14Raw fMRI and skull-stripped structural MRI data for participant c14c14.zipBelyk_RSOS_opendata_c15Raw fMRI and skull-stripped structural MRI data for participant c15c15.zipBelyk_RSOS_opendata_designExperimental design and timing information. Each subfolder contains the start times of experimental blocks for low, comfort, middle, and high pitch blocks, measured in acquisition volumes.design.zip Vocal pitch is used as an important communicative device by humans, as found in the melodic dimension of both speech and song. Vocal pitch is determined by the degree of tension in the vocal folds of the larynx, which itself is influenced by complex and non-linear interactions among the laryngeal muscles. The relationship between these muscles and vocal pitch has been described by a mathematical model in the form of a set of “control rules”. We searched for the biological implementation of these control rules in the larynx motor cortex (LMC) of the human brain. We scanned choral singers with functional magnetic resonance imaging as they produced discrete pitches at four different levels across their vocal range. While the locations of the larynx motor activations varied across singers, the activation peaks for the four pitch-levels were highly consistent within each individual singer. This result was corroborated using multivoxel pattern analysis, which demonstrated an absence of patterned activations differentiating any pairing of pitch-levels. The complex and non-linear relationships between the multiple laryngeal muscles that control vocal pitch may obscure the neural encoding of vocal pitch in the brain.

Contraction-level invariant surface electromyography pattern recognition introduces the decrease of training time and decreases the limitation of clinical prostheses. This study intended to examine whether a signal pre-processing method named frequency division technique (FDT) for online myoelectric pattern recognition classification is robust against contraction-level variation, and whether this pre-processing method has an advantage over traditional time-domain pattern recognition techniques even in the absence of muscle contraction-level variation. Eight healthy and naïve subjects performed wrist contractions during two degrees of freedom goal-oriented tasks, divided in three groups of type I, type II, and type III. The performance of these tasks, when the two different methods were used, was quantified by completion rate, completion time, throughput, efficiency, and overshoot. The traditional and the FDT method were compared in four runs, using combinations of normal or high muscle contraction level, and the traditional method or FDT. The results indicated that FDT had an advantage over traditional methods in the tested real-time myoelectric control tasks. FDT had a much better median completion rate of tasks (95%) compared to the traditional method (77.5%) among non-perfect runs, and the variability in FDT was strikingly smaller than the traditional method (p < 0.001). Moreover, the FDT method outperformed the traditional method in case of contraction-level variation between the training and online control phases (p = 0. 005 for throughput in type I tasks with normal contraction level, p = 0.006 for throughput in type II tasks, and p = 0.001 for efficiency with normal contraction level of all task types). This study shows that FDT provides advantages in online myoelectric control as it introduces robustness over contraction-level variations.

Objective: To investigate the efficacy and safety of aceneuramic acid extended-release (Ace-ER), a treatment intended to replace deficient sialic acid, in patients with GNE myopathy. Methods: UX001-CL301 was a Phase 3, double-blind, placebo-controlled, randomized, international study evaluating the efficacy and safety of Ace-ER in patients with GNE Myopathy. Participants who could walk ≥200 meters in a 6-minute walk test at screening were randomized 1:1, and stratified by sex, to receive Ace-ER 6g/day or placebo for 48 weeks and assessed every 8 weeks. The primary endpoint was change in muscle strength over 48 weeks measured by Upper Extremity Composite (UEC) score. Key secondary endpoints included change in Lower Extremity Composite (LEC) score, knee extensor strength, and GNE myopathy-Functional Activity Scale (GNEM-FAS) mobility domain score. Safety assessments included adverse events (AEs), vital signs, and clinical laboratory results. Results: Eighty-nine patients were randomized (Ace-ER n = 45; Placebo n = 44). Change from baseline to week 48 for UEC score between treatments did not differ (least square mean [LSM] Ace-ER -2.25 kg vs Placebo -2.99 kg; LSM difference (confidence interval [CI]) 0.74 (-1.61, 3.09); p = 0.5387). At week 48, there was no significant difference between treatments for the change in key secondary endpoints: LEC LSM difference (CI) -1.49 (-5.83, 2.86); knee extension strength -0.40 (-2.38, 1.58); and GNEM-FAS mobility domain score -0.72 (-2.01, 0.57). Gastrointestinal events were the most common AEs. Conclusions: Ace-ER was not superior to placebo in improving muscle strength and function in patients with GNE myopathy. Lochmuller et al UX001 CL301 MS supp materials protocol 13Dec2018Supplemental Material for Lochmuller et al Neurology: Table e-1. Change from Baseline to Week 48 in UEC and LEC Individual Muscle Groups with Hand-Held Dynamometry; Figure e-1. UX001-CL301 CONSORT Flow Diagram; UX001-CL301 Protocol