RESUMEN
The evolution and development of the head have long captivated researchers due to the crucial role of the head as the gateway for sensory stimuli and the intricate structural complexity of the head. Although significant progress has been made in understanding head development in various vertebrate species, our knowledge of early human head ontogeny remains limited. Here, we used advanced whole-mount immunostaining and 3D imaging techniques to generate a comprehensive 3D cellular atlas of human head embryogenesis. We present detailed developmental series of diverse head tissues and cell types, including muscles, vasculature, cartilage, peripheral nerves, and exocrine glands. These datasets, accessible through a dedicated web interface, provide insights into human embryogenesis. We offer perspectives on the branching morphogenesis of human exocrine glands and unknown features of the development of neurovascular and skeletomuscular structures. These insights into human embryology have important implications for understanding craniofacial defects and neurological disorders and advancing diagnostic and therapeutic strategies.
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Embrión de Mamíferos , Cabeza , Humanos , Morfogénesis , Cabeza/crecimiento & desarrolloRESUMEN
Many animals can navigate toward a goal they cannot see based on an internal representation of that goal in the brain's spatial maps. These maps are organized around networks with stable fixed-point dynamics (attractors), anchored to landmarks, and reciprocally connected to motor control. This review summarizes recent progress in understanding these networks, focusing on studies in arthropods. One factor driving recent progress is the availability of the Drosophila connectome; however, it is increasingly clear that navigation depends on ongoing synaptic plasticity in these networks. Functional synapses appear to be continually reselected from the set of anatomical potential synapses based on the interaction of Hebbian learning rules, sensory feedback, attractor dynamics, and neuromodulation. This can explain how the brain's maps of space are rapidly updated; it may also explain how the brain can initialize goals as stable fixed points for navigation.
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Conectoma , Redes Neurales de la Computación , Animales , Aprendizaje , Encéfalo , Cabeza , Modelos NeurológicosRESUMEN
Neuronal signals that are relevant for spatial navigation have been described in many species1-10. However, a circuit-level understanding of how such signals interact to guide navigational behaviour is lacking. Here we characterize a neuronal circuit in the Drosophila central complex that compares internally generated estimates of the heading and goal angles of the fly-both of which are encoded in world-centred (allocentric) coordinates-to generate a body-centred (egocentric) steering signal. Past work has suggested that the activity of EPG neurons represents the fly's moment-to-moment angular orientation, or heading angle, during navigation2,11. An animal's moment-to-moment heading angle, however, is not always aligned with its goal angle-that is, the allocentric direction in which it wishes to progress forward. We describe FC2 cells12, a second set of neurons in the Drosophila brain with activity that correlates with the fly's goal angle. Focal optogenetic activation of FC2 neurons induces flies to orient along experimenter-defined directions as they walk forward. EPG and FC2 neurons connect monosynaptically to a third neuronal class, PFL3 cells12,13. We found that individual PFL3 cells show conjunctive, spike-rate tuning to both the heading angle and the goal angle during goal-directed navigation. Informed by the anatomy and physiology of these three cell classes, we develop a model that explains how this circuit compares allocentric heading and goal angles to build an egocentric steering signal in the PFL3 output terminals. Quantitative analyses and optogenetic manipulations of PFL3 activity support the model. Finally, using a new navigational memory task, we show that flies expressing disruptors of synaptic transmission in subsets of PFL3 cells have a reduced ability to orient along arbitrary goal directions, with an effect size in quantitative accordance with the prediction of our model. The biological circuit described here reveals how two population-level allocentric signals are compared in the brain to produce an egocentric output signal that is appropriate for motor control.
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Encéfalo , Drosophila melanogaster , Objetivos , Cabeza , Vías Nerviosas , Orientación Espacial , Navegación Espacial , Animales , Potenciales de Acción , Encéfalo/citología , Encéfalo/fisiología , Drosophila melanogaster/citología , Drosophila melanogaster/fisiología , Cabeza/fisiología , Locomoción , Neuronas/metabolismo , Optogenética , Orientación Espacial/fisiología , Percepción Espacial/fisiología , Memoria Espacial/fisiología , Navegación Espacial/fisiología , Transmisión SinápticaRESUMEN
To navigate, we must continuously estimate the direction we are headed in, and we must correct deviations from our goal1. Direction estimation is accomplished by ring attractor networks in the head direction system2,3. However, we do not fully understand how the sense of direction is used to guide action. Drosophila connectome analyses4,5 reveal three cell populations (PFL3R, PFL3L and PFL2) that connect the head direction system to the locomotor system. Here we use imaging, electrophysiology and chemogenetic stimulation during navigation to show how these populations function. Each population receives a shifted copy of the head direction vector, such that their three reference frames are shifted approximately 120° relative to each other. Each cell type then compares its own head direction vector with a common goal vector; specifically, it evaluates the congruence of these vectors via a nonlinear transformation. The output of all three cell populations is then combined to generate locomotor commands. PFL3R cells are recruited when the fly is oriented to the left of its goal, and their activity drives rightward turning; the reverse is true for PFL3L. Meanwhile, PFL2 cells increase steering speed, and are recruited when the fly is oriented far from its goal. PFL2 cells adaptively increase the strength of steering as directional error increases, effectively managing the tradeoff between speed and accuracy. Together, our results show how a map of space in the brain can be combined with an internal goal to generate action commands, via a transformation from world-centric coordinates to body-centric coordinates.
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Encéfalo , Drosophila melanogaster , Objetivos , Cabeza , Neuronas , Orientación Espacial , Navegación Espacial , Animales , Encéfalo/citología , Encéfalo/fisiología , Conectoma , Drosophila melanogaster/citología , Drosophila melanogaster/fisiología , Cabeza/fisiología , Locomoción/fisiología , Neuronas/clasificación , Neuronas/fisiología , Orientación Espacial/fisiología , Navegación Espacial/fisiología , Factores de TiempoRESUMEN
Motor neurons are the final common pathway1 through which the brain controls movement of the body, forming the basic elements from which all movement is composed. Yet how a single motor neuron contributes to control during natural movement remains unclear. Here we anatomically and functionally characterize the individual roles of the motor neurons that control head movement in the fly, Drosophila melanogaster. Counterintuitively, we find that activity in a single motor neuron rotates the head in different directions, depending on the starting posture of the head, such that the head converges towards a pose determined by the identity of the stimulated motor neuron. A feedback model predicts that this convergent behaviour results from motor neuron drive interacting with proprioceptive feedback. We identify and genetically2 suppress a single class of proprioceptive neuron3 that changes the motor neuron-induced convergence as predicted by the feedback model. These data suggest a framework for how the brain controls movements: instead of directly generating movement in a given direction by activating a fixed set of motor neurons, the brain controls movements by adding bias to a continuing proprioceptive-motor loop.
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Drosophila melanogaster , Neuronas Motoras , Movimiento , Postura , Propiocepción , Animales , Drosophila melanogaster/anatomía & histología , Drosophila melanogaster/genética , Drosophila melanogaster/fisiología , Retroalimentación Fisiológica/fisiología , Cabeza/fisiología , Modelos Neurológicos , Neuronas Motoras/fisiología , Movimiento/fisiología , Postura/fisiología , Propiocepción/genética , Propiocepción/fisiología , MasculinoRESUMEN
Indirect development with an intermediate larva exists in all major animal lineages1, which makes larvae central to most scenarios of animal evolution2-11. Yet how larvae evolved remains disputed. Here we show that temporal shifts (that is, heterochronies) in trunk formation underpin the diversification of larvae and bilaterian life cycles. We performed chromosome-scale genome sequencing in the annelid Owenia fusiformis with transcriptomic and epigenomic profiling during the life cycles of this and two other annelids. We found that trunk development is deferred to pre-metamorphic stages in the feeding larva of O. fusiformis but starts after gastrulation in the non-feeding larva with gradual metamorphosis of Capitella teleta and the direct developing embryo of Dimorphilus gyrociliatus. Accordingly, the embryos of O. fusiformis develop first into an enlarged anterior domain that forms larval tissues and the adult head12. Notably, this also occurs in the so-called 'head larvae' of other bilaterians13-17, with which the O. fusiformis larva shows extensive transcriptomic similarities. Together, our findings suggest that the temporal decoupling of head and trunk formation, as maximally observed in head larvae, facilitated larval evolution in Bilateria. This diverges from prevailing scenarios that propose either co-option9,10 or innovation11 of gene regulatory programmes to explain larva and adult origins.
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Genómica , Estadios del Ciclo de Vida , Poliquetos , Animales , Larva/anatomía & histología , Larva/crecimiento & desarrollo , Poliquetos/anatomía & histología , Poliquetos/embriología , Poliquetos/genética , Poliquetos/crecimiento & desarrollo , Perfilación de la Expresión Génica , Epigenómica , Cabeza/anatomía & histología , Cabeza/embriología , Cabeza/crecimiento & desarrolloRESUMEN
The head direction (HD) system functions as the brain's internal compass1,2, classically formalized as a one-dimensional ring attractor network3,4. In contrast to a globally consistent magnetic compass, the HD system does not have a universal reference frame. Instead, it anchors to local cues, maintaining a stable offset when cues rotate5-8 and drifting in the absence of referents5,8-10. However, questions about the mechanisms that underlie anchoring and drift remain unresolved and are best addressed at the population level. For example, the extent to which the one-dimensional description of population activity holds under conditions of reorientation and drift is unclear. Here we performed population recordings of thalamic HD cells using calcium imaging during controlled rotations of a visual landmark. Across experiments, population activity varied along a second dimension, which we refer to as network gain, especially under circumstances of cue conflict and ambiguity. Activity along this dimension predicted realignment and drift dynamics, including the speed of network realignment. In the dark, network gain maintained a 'memory trace' of the previously displayed landmark. Further experiments demonstrated that the HD network returned to its baseline orientation after brief, but not longer, exposures to a rotated cue. This experience dependence suggests that memory of previous associations between HD neurons and allocentric cues is maintained and influences the internal HD representation. Building on these results, we show that continuous rotation of a visual landmark induced rotation of the HD representation that persisted in darkness, demonstrating experience-dependent recalibration of the HD system. Finally, we propose a computational model to formalize how the neural compass flexibly adapts to changing environmental cues to maintain a reliable representation of HD. These results challenge classical one-dimensional interpretations of the HD system and provide insights into the interactions between this system and the cues to which it anchors.
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Señales (Psicología) , Cabeza , Neuronas , Orientación , Tálamo , Señalización del Calcio , Cabeza/fisiología , Neuronas/citología , Neuronas/fisiología , Orientación/fisiología , Orientación Espacial/fisiología , Rotación , Tálamo/citología , Tálamo/fisiologíaRESUMEN
Recent success in training artificial agents and robots derives from a combination of direct learning of behavioural policies and indirect learning through value functions1-3. Policy learning and value learning use distinct algorithms that optimize behavioural performance and reward prediction, respectively. In animals, behavioural learning and the role of mesolimbic dopamine signalling have been extensively evaluated with respect to reward prediction4; however, so far there has been little consideration of how direct policy learning might inform our understanding5. Here we used a comprehensive dataset of orofacial and body movements to understand how behavioural policies evolved as naive, head-restrained mice learned a trace conditioning paradigm. Individual differences in initial dopaminergic reward responses correlated with the emergence of learned behavioural policy, but not the emergence of putative value encoding for a predictive cue. Likewise, physiologically calibrated manipulations of mesolimbic dopamine produced several effects inconsistent with value learning but predicted by a neural-network-based model that used dopamine signals to set an adaptive rate, not an error signal, for behavioural policy learning. This work provides strong evidence that phasic dopamine activity can regulate direct learning of behavioural policies, expanding the explanatory power of reinforcement learning models for animal learning6.
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Conducta Animal , Dopamina , Aprendizaje , Vías Nerviosas , Refuerzo en Psicología , Animales , Ratones , Algoritmos , Dopamina/metabolismo , Redes Neurales de la Computación , Recompensa , Conjuntos de Datos como Asunto , Señales (Psicología) , Condicionamiento Psicológico , Movimiento , CabezaRESUMEN
The nucleolus is the most prominent membraneless condensate in the nucleus. It comprises hundreds of proteins with distinct roles in the rapid transcription of ribosomal RNA (rRNA) and efficient processing within units comprising a fibrillar centre and a dense fibrillar component and ribosome assembly in a granular component1. The precise localization of most nucleolar proteins and whether their specific localization contributes to the radial flux of pre-rRNA processing have remained unknown owing to insufficient resolution in imaging studies2-5. Therefore, how these nucleolar proteins are functionally coordinated with stepwise pre-rRNA processing requires further investigation. Here we screened 200 candidate nucleolar proteins using high-resolution live-cell microscopy and identified 12 proteins that are enriched towards the periphery of the dense fibrillar component (PDFC). Among these proteins, unhealthy ribosome biogenesis 1 (URB1) is a static, nucleolar protein that ensures 3' end pre-rRNA anchoring and folding for U8 small nucleolar RNA recognition and the subsequent removal of the 3' external transcribed spacer (ETS) at the dense fibrillar component-PDFC boundary. URB1 depletion leads to a disrupted PDFC, uncontrolled pre-rRNA movement, altered pre-rRNA conformation and retention of the 3' ETS. These aberrant 3' ETS-attached pre-rRNA intermediates activate exosome-dependent nucleolar surveillance, resulting in decreased 28S rRNA production, head malformations in zebrafish and delayed embryonic development in mice. This study provides insight into functional sub-nucleolar organization and identifies a physiologically essential step in rRNA maturation that requires the static protein URB1 in the phase-separated nucleolus.
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Nucléolo Celular , Exosomas , Precursores del ARN , Procesamiento Postranscripcional del ARN , ARN Ribosómico , Pez Cebra , Animales , Ratones , Nucléolo Celular/metabolismo , Desarrollo Embrionario , Exosomas/metabolismo , Cabeza/anomalías , Microscopía , Proteínas Nucleares/metabolismo , Precursores del ARN/metabolismo , ARN Ribosómico/genética , ARN Ribosómico/metabolismo , ARN Ribosómico 28S/metabolismo , Pez Cebra/genética , Pez Cebra/metabolismoRESUMEN
Many animals use an internal sense of direction to guide their movements through the world. Neurons selective to head direction are thought to support this directional sense and have been found in a diverse range of species, from insects to primates, highlighting their evolutionary importance. Across species, most head-direction networks share four key properties: a unique representation of direction at all times, persistent activity in the absence of movement, integration of angular velocity to update the representation, and the use of directional cues to correct drift. The dynamics of theorized network structures called ring attractors elegantly account for these properties, but their relationship to brain circuits is unclear. Here, we review experiments in rodents and flies that offer insights into potential neural implementations of ring attractor networks. We suggest that a theory-guided search across model systems for biological mechanisms that enable such dynamics would uncover general principles underlying head-direction circuit function.
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Cabeza/fisiología , Neuronas/fisiología , Orientación/fisiología , Percepción Espacial/fisiología , Potenciales de Acción/fisiología , Animales , Humanos , Modelos NeurológicosRESUMEN
Many behavioural tasks require the manipulation of mathematical vectors, but, outside of computational models1-7, it is not known how brains perform vector operations. Here we show how the Drosophila central complex, a region implicated in goal-directed navigation7-10, performs vector arithmetic. First, we describe a neural signal in the fan-shaped body that explicitly tracks the allocentric travelling angle of a fly, that is, the travelling angle in reference to external cues. Past work has identified neurons in Drosophila8,11-13 and mammals14 that track the heading angle of an animal referenced to external cues (for example, head direction cells), but this new signal illuminates how the sense of space is properly updated when travelling and heading angles differ (for example, when walking sideways). We then characterize a neuronal circuit that performs an egocentric-to-allocentric (that is, body-centred to world-centred) coordinate transformation and vector addition to compute the allocentric travelling direction. This circuit operates by mapping two-dimensional vectors onto sinusoidal patterns of activity across distinct neuronal populations, with the amplitude of the sinusoid representing the length of the vector and its phase representing the angle of the vector. The principles of this circuit may generalize to other brains and to domains beyond navigation where vector operations or reference-frame transformations are required.
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Encéfalo/fisiología , Señales (Psicología) , Drosophila melanogaster/fisiología , Matemática , Modelos Neurológicos , Memoria Espacial/fisiología , Navegación Espacial/fisiología , Animales , Encéfalo/citología , Drosophila melanogaster/citología , Femenino , Vuelo Animal , Objetivos , Cabeza/fisiología , Neuronas/fisiología , Percepción Espacial/fisiología , CaminataRESUMEN
When an animal moves through the world, its brain receives a stream of information about the body's translational velocity from motor commands and sensory feedback signals. These incoming signals are referenced to the body, but ultimately, they must be transformed into world-centric coordinates for navigation1,2. Here we show that this computation occurs in the fan-shaped body in the brain of Drosophila melanogaster. We identify two cell types, PFNd and PFNv3-5, that conjunctively encode translational velocity and heading as a fly walks. In these cells, velocity signals are acquired from locomotor brain regions6 and are multiplied with heading signals from the compass system. PFNd neurons prefer forward-ipsilateral movement, whereas PFNv neurons prefer backward-contralateral movement, and perturbing PFNd neurons disrupts idiothetic path integration in walking flies7. Downstream, PFNd and PFNv neurons converge onto hΔB neurons, with a connectivity pattern that pools together heading and translation direction combinations corresponding to the same movement in world-centric space. This network motif effectively performs a rotation of the brain's representation of body-centric translational velocity according to the current heading direction. Consistent with our predictions, we observe that hΔB neurons form a representation of translational velocity in world-centric coordinates. By integrating this representation over time, it should be possible for the brain to form a working memory of the path travelled through the environment8-10.
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Encéfalo/fisiología , Drosophila melanogaster/fisiología , Locomoción/fisiología , Modelos Neurológicos , Percepción Espacial/fisiología , Memoria Espacial/fisiología , Navegación Espacial/fisiología , Animales , Encéfalo/citología , Drosophila melanogaster/citología , Femenino , Cabeza , Memoria a Corto Plazo , Inhibición Neural , Vías Nerviosas , Neuronas/fisiología , Rotación , Factores de Tiempo , CaminataRESUMEN
Most animals have compound eyes, with tens to thousands of lenses attached rigidly to the exoskeleton. A natural assumption is that all of these species must resort to moving either their head or their body to actively change their visual input. However, classic anatomy has revealed that flies have muscles poised to move their retinas under the stable lenses of each compound eye1-3. Here we show that Drosophila use their retinal muscles to smoothly track visual motion, which helps to stabilize the retinal image, and also to perform small saccades when viewing a stationary scene. We show that when the retina moves, visual receptive fields shift accordingly, and that even the smallest retinal saccades activate visual neurons. Using a head-fixed behavioural paradigm, we find that Drosophila perform binocular, vergence movements of their retinas-which could enhance depth perception-when crossing gaps, and impairing the physiology of retinal motor neurons alters gap-crossing trajectories during free behaviour. That flies evolved an ability to actuate their retinas suggests that moving the eye independently of the head is broadly paramount for animals. The similarities of smooth and saccadic movements of the Drosophila retina and the vertebrate eye highlight a notable example of convergent evolution.
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Drosophila , Movimientos Oculares , Músculos , Retina , Visión Ocular , Animales , Drosophila/fisiología , Movimientos Oculares/fisiología , Músculos/fisiología , Retina/fisiología , Movimientos Sacádicos/fisiología , Visión Ocular/fisiología , Visión Binocular , Percepción de Profundidad , Neuronas Motoras , Cabeza/fisiología , Drosophila melanogaster/fisiología , Evolución BiológicaRESUMEN
How the activities of large neural populations are integrated in the brain to ensure accurate perception and behavior remains a central problem in systems neuroscience. Here, we investigated population coding of naturalistic self-motion by neurons within early vestibular pathways in rhesus macaques (Macacca mulatta). While vestibular neurons displayed similar dynamic tuning to self-motion, inspection of their spike trains revealed significant heterogeneity. Further analysis revealed that, during natural but not artificial stimulation, heterogeneity resulted primarily from variability across neurons as opposed to trial-to-trial variability. Interestingly, vestibular neurons displayed different correlation structures during naturalistic and artificial self-motion. Specifically, while correlations due to the stimulus (i.e., signal correlations) did not differ, correlations between the trial-to-trial variabilities of neural responses (i.e., noise correlations) were instead significantly positive during naturalistic but not artificial stimulation. Using computational modeling, we show that positive noise correlations during naturalistic stimulation benefits information transmission by heterogeneous vestibular neural populations. Taken together, our results provide evidence that neurons within early vestibular pathways are adapted to the statistics of natural self-motion stimuli at the population level. We suggest that similar adaptations will be found in other systems and species.
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Macaca mulatta , Movimiento , Neuronas , Núcleos Vestibulares , Animales , Femenino , Potenciales de Acción , Cabeza , Modelos Neurológicos , Percepción de Movimiento , Movimiento/fisiología , Neuronas/fisiología , Núcleos Vestibulares/citología , Núcleos Vestibulares/fisiología , Masculino , Macaca mulatta/fisiologíaRESUMEN
Secreted Wnt morphogens are signaling molecules essential for embryogenesis, pathogenesis, and regeneration and require distinct modifications for secretion, gradient formation, and activity. Whether Wnt proteins can be posttranslationally inactivated during development and homeostasis is unknown. Here we identify, through functional cDNA screening, a transmembrane protein Tiki1 that is expressed specifically in the dorsal Spemann-Mangold Organizer and is required for anterior development during Xenopus embryogenesis. Tiki1 antagonizes Wnt function in embryos and human cells via a TIKI homology domain that is conserved from bacteria to mammals and acts likely as a protease to cleave eight amino-terminal residues of a Wnt protein, resulting in oxidized Wnt oligomers that exhibit normal secretion but minimized receptor-binding capability. Our findings identify a Wnt-specific protease that controls head formation, reveal a mechanism for morphogen inactivation through proteolysis-induced oxidation-oligomerization, and suggest a role of the Wnt amino terminus in evasion of oxidizing inactivation. TIKI proteins may represent potential therapeutic targets.
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Tipificación del Cuerpo , Cabeza/embriología , Proteínas de la Membrana/metabolismo , Metaloproteasas/metabolismo , Vía de Señalización Wnt , Proteínas de Xenopus/metabolismo , Xenopus/embriología , Secuencia de Aminoácidos , Animales , Embrión no Mamífero/metabolismo , Regulación del Desarrollo de la Expresión Génica , Células HEK293 , Células HeLa , Humanos , Proteínas de la Membrana/genética , Metaloproteasas/genética , Datos de Secuencia Molecular , Organizadores Embrionarios/metabolismo , Alineación de Secuencia , Xenopus/metabolismo , Proteínas de Xenopus/genéticaRESUMEN
Fine root lifespan is a critical trait associated with contrasting root strategies of resource acquisition and protection. Yet, its position within the multidimensional "root economics space" synthesizing global root economics strategies is largely uncertain, and it is rarely represented in frameworks integrating plant trait variations. Here, we compiled the most comprehensive dataset of absorptive median root lifespan (MRL) data including 98 observations from 79 woody species using (mini-)rhizotrons across 40 sites and linked MRL to other plant traits to address questions of the regulators of MRL at large spatial scales. We demonstrate that MRL not only decreases with plant investment in root nitrogen (associated with more metabolically active tissues) but also increases with construction of larger diameter roots which is often associated with greater plant reliance on mycorrhizal symbionts. Although theories linking organ structure and function suggest that root traits should play a role in modulating MRL, we found no correlation between root traits associated with structural defense (root tissue density and specific root length) and MRL. Moreover, fine root and leaf lifespan were globally unrelated, except among evergreen species, suggesting contrasting evolutionary selection between leaves and roots facing contrasting environmental influences above vs. belowground. At large geographic scales, MRL was typically longer at sites with lower mean annual temperature and higher mean annual precipitation. Overall, this synthesis uncovered several key ecophysiological covariates and environmental drivers of MRL, highlighting broad avenues for accurate parametrization of global biogeochemical models and the understanding of ecosystem response to global climate change.
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Ecosistema , Longevidad , Evolución Biológica , Cambio Climático , CabezaRESUMEN
BACKGROUND: Local injections of botulinum toxin type A have been used to treat essential head tremor but have not been extensively studied in randomized trials. METHODS: In a multicenter, double-blind, randomized trial, we assigned, in a 1:1 ratio, adult patients with essential or isolated head tremor to receive botulinum toxin type A or placebo. Botulinum toxin or placebo was injected under electromyographic guidance into each splenius capitis muscle on the day of randomization (day 0) and during week 12. The primary outcome was improvement by at least 2 points on the Clinical Global Impression of Change (CGI) scale at week 6 after the second injection (week 18 after randomization). The CGI scale was used to record the patient's assessment of the degree of improvement or worsening of head tremor since baseline; scores range from 3 (very much improved) to -3 (very much worse). Secondary outcomes included changes in tremor characteristics from baseline to weeks 6, 12, and 24. RESULTS: A total of 120 patients were enrolled; 3 patients were excluded during screening, and 117 patients were randomly assigned to receive botulinum toxin (62 patients) or placebo (55 patients) and were included in the intention-to-treat analysis. Twelve patients in the botulinum toxin group and 2 patients in the placebo group did not receive injections during week 12. The primary outcome - improvement by at least 2 points on the CGI scale at week 18 - was met by 31% of the patients in the botulinum toxin group as compared with 9% of those in the placebo group (relative risk, 3.37; 95% confidence interval, 1.35 to 8.42; P = 0.009). Analyses of secondary outcomes at 6 and 12 weeks but not at 24 weeks were generally supportive of the primary-outcome analysis. Adverse events occurred in approximately half the patients in the botulinum toxin group and included head and neck pain, posterior cervical weakness, and dysphagia. CONCLUSIONS: Injection of botulinum toxin into each splenius capitis muscle on day 0 and during week 12 was more effective than placebo in reducing the severity of isolated or essential head tremor at 18 weeks but not at 24 weeks, when the effects of injection might be expected to wane, and was associated with adverse events. (Funded by the French Ministry of Health; Btx-HT ClinicalTrials.gov number, NCT02555982.).
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Toxinas Botulínicas Tipo A , Temblor Esencial , Fármacos Neuromusculares , Temblor , Adulto , Humanos , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/efectos adversos , Toxinas Botulínicas Tipo A/uso terapéutico , Método Doble Ciego , Temblor Esencial/tratamiento farmacológico , Cabeza , Resultado del Tratamiento , Temblor/tratamiento farmacológico , Electromiografía/métodos , Inyecciones Intramusculares/métodos , Cefalea/inducido químicamente , Dolor de Cuello/inducido químicamente , Fármacos Neuromusculares/administración & dosificación , Fármacos Neuromusculares/efectos adversos , Fármacos Neuromusculares/uso terapéuticoRESUMEN
To increase granularity in human neuroimaging science, we designed and built a next-generation 7 Tesla magnetic resonance imaging scanner to reach ultra-high resolution by implementing several advances in hardware. To improve spatial encoding and increase the image signal-to-noise ratio, we developed a head-only asymmetric gradient coil (200 mT m-1, 900 T m-1s-1) with an additional third layer of windings. We integrated a 128-channel receiver system with 64- and 96-channel receiver coil arrays to boost signal in the cerebral cortex while reducing g-factor noise to enable higher accelerations. A 16-channel transmit system reduced power deposition and improved image uniformity. The scanner routinely performs functional imaging studies at 0.35-0.45 mm isotropic spatial resolution to reveal cortical layer functional activity, achieves high angular resolution in diffusion imaging and reduces acquisition time for both functional and structural imaging.
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Encéfalo , Imagen por Resonancia Magnética , Humanos , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Imagen por Resonancia Magnética/métodos , Cabeza , Neuroimagen , Relación Señal-RuidoRESUMEN
The phylum of annelids is one of the most disparate animal phyla and encompasses ambush predators, suspension feeders and terrestrial earthworms1. The early evolution of annelids remains obscure or controversial2,3, partly owing to discordance between molecular phylogenies and fossils2,4. Annelid fossils from the Cambrian period have morphologies that indicate epibenthic lifestyles, whereas phylogenomics recovers sessile, infaunal and tubicolous taxa as an early diverging grade5. Magelonidae and Oweniidae (Palaeoannelida1) are the sister group of all other annelids but contrast with Cambrian taxa in both lifestyle and gross morphology2,6. Here we describe a new fossil polychaete (bristle worm) from the early Cambrian Canglangpu formation7 that we name Dannychaeta tucolus, which is preserved within delicate, dwelling tubes that were originally organic. The head has a well-defined spade-shaped prostomium with elongated ventrolateral palps. The body has a wide, stout thorax and elongated abdomen with biramous parapodia with parapodial lamellae. This character combination is shared with extant Magelonidae, and phylogenetic analyses recover Dannychaeta within Palaeoannelida. To our knowledge, Dannychaeta is the oldest polychaete that unambiguously belongs to crown annelids, providing a constraint on the tempo of annelid evolution and revealing unrecognized ecological and morphological diversity in ancient annelids.
Asunto(s)
Fósiles , Filogenia , Poliquetos/clasificación , Abdomen/anatomía & histología , Animales , China , Cabeza/anatomía & histología , Poliquetos/anatomía & histologíaRESUMEN
Resolving the early evolution of euarthropods is one of the most challenging problems in metazoan evolution1,2. Exceptionally preserved fossils from the Cambrian period have contributed important palaeontological data to deciphering this evolutionary process3,4. Phylogenetic studies have resolved Radiodonta (also known as anomalocaridids) as the closest group to all euarthropods that have frontalmost appendages on the second head segment (Deuteropoda)5-9. However, the interrelationships among major Cambrian euarthropod groups remain disputed1,2,4,7, which impedes our understanding of the evolutionary gap between Radiodonta and Deuteropoda. Here we describe Kylinxia zhangi gen. et. sp. nov., a euarthropod from the early Cambrian Chengjiang biota of China. Kylinxia possesses not only deuteropod characteristics such as a fused head shield, a fully arthrodized trunk and jointed endopodites, but also five eyes (as in Opabinia) as well as radiodont-like raptorial frontalmost appendages. Our phylogenetic reconstruction recovers Kylinxia as a transitional taxon that bridges Radiodonta and Deuteropoda. The most basal deuteropods are retrieved as a paraphyletic lineage that features plesiomorphic raptorial frontalmost appendages and includes Kylinxia, megacheirans, panchelicerates, 'great-appendage' bivalved euarthropods and isoxyids. This phylogenetic topology supports the idea that the radiodont and megacheiran frontalmost appendages are homologous, that the chelicerae of Chelicerata originated from megacheiran great appendages and that the sensorial antennae in Mandibulata derived from ancestral raptorial forms. Kylinxia thus provides important insights into the phylogenetic relationships among early euarthropods, the evolutionary transformations and disparity of frontalmost appendages, and the origin of crucial evolutionary innovations in this clade.