Connectome-driven neural inventory of a complete visual system.

Vision provides animals with detailed information about their surroundings, conveying diverse features such as color, form, and movement across the visual scene. Computing these parallel spatial features requires a large and diverse network of neurons, such that in animals as distant as flies and humans, visual regions comprise half the brain's volume. These visual brain regions often reveal remarkable structure-function relationships, with neurons organized along spatial maps with shapes that directly relate to their roles in visual processing. To unravel the stunning diversity of a complex visual system, a careful mapping of the neural architecture matched to tools for targeted exploration of that circuitry is essential. Here, we report a new connectome of the right optic lobe from a male Drosophila central nervous system FIB-SEM volume and a comprehensive inventory of the fly's visual neurons. We developed a computational framework to quantify the anatomy of visual neurons, establishing a basis for interpreting how their shapes relate to spatial vision. By integrating this analysis with connectivity information, neurotransmitter identity, and expert curation, we classified the ~53,000 neurons into 727 types, about half of which are systematically described and named for the first time. Finally, we share an extensive collection of split-GAL4 lines matched to our neuron type catalog. Together, this comprehensive set of tools and data unlock new possibilities for systematic investigations of vision in Drosophila, a foundation for a deeper understanding of sensory processing.

Speaking Rate, Immediate Memory, and Grammatical Processing in Prelingual Cochlear Implant Recipients.

PURPOSE: This study examined the extent to which prelingual cochlear implant (CI) users show a slowed speaking rate compared with typical-hearing (TH) talkers when repeating various speech stimuli and whether the slowed speech of CI users relates to their immediate verbal memory. METHOD: Participants included 10 prelingually deaf teenagers who received CIs before the age of 5 years and 10 age-matched TH teenagers. Participants repeated nonword syllable strings, word strings, and center-embedded sentences, with conditions balanced for syllable length and metrical structure. Participants' digit span forward and backward scores were collected to measure immediate verbal memory. Speaking rate data were analyzed using a mixed-design, repeated-measures analysis of variance, and the relationships between speaking rate and digit spans were evaluated by Pearson correlation. RESULTS: Participants with CIs spoke more slowly than their TH peers during the sentence repetition task but not in the nonword string and word string repetition tasks. For the CI group, significant correlations emerged between speaking rate and digit span scores (both forward and backward) for the sentence repetition task but not for the nonword string or word string repetition task. For the TH group, no significant correlations were found. CONCLUSIONS: The findings indicate a relation between slowed speech production, reduced immediate verbal memory, and diminished language capabilities of prelingual CI users, particularly for syntactic processing. These results support theories claiming that immediate memory, including components of a central executive, influences the speaking rate of these talkers. Implications for therapies designed to increase speech fluency in CI recipients are discussed. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21644795.

The Role of Visibility in Silent Speech Tongue Movements: A Kinematic Study of Consonants.

Purpose To better understand the role of tongue visibility in speech, this study compared the spatiotemporal patterns of silent versus audible speech for lingual consonants of American English. Kinematic data were obtained for articulatory features assumed to be visually salient, including tongue movement (anterior displacement and midsagittal area), lip aperture, and consonant duration. Method Electromagnetic articulography was used to measure 11 native speakers' productions of five consonants (/É¡/, /w/, /ɹ/, /l/, and /ð/), selected to represent a continuum of tongue visibility. Nonword consonant-vowel syllables were elicited during a procedure designed to convey a dyadic communication environment. A method of kinematic-based consonant segmentation was developed for data processing, and results were analyzed with repeated-measures analysis of variance. Results Findings indicated increased consonant duration and lip aperture in the silent condition (vs. audible) for all five consonants. Tongue forward displacement was slightly greater in the silent condition, compared to audible, for all consonants except /É¡/, the only consonant without a visible tongue component. In addition, the extent of tongue forwarding in silent speech corresponded with the degree of tongue visibility. Conclusion During silent speech, talkers increased their lip aperture and consonant duration and tended to shift their tongues forward for the most visible lingual consonants, suggesting that talkers may be aware at some level of the need to increase articulatory visibility of the tongue in the presence of an interlocutor during adverse speech conditions.

Impact of Pre-Existing Mitral Regurgitation Following Left Ventricular Assist Device Implant.

OBJECTIVES: Optimal management of significant mitral regurgitation (SMR) during left ventricular assist device (LVAD) placement remains uncertain. This study evaluates the effect of untreated preop SMR on outcomes following LVAD implant. METHODS: Adults undergoing primary LVAD placement from April 2004 to May 2017 were included. Most recent preop transthoracic echocardiogram (TTE) was used to divide patients into an SMR group with moderate or greater regurgitation, and a group without SMR. Patients underwent LVAD implant without correction of SMR. Primary endpoint was 3-year postoperative survival, with secondary endpoints of length of stay (LOS), resolution of SMR following LVAD on postdischarge (30 day) TTE, and 1-year TTE. RESULTS: LVAD placement was performed in 270 patients, 172 (63.7%) without SMR and 98 (36.3%) with SMR. There were no differences in comorbidities including diabetes, hypertension, and renal disease. Preop ejection fraction was similar, but a higher pulmonary vascular resistance was recorded in the SMR group (3.6 vs 3.0 Wood Units, P = 0.048). There was no difference in 3-year mortality between the 2 cohorts (log-rank P = 0.0.803). The SMR group had decreased LOS (median 19.5 vs 22 days, P = 0.009). Of the 98 SMR patients, 91 (92.9%) had resolution of SMR to less than moderate at 30 days. At 1 year, 15% of those with preoperative SMR had recurrent SMR. CONCLUSIONS: Patients undergoing LVAD placement with preop SMR experience no differences in mortality, and a majority experience resolution of MR after implant. Longer-term SMR recurrence and need for mitral intervention with LVAD implant warrant further investigation.

A connectome and analysis of the adult Drosophila central brain.

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed to answer circuit questions, and provide procedures linking the neurons defined by our analysis with genetic reagents. Biologically, we examine distributions of connection strengths, neural motifs on different scales, electrical consequences of compartmentalization, and evidence that maximizing packing density is an important criterion in the evolution of the fly's brain.

Animal brains of all sizes, from the smallest to the largest, work in broadly similar ways. Studying the brain of any one animal in depth can thus reveal the general principles behind the workings of all brains. The fruit fly Drosophila is a popular choice for such research. With about 100,000 neurons ­ compared to some 86 billion in humans ­ the fly brain is small enough to study at the level of individual cells. But it nevertheless supports a range of complex behaviors, including navigation, courtship and learning. Thanks to decades of research, scientists now have a good understanding of which parts of the fruit fly brain support particular behaviors. But exactly how they do this is often unclear. This is because previous studies showing the connections between cells only covered small areas of the brain. This is like trying to understand a novel when all you can see is a few isolated paragraphs. To solve this problem, Scheffer, Xu, Januszewski, Lu, Takemura, Hayworth, Huang, Shinomiya et al. prepared the first complete map of the entire central region of the fruit fly brain. The central brain consists of approximately 25,000 neurons and around 20 million connections. To prepare the map ­ or connectome ­ the brain was cut into very thin 8nm slices and photographed with an electron microscope. A three-dimensional map of the neurons and connections in the brain was then reconstructed from these images using machine learning algorithms. Finally, Scheffer et al. used the new connectome to obtain further insights into the circuits that support specific fruit fly behaviors. The central brain connectome is freely available online for anyone to access. When used in combination with existing methods, the map will make it easier to understand how the fly brain works, and how and why it can fail to work correctly. Many of these findings will likely apply to larger brains, including our own. In the long run, studying the fly connectome may therefore lead to a better understanding of the human brain and its disorders. Performing a similar analysis on the brain of a small mammal, by scaling up the methods here, will be a likely next step along this path.

Acute In Vivo Functional Assessment of a Biodegradable Stentless Elastomeric Tricuspid Valve.

Degradable heart valves based on in situ tissue regeneration have been proposed as potentially durable and non-thrombogenic prosthetic alternatives. We evaluated the acute in vivo function, microstructure, mechanics, and thromboresistance of a stentless biodegradable tissue-engineered heart valve (TEHV) in the tricuspid position. Biomimetic stentless tricuspid valves were fabricated with poly(carbonate urethane)urea (PCUU) by double-component deposition (DCD) processing to mimic native valve mechanics and geometry. Five swine then underwent 24-h TEHV implantation in the tricuspid position. Echocardiography demonstrated good leaflet motion and no prolapse and trace to mild regurgitation in all but one animal. Histology revealed patches of proteinaceous deposits with no cellular uptake. SEM demonstrated retained scaffold microarchitecture with proteinaceous deposits but no platelet aggregation or thrombosis. Explanted PCUU leaflet thickness and mechanical anisotropy were comparable with native tricuspid leaflets. Bioinspired, elastomeric, stentless TEHVs fabricated by DCD were readily implantable and demonstrated good acute function in the tricuspid position.

Recognition of emotional prosody by Mandarin-speaking adults with cochlear implants.

To understand how cochlear implant processing affects emotional prosody recognition in tonal languages, how normal-hearing (NH) and cochlear-implanted (CI) adults identify four emotions ("angry," "happy," "sad," and "neutral") in short, semantically neutral, Mandarin sentences are compared. Depending on hearing status (CI, NH), adults heard natural speech and/or noise-vocoded speech conditions (4-, 8-, and 16-spectral channels). Results suggest that Mandarin-speaking adults with CIs recognize emotions with similar accuracy as NH listeners attending to spectrally degraded (4-channel) vocoded speech. The accuracy noted for Mandarin appears to be lower than that described in previous studies of English.

The association of imaging equipment age with other quality metrics and successful laboratory accreditation by the Intersocietal Accreditation Commission.

BACKGROUND: Intersocietal Accreditation Commission (IAC) accreditation is granted or delayed depending on the fulfillment of several quality metrics. Investing in up-to-date equipment might reflect a commitment to quality. METHODS: Data from echocardiography (n = 3079) and nuclear cardiology (n = 1835) accreditation applications submitted between 2012 and 2014 were evaluated to determine the mean age of laboratory equipment. Laboratory quality was assessed by the number of missing quality metrics, and a composite quality score was calculated as the sum of missing quality metrics. A lower score thus represented better laboratory quality. The relationship between equipment age and quality was explored as an interaction term between equipment age and the composite quality score and was incorporated into regression models for prediction of accreditation status. RESULTS: During the study period, 49% of echocardiography and 42% of nuclear laboratories were granted accreditation without delay. For both echocardiography and nuclear laboratories, there was a statistically significant trend toward an increasing number of missing quality metrics with increasing quartiles of equipment age. The interaction between equipment age and the composite quality score was a significant predictor of delay of accreditation for both echocardiography and nuclear cardiology laboratories, with a stronger association for 1st-time applicants. Among sites applying for accreditation in both modalities simultaneously, accreditation in one modality predicted the accreditation decision for the other. CONCLUSIONS: Laboratory quality is an important determinant of IAC accreditation, and equipment age is an effect modifier of this relationship. Contemporary equipment likely reflects a commitment to quality, for both echocardiography and nuclear laboratories.

Non-vitamin K oral anticoagulants versus warfarin for left atrial appendage thrombus resolution in nonvalvular atrial fibrillation or flutter.

BACKGROUND: Non-vitamin K oral anticoagulants (NOACs) have emerged as alternatives to vitamin K antagonists in select situations. For left atrial (LA) appendage thrombus in nonvalvular atrial fibrillation (AF) or flutter, guidelines recommend oral anticoagulation (OAC) for at least 3 weeks prior to reassessment. Data comparing NOACs to warfarin in this scenario are scarce. METHODS: A retrospective study identified subjects with nonvalvular AF or flutter who were: a) noted to have LA thrombus detected on transesophageal echocardiography (TEE), b) previously not receiving long-term OAC; and c) evaluated for resolution of LA thrombus by follow-up TEE between 3 weeks to less than 1 year of the initial TEE. RESULTS: The study included 45 subjects with mean age 63.2 years, 69% male, 78% white race/ethnicity, 42% paroxysmal, and mean CHA2 DS2 -VASc score 3.4 ± 1.7. All LA thrombi were confined to the appendage. OAC received included apixaban (3), dabigatran (13), rivaroxaban (6), and warfarin (23), The median follow-up time to repeat TEE was 67 (interquartile range, 49-96) days. LA appendage thrombus resolution rates were 76% for the entire cohort, 77% for NOACs, and 74% for warfarin. In univariable logistic regression analysis, LA appendage thrombus resolution was similar for NOACs when compared to warfarin (odds ratio, 1.20; 95% confidence interval, 0.31-4.69; P = .79). CONCLUSIONS: In patients nonvalvular AF or flutter who were OAC naïve at the time of diagnosis with LA appendage thrombus, complete resolution was similar between NOACs and warfarin.

DVID: Distributed Versioned Image-Oriented Dataservice.

Open-source software development has skyrocketed in part due to community tools like github.com, which allows publication of code as well as the ability to create branches and push accepted modifications back to the original repository. As the number and size of EM-based datasets increases, the connectomics community faces similar issues when we publish snapshot data corresponding to a publication. Ideally, there would be a mechanism where remote collaborators could modify branches of the data and then flexibly reintegrate results via moderated acceptance of changes. The DVID system provides a web-based connectomics API and the first steps toward such a distributed versioning approach to EM-based connectomics datasets. Through its use as the central data resource for Janelia's FlyEM team, we have integrated the concepts of distributed versioning into reconstruction workflows, allowing support for proofreader training and segmentation experiments through branched, versioned data. DVID also supports persistence to a variety of storage systems from high-speed local SSDs to cloud-based object stores, which allows its deployment on laptops as well as large servers. The tailoring of the backend storage to each type of connectomics data leads to efficient storage and fast queries. DVID is freely available as open-source software with an increasing number of supported storage options.

In vivo functional assessment of a novel degradable metal and elastomeric scaffold-based tissue engineered heart valve.

OBJECTIVE: Ideal heart valve solutions aim to provide thrombosis-free durability. A scaffold-based polycarbonate urethane urea tissue-engineered heart valve designed to mimic native valve microstructure and function was used. This study examined the acute in vivo function of a stented tissue-engineered heart valve in a porcine model. METHODS: Trileaflet valves were fabricated by electrospinning polycarbonate urethane urea using double component fiber deposition. The tissue-engineered heart valve was mounted on an AZ31 magnesium alloy biodegradable stent frame. Five 80-kg Yorkshire pigs underwent open tissue-engineered heart valve implantation on cardiopulmonary bypass in the pulmonary position. Tissue-engineered heart valve function was echocardiographically evaluated immediately postimplant and at planned study end points at 1, 4, 8, and 12 hours. Explanted valves underwent biaxial mechanical testing and scanning electron microscopy for ultrastructural analysis and thrombosis detection. RESULTS: All 5 animals underwent successful valve implantation. All were weaned from cardiopulmonary bypass, closed, and recovered until harvest study end point except 1 animal that was found to have congenital tricuspid valve dysplasia and that was euthanized postimplant. All 5 cases revealed postcardiopulmonary bypass normal leaflet function, no regurgitation, and an average peak velocity of 2 m/s, unchanged at end point. All tissue-engineered heart valve leaflets retained microstructural architecture with no platelet activation or thrombosis by scanning electron microscopy. There was microscopic evidence of fibrin deposition on 2 of 5 stent frames, not on the tissue-engineered heart valve. Biaxial stress examination revealed retained postimplant mechanics of tissue-engineered heart valve fibers without functional or ultrastructural degradation. CONCLUSIONS: A biodegradable elastomeric heart valve scaffold for in situ tissue-engineered leaflet replacement is acutely functional and devoid of leaflet microthrombosis.

Obstructive Sleep Apnea in Posttraumatic Stress Disorder Comorbid With Mood Disorder: Significantly Higher Incidence Than in Either Diagnosis Alone.

OBJECTIVE: To examine the correlations between obstructive sleep apnea (OSA) and psychiatric disorders such as major depressive disorder (MDD), posttraumatic stress disorder (PTSD), or bipolar disorder (BD) and whether comorbid psychiatric diagnosis increases the risk of OSA. METHODS: This retrospective chart review study included all patients (N = 413) seen within a randomly selected 4-month period (August 2014 to November 2014) in a Veterans Administration outpatient psychiatry clinic. Patients were screened for symptoms of OSA with the STOP-BANG Questionnaire. Those with a positive screen were referred to the sleep clinic for confirmation of the diagnosis by polysomnogram (PSG). Frequency of PSG-confirmed OSA was correlated with different psychiatric disorders and comorbid psychiatric diagnoses. RESULTS: The study showed a high prevalence of OSA in psychiatric patients, particularly with MDD (37.8%) and PTSD (35.5%) and less so with BD (16.7%). Among all patients with OSA (n = 155), those with comorbid BD and PTSD had a significantly higher rate of OSA than those with BD alone (χ² = 7.28, P < .05) but not with PTSD alone. We also found a statistically significant higher incidence of OSA in male veterans with either MDD comorbid with PTSD (χ² = 3.869, P < .05) or BD comorbid with PTSD (χ² = 6.631, P < .05) compared with either mood disorder or PTSD alone. CONCLUSIONS: The study showed a high prevalence of OSA in psychiatric patients, particularly in those with PTSD and MDD and less so with BD. There was a statistically significant increase in the incidence of OSA in male veterans with either BD with comorbid PTSD or MDD with comorbid PTSD.​​.

Oral anticoagulation and left atrial thrombi resolution in nonrheumatic atrial fibrillation or flutter: A systematic review and meta-analysis.

BACKGROUND: Oral anticoagulation (OAC) is prescribed for left atrial thrombi (LAT) in nonrheumatic atrial fibrillation (AF) and/or atrial flutter (AFL). The study objective was to review the existing evidence regarding LAT resolution in nonrheumatic AF and/or AFL with OAC agents. METHODS: Data sources included PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) between January 1, 1991 and February 10, 2017. English-language studies that assessed LAT resolution with OAC agents in subjects with nonrheumatic AF and/or AFL, by serial transesophageal echocardiography, and with follow-up times ≥ 3 weeks and < 1 year, were selected. Study quality was assessed using recommendations adapted from the Agency for Healthcare Research and Quality. Pooled LAT resolution rates were evaluated for vitamin K antagonist (VKA) studies and low risk of bias warfarin studies. RESULTS: The pooled LAT resolution rate of 619 subjects from 16 VKA studies was 63.7% (95% confidence interval [CI], 53.3%-72.9%). The pooled LAT resolution rate of 94 subjects from four studies that specified warfarin use, exclusion of prior long-term therapeutic OAC, and target international normalized ratio (INR) ≥ 2.0 and/or average achieved INR ≥ 2.0 was 79.3% (95% CI, 69.8%-86.4%). Two studies in direct-acting oral anticoagulants (DOACs) reported LAT resolution rates of 89.5% (17 of 19) for dabigatran and 41.5% (22 of 53) for rivaroxaban. CONCLUSIONS: Warfarin is the most studied initial OAC agent for treating LAT in nonrheumatic AF and/or AFL with a resolution rate of nearly 80%. Further studies in DOACs are warranted.

Outcomes of persistent pulmonary hypertension following transcatheter aortic valve replacement.

OBJECTIVES: To determine the prevalence and factors associated with persistent pulmonary hypertension (PH) following transcatheter aortic valve replacement (TAVR) and its relationship with long-term mortality. METHODS: Consecutive patients who underwent TAVR from July 2011 through January 2016 were studied. The prevalence of baseline PH (mean pulmonary artery pressure ≥25 mm Hg on right heart catheterisation) and the prevalence and the predictors of persistent≥moderate PH (pulmonary artery systolic pressure (PASP)>45 mm Hg on 1 month post-TAVR transthoracic Doppler echocardiography) were collected. Cox models quantified the effect of persistent PH on subsequent mortality while adjusting for confounders. RESULTS: Of the 407 TAVR patients, 273 (67%) had PH at baseline. Of these, 102 (25%) had persistent≥moderate PH. Mortality at 2 years in patients with no baseline PH versus those with PH improvement (follow-up PASP≤45 mm Hg) versus those with persistent≥moderate PH was 15.4%, 16.6% and 31.3%, respectively (p=0.049). After adjusting for Society of Thoracic Surgeons Predicted Risk of Mortality and baseline right ventricular function (using tricuspid annular plane systolic excursion), persistent≥moderate PH remained associated with all-cause mortality (HR=1.82, 95% CI 1.06 to 3.12, p=0.03). Baseline characteristics associated with increased likelihood of persistent≥moderate PH were ≥moderate tricuspid regurgitation, ≥moderate mitral regurgitation, atrial fibrillation/flutter, early (E) to late (A) ventricular filling velocities (E/A ratio) and left atrial volume index. CONCLUSIONS: Persistency of even moderate or greater PH at 1 month post-TAVR is common and associated with higher all-cause mortality.

A connectome of a learning and memory center in the adult Drosophila brain.

Understanding memory formation, storage and retrieval requires knowledge of the underlying neuronal circuits. In Drosophila, the mushroom body (MB) is the major site of associative learning. We reconstructed the morphologies and synaptic connections of all 983 neurons within the three functional units, or compartments, that compose the adult MB's α lobe, using a dataset of isotropic 8 nm voxels collected by focused ion-beam milling scanning electron microscopy. We found that Kenyon cells (KCs), whose sparse activity encodes sensory information, each make multiple en passant synapses to MB output neurons (MBONs) in each compartment. Some MBONs have inputs from all KCs, while others differentially sample sensory modalities. Only 6% of KC>MBON synapses receive a direct synapse from a dopaminergic neuron (DAN). We identified two unanticipated classes of synapses, KC>DAN and DAN>MBON. DAN activation produces a slow depolarization of the MBON in these DAN>MBON synapses and can weaken memory recall.

Using electromagnetic articulography with a tongue lateral sensor to discriminate manner of articulation.

This study examined the contributions of the tongue tip (TT), tongue body (TB), and tongue lateral (TL) sensors in the electromagnetic articulography (EMA) measurement of American English alveolar consonants. Thirteen adults produced /ɹ/, /l/, /z/, and /d/ in /ɑCɑ/ syllables while being recorded with an EMA system. According to statistical analysis of sensor movement and the results of a machine classification experiment, the TT sensor contributed most to consonant differences, followed by TB. The TL sensor played a complementary role, particularly for distinguishing /z/.

Echocardiographic evaluation and guidance for MitraClip procedure.

Transcatheter mitral valve repair using the MitraClip system (Abbott, Abbott Park, Il, USA) has become a world-wide, well-established therapeutic alternative to treat symptomatic patients with severe mitral regurgitation and prohibitive surgical risk. This article offers a comprehensive review of the important clinical and imaging aspects related to the patient selection, imaging evaluation and intraprocedural guidance for optimal results using this transcatheter device therapy. This article provides an updated framework for the interested practitioners summarizing the current understanding and applications for this device based on the current literature and growing experience of this technique.