Autonomous Robotic Drilling System for Mice Cranial Window Creation: An Evaluation with an Egg Model

Robotic assistance for experimental manipulation in the life sciences is expected to enable precise manipulation of valuable samples, regardless of the skill of the scientist. Experimental specimens in the life sciences are subject to individual variability and deformation, and therefore require autonomous robotic control. As an example, we are studying the installation of a cranial window in a mouse. This operation requires the removal of the skull, which is approximately 300 um thick, to cut it into a circular shape 8 mm in diameter, but the shape of the mouse skull varies depending on the strain of mouse, sex and week of age. The thickness of the skull is not uniform, with some areas being thin and others thicker. It is also difficult to ensure that the skulls of the mice are kept in the same position for each operation. It is not realistically possible to measure all these features and pre-program a robotic trajectory for individual mice. The paper therefore proposes an autonomous robotic drilling method. The proposed method consists of drilling trajectory planning and image-based task completion level recognition. The trajectory planning adjusts the z-position of the drill according to the task completion level at each discrete point, and forms the 3D drilling path via constrained cubic spline interpolation while avoiding overshoot. The task completion level recognition uses a DSSD-inspired deep learning model to estimate the task completion level of each discrete point. Since an egg has similar characteristics to a mouse skull in terms of shape, thickness and mechanical properties, removing the egg shell without damaging the membrane underneath was chosen as the simulation task. The proposed method was evaluated using a 6-DOF robotic arm holding a drill and achieved a success rate of 80% out of 20 trials.Comment: Accepted on IROS 2023, 8 page

SHEEP AS ANIMAL MODEL IN MINIMALLY INVASIVE NEUROSURGERY IN EDEN2020

Glioblastomas (GBMs) is a malignant type of central nervous system tumours and its presentation is almost 80% of all malignant primary brain neoplasia. This kind of tumour is highly invasive infiltrating the white matter area and is confined to the central nervous with a very poor patient outcome survival around 10 months. Of the existing treatment approaches, Convection Enhanced drug Delivery (CED) offers several advantages for the patient but still suffers from significant shortcomings. Enhanced Delivery Ecosystem for Neurosurgery in 2020 (EDEN2020) is a European project supported with a new catheter development as the key project point in an integrated technology platform for minimally invasive neurosurgery. Due to the particular anatomy and size, sheep (Ovis aries) have been selected as experimental large animal model and a new Head Frame system MRI/CT compatible has been made and validated ad hoc for the project. In order to understand experimentally the best target point for the catheter introduction a sheep brain DTI atlas has been created. Corticospinal tract (CST), corpus callosum (CC), fornix (FX), visual pathway (VP) and occipitofrontal fascicle (OF), have been identified bilaterally for all the animals. Three of these white matter tracts, the corpus callosum, the fornix and the corona radiata, have been selected to understand the drugs diffusion properties and create a computational model of diffusivity inside the white matter substance. The analysis have been conducted via Focused Ion Beam using scanning Electron Microscopy combined with focused ion beam milling and a 2D analysis and 3D reconstruction made. The results showed homogeneous myelination via detection of ~40% content of lipids in all the different fibre tracts and the fibrous organisation of the tissue described as composite material presenting elliptical tubular fibres with an average cross-sectional area of circa 0.52\u3bcm2 and an estimated mean diameter of 1.15\u3bcm. Finally, as the project is currently ongoing, we provided an overview on the future experimental steps focalised on the brain tissue damage after the rigid catheter introduction

Developing preclinical devices for neuroscience research in the fields of animal tracking, fMRI acquisition, and 3D histology cutting

[ES] La neurociencia es un campo que abarca muchas especialidades. El objetivo de esta tesis es subsanar algunas carencias tecnológicas que existen en los métodos actuales de experimentación animal en neurociencia. En esta tesis, se presentan seis proyectos, que tendrán como objetivo mejorar el "Principio de las tres R", el cual fue enunciado por los biólogos ingleses W. M. S. Russell y R. L. Burch, durante la experimentación animal. El comportamiento es uno de los aspectos más importantes de la vida animal. Depende de los vínculos entre los animales, sus sistemas nerviosos y sus entornos. Para estudiar el comportamiento de los animales de laboratorio, se necesitan varias herramientas, pero una herramienta de seguimiento es esencial para llevar a cabo un estudio de comportamiento exhaustivo. Varias herramientas de seguimiento visual están actualmente disponibles. Sin embargo, todas tienen algunos inconvenientes. Por ejemplo, en una situación en la que un animal está dentro de una madriguera o cerca de otros animales, las cámaras de rastreo (tracking) no siempre pueden detectar la ubicación precisa o el movimiento del animal. Por esta razón, los entornos enriquecidos para intentar recrear el hábitat natural de los animales en experimentación no pueden utilizarse, ya que los datos recopilados son insuficientes/inexactos. Con la finalidad de mejorar los experimentos de tracking RFID Assisted Tracking Tile (RATT) es presentado en esta tesis. RATT es un sistema de seguimiento basado en tecnología de identificación pasiva de radiofrecuencia (RFID) y está compuesto por baldosas electrónicas con las que se puede construir una gran superficie, sobre la cual los animales pueden moverse libremente. Esto permite la identificación más precisa de los animales, así como el seguimiento de sus movimientos. Este sistema, que también se puede combinar con un sistema de seguimiento con cámaras, allana el camino para estudios completos de comportamiento en entornos enriquecidos. Dada la capacidad de rastrear animales y, por lo tanto, realizar experimentos de comportamiento exhaustivos, es posible observar cómo se comportan los sujetos desde un punto de vista externo. Sin embargo, si queremos comprender lo que sucede en el cerebro de estos sujetos, es necesario aplicar otras técnicas de análisis, por ejemplo, el estudio de señales dependientes del nivel de oxígeno en la sangre (BOLD, por sus siglas en inglés). Las señales BOLD se basan en las respuestas vasculares a la activación neuronal y se utilizan ampliamente en estudios de investigación clínicos y preclínicos. En entornos preclínicos, los animales suelen ser anestesiados. Sin embargo, los anestésicos causan cambios en la fisiología de los animales, p. Ej. hipotermia, y esto tiene el potencial de alterar las señales funcionales de MRI (fMRI). Para evitar la hipotermia en roedores anestesiados, se presenta TherMouseDuino. Este es un sistema de control automático de temperatura de código abierto, que reduce las fluctuaciones de la temperatura, lo que proporciona condiciones sólidas para realizar experimentos de resonancia magnética funcional. En los cursos de biología y neurociencia, la anatomía del cerebro se enseña generalmente utilizando imágenes de resonancia magnética (IRM) o secciones histológicas de diferentes planos. Estos muestran las áreas macroscópicas más importantes en el cerebro de un animal. Sin embargo, este método no es dinámico ni intuitivo. En esta tesis se presenta un cerebro de rata impreso en 3D con fines educativos. La manipulación manual de la estructura, facilitada por la ampliación de sus dimensiones, junto con la capacidad de desmontar el "cerebro" en algunas de sus partes principales, facilita la comprensión de la organización 3D del sistema nervioso. Este es un método alternativo y mejorado para enseñar a los estudiantes en general y a los biólogos, en particular, la anatomía del cerebro de rata.[CA] La neurociència és un camp que abasta moltes especialitats. L'objectiu d'aquesta tesi és esmenar algunes manques tecnològiques que existeixen en els mètodes actuals d'experimentació animal en neurociència. En aquesta tesi, es presenten sis projectes, que tindran com a objectiu millorar el "Principi de les tres R", el qual va ser enunciat pels biòlegs anglesos W. M. S. Russell i R. L. Burch, durant l'experimentació animal. El comportament és un dels aspectes m'és importants de la vida animal. Depèn dels vincles entre els animals, els seus sistemes nerviosos i els seus entorns. Per estudiar el comportament dels animals de laboratori, es necessiten diverses eines, però` una eina de seguiment és essencial per a dur a terme un estudi de comportament exhaustiu. Diverses eines de seguiment visual estan actualment disponibles. No obstant això, totes tenen alguns inconvenients. Per exemple, en una situació en la qual un animal esta` dins d'un cau o prop d'altres animals, les cambres de rastreig (tracking) no sempre poden detectar la ubicació precisa o el moviment de l'animal. Per aquesta raó, els entorns enriquits per a intentar recrear l'hàbitat natural dels animals en experimentació no poden utilitzar-se, ja que les dades recopilades són insuficients/inexactes. Amb la finalitat de millorar els experiments de tracking/seguiment RFID Assisted Tracking Tile (RATT) és presentat en aquesta tesi. RATT es un sistema de seguiment basat en tecnologia d'identificació passiva de radiofreqüència (RFID) i esta` compost per rajoles electròniques amb les quals es pot construir una gran superfície, sobre la qual els animals poden moures lliurement. Això permet la identificació més precisa dels animals, així com el seguiment dels seus moviments. Aquest sistema, que també es pot combinar amb un sistema de seguiment amb cambres, aplana el camí per a estudis complets de comportament en entorns enriquits. Donada la capacitat de rastrejar animals i, per tant, realitzar experiments de comportament exhaustius, és possible observar com es comporten els subjectes des d'un punt de vista extern. No obstant això, si volem comprendre el que succeeix en el cervell d'aquests subjectes, és necessari aplicar altres tècniques d'anàlisis, per exemple, l'estudi de senyals dependents del nivell d'oxigen en la sang (BOLD, per les seues sigles en anglès). Els senyals BOLD es basen en les respostes vasculars a l'activació neuronal i s'utilitzen àmpliament en estudis d'investigació clínics i preclínics. En entorns preclínics, els animals solen ser anestesiats. No obstant això, els anestèsics causen canvis en la fisiologia de els animals, per exemple hipotèrmia, i això te el potencial d'alterar els senyals funcionals de MRI (fMRI). Per a evitar la hipotèrmia en rosegadors anestesiats, es presenta TherMouseDuino. Aquest és un sistema de control automàtic de temperatura de codi obert, que redueix les fluctuacions de la temperatura, la qual cosa proporciona condicions solides per a realitzar experiments de ressonància magnètica funcional. En els cursos de biologia i neurociència, l'anatomia del cervell s'ensenya generalment utilitzant imatges de ressonància magnètica (IRM) o seccions histològiques de diferents plans. Aquests mostren les àrees macroscòpiques més importants en el cervell de un animal. No obstant això, aquest mètode no és dinàmic ni intuïtiu. En aquesta tesi es presenta un cervell de rata imprès en 3D amb finalitats educatius. La manipulació manual de l'estructura, facilitada per l'ampliació de les seues dimensions, juntament amb la capacitat de desmuntar el "cervell" en algunes de les seues parts principals, facilita la comprensió de l'organització 3D del sistema nerviós. Aquest és un mètode alternatiu i millorat per a ensenyar a els estudiants en general i als biòlegs, en particular, l'anatomia del cervell de rata.[EN] Neuroscience is a field that covers many specialties. The objective of this thesis is to correct some technological deficiencies that exist in current methods of animal experimentation in neuroscience. In this thesis, six projects are presented, which will aim to improve the "Principle of the three Rs" in animal experimentation enunciated by the English biologists W. M. S. Russell and R. L. Burch. In the present era of impressive progress in neuroscience, it is still not arguable that a complete understanding of the brain cannot be possible without a comparable understanding of animal behavior. In order to study the behavior of laboratory animals, various tools are needed, being a reliable tracking system one of the most important to follow large populations of individual subjects that interact in complex manners. Several visual tracking tools are currently available. However, they all have some drawbacks. For example, in a situation where an animal is inside a cave, or is in close proximity to other animals, tracking cameras cannot always detect the precise location or movement of the animal. For this reason, environments that have been enriched in order to attempt to recreate the natural habitat of the animals under experiment, cannot be used, as the data gathered is insufficient/inaccurate. In order to improve the current tracking systems , the RATT is presented. RATT is a tracking system based on passive RFID technology and it is composed of electronic tiles. Using several tiles, a large surface area, on which the animals can move freely, can be built. This enables the more accurate identification of the animals, as well as the tracking of their movements. This system, which can also be combined with a visual tracking system, paves the way for complete behavioral studies in enriched environments. Given the ability to track animals and thus conduct thorough behavioral experiments, it is possible to observe how the subjects behave from an external viewpoint. However, if we want to understand what is going on in the brains of these subjects, it is necessary to apply other analysis techniques, for example the study of BOLD signals. BOLD signals are based on vascular responses to neuronal activation and are used extensively in clinical and preclinical research studies. In preclinical settings, animals are usually anesthetized. However, anesthetics cause changes in the physiology of the animals, e.g. hypothermia, and this has the potential to disrupt fMRI signals. In order to avoid hypothermia in anesthetized rodents, TherMouseDuino is presented. This is an Open-Source automatic temperature control system, which reduces temperature fluctuations, thus providing robust conditions in which to perform fMRI experiments. In biology and neuroscience courses, brain anatomy is generally taught using MRI or histological sections of different planes. These show the most important macroscopic areas in an animals' brain. However, this method is neither dynamic nor intuitive. An anatomical 3D printed rat brain with educative purposes is presented in this thesis. Hand manipulation of the structure, facilitated by the scaling up of its dimensions, together with the ability to dismantle the "brain" into some of main its constituent parts, facilitates the understanding of the 3D organization of the nervous system. This is an alternative and improved method for teaching students in general and biologists, in particular, the rat brain anatomy.This work was supported in part by the Spanish Ministerio de Economía y Competitividad (MINECO) and FEDER funds under grants BFU2015-64380-C2-2-R (D.M.) and BFU2015-64380-C2-1-R, by EU Horizon 2020 Program 668863-SyBil-AA grant (S.C.). S.C. acknowledges financial support from the Spanish State Research Agency, through the “Severo Ochoa” Programme for Centres of Excellence in R&D (ref. SEV-2013-0317) and by a grant “Ayudas para la formación de personal investigador (FPI)” from the Vicerrectorado de Investigación, Innovación y Transferencia of the Universitat Politècnica de València.Quiñones Colomer, DR. (2019). Developing preclinical devices for neuroscience research in the fields of animal tracking, fMRI acquisition, and 3D histology cutting [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/118795TESI

Intraoperative Navigation Systems for Image-Guided Surgery

Recent technological advancements in medical imaging equipment have resulted in a dramatic improvement of image accuracy, now capable of providing useful information previously not available to clinicians. In the surgical context, intraoperative imaging provides a crucial value for the success of the operation. Many nontrivial scientific and technical problems need to be addressed in order to efficiently exploit the different information sources nowadays available in advanced operating rooms. In particular, it is necessary to provide: (i) accurate tracking of surgical instruments, (ii) real-time matching of images from different modalities, and (iii) reliable guidance toward the surgical target. Satisfying all of these requisites is needed to realize effective intraoperative navigation systems for image-guided surgery. Various solutions have been proposed and successfully tested in the field of image navigation systems in the last ten years; nevertheless several problems still arise in most of the applications regarding precision, usability and capabilities of the existing systems. Identifying and solving these issues represents an urgent scientific challenge. This thesis investigates the current state of the art in the field of intraoperative navigation systems, focusing in particular on the challenges related to efficient and effective usage of ultrasound imaging during surgery. The main contribution of this thesis to the state of the art are related to: Techniques for automatic motion compensation and therapy monitoring applied to a novel ultrasound-guided surgical robotic platform in the context of abdominal tumor thermoablation. Novel image-fusion based navigation systems for ultrasound-guided neurosurgery in the context of brain tumor resection, highlighting their applicability as off-line surgical training instruments. The proposed systems, which were designed and developed in the framework of two international research projects, have been tested in real or simulated surgical scenarios, showing promising results toward their application in clinical practice

Development of a New Tool for 3D Modeling for Regenerative Medicine

The effectiveness of therapeutic treatment based on regenerative medicine for degenerative diseases (i.e., neurodegenerative or cardiac diseases) requires tools allowing the visualization and analysis of the three-dimensional (3D) distribution of target drugs within the tissue. Here, we present a new computational procedure able to overcome the limitations of visual analysis emerging by the examination of a molecular signal within images of serial tissue/organ sections by using the conventional techniques. Together with the 3D anatomical reconstitution of the tissue/organ, our framework allows the detection of signals of different origins (e.g., marked generic molecules, colorimetric, or fluorimetric substrates for enzymes; microRNA; recombinant protein). Remarkably, the application does not require the employment of specific tracking reagents for the imaging analysis. We report two different representative applications: the first shows the reconstruction of a 3D model of mouse brain with the analysis of the distribution of the β-Galactosidase, the second shows the reconstruction of a 3D mouse heart with the measurement of the cardiac volume

Brain response to a humanoid robot in areas implicated in the perception of human emotional gestures

BACKGROUND: The humanoid robot WE4-RII was designed to express human emotions in order to improve human-robot interaction. We can read the emotions depicted in its gestures, yet might utilize different neural processes than those used for reading the emotions in human agents. METHODOLOGY: Here, fMRI was used to assess how brain areas activated by the perception of human basic emotions (facial expression of Anger, Joy, Disgust) and silent speech respond to a humanoid robot impersonating the same emotions, while participants were instructed to attend either to the emotion or to the motion depicted. PRINCIPAL FINDINGS: Increased responses to robot compared to human stimuli in the occipital and posterior temporal cortices suggest additional visual processing when perceiving a mechanical anthropomorphic agent. In contrast, activity in cortical areas endowed with mirror properties, like left Broca’s area for the perception of speech, and in the processing of emotions like the left anterior insula for the perception of disgust and the orbitofrontal cortex for the perception of anger, is reduced for robot stimuli, suggesting lesser resonance with the mechanical agent. Finally, instructions to explicitly attend to the emotion significantly increased response to robot, but not human facial expressions in the anterior part of the left inferior frontal gyrus, a neural marker of motor resonance. CONCLUSIONS: Motor resonance towards a humanoid robot, but not a human, display of facial emotion is increased when attention is directed towards judging emotions. SIGNIFICANCE: Artificial agents can be used to assess how factors like anthropomorphism affect neural response to the perception of human actions

ISMCR 1994: Topical Workshop on Virtual Reality. Proceedings of the Fourth International Symposium on Measurement and Control in Robotics

This symposium on measurement and control in robotics included sessions on: (1) rendering, including tactile perception and applied virtual reality; (2) applications in simulated medical procedures and telerobotics; (3) tracking sensors in a virtual environment; (4) displays for virtual reality applications; (5) sensory feedback including a virtual environment application with partial gravity simulation; and (6) applications in education, entertainment, technical writing, and animation

The Cape Town Stereotactic pointer clinical development and Applications

This dissertation describes the development and clinical use of a novel stereotactic neurosurgical system, the Cape Town Stereotactic Pointer (CTSP). This system has four main components; a halo containing three fiducials also serves as the platform for a tripod pointing device which is set with the aid of a 3D phantom or a printed setting diagram, and software which enables transformation of imaging space into patient space. Laboratory tests indicated an application accuracy of 1.9 +/- 0.6mm using the 3D phantom to set the tripod. From the first clinical application, the system underwent a series of iterations which could broadly be divided into four successive phases of refinement. This took place over a six year period, encompassing one hundred patients who underwent 115 stereotactic procedures. Indications for surgery included biopsy (62.6%), aspiration (15.7%) and cannulation (21.7%) and the surgical objective was realized in 101/109 cases (92.7%). Given the fact that six of the eight failures represented errors of surgical judgment that could not be ascribed to the device, and each of two system errors resulted in a significant modification to the system, the CTSP demonstrated a satisfactory level of accuracy in the clinical setting. This was accomplished at an acceptable complication rate, with one death five days after surgery attributable to a stereotactic procedure (mortality 0.9%) and major morbidity in two cases (1.7%); thirteen patients experienced minor complications, all of which proved to be transient (11.3%). A simple protocol for use of the CTSP evolved over the course of this study, making it easier for neurosurgeons from varying backgrounds to introduce stereotaxis into their practice with the help of this system. In addition to satisfactory levels of clinical reliability and safety, the system was versatile and also well tolerated by patients. It is hoped that the CTSP provides a costeffective alternative for neurosurgeons working in under-resourced settings. Sixty units of the production version of the CTSP have been sold and the system is now in use in ten countries

Patient Specific Systems for Computer Assisted Robotic Surgery Simulation, Planning, and Navigation

The evolving scenario of surgery: starting from modern surgery, to the birth of medical imaging and the introduction of minimally invasive techniques, has seen in these last years the advent of surgical robotics. These systems, making possible to get through the difficulties of endoscopic surgery, allow an improved surgical performance and a better quality of the intervention. Information technology contributed to this evolution since the beginning of the digital revolution: providing innovative medical imaging devices and computer assisted surgical systems. Afterwards, the progresses in computer graphics brought innovative visualization modalities for medical datasets, and later the birth virtual reality has paved the way for virtual surgery. Although many surgical simulators already exist, there are no patient specific solutions. This thesis presents the development of patient specific software systems for preoperative planning, simulation and intraoperative assistance, designed for robotic surgery: in particular for bimanual robots that are becoming the future of single port interventions. The first software application is a virtual reality simulator for this kind of surgical robots. The system has been designed to validate the initial port placement and the operative workspace for the potential application of this surgical device. Given a bimanual robot with its own geometry and kinematics, and a patient specific 3D virtual anatomy, the surgical simulator allows the surgeon to choose the optimal positioning of the robot and the access port in the abdominal wall. Additionally, it makes possible to evaluate in a virtual environment if a dexterous movability of the robot is achievable, avoiding unwanted collisions with the surrounding anatomy to prevent potential damages in the real surgical procedure. Even if the software has been designed for a specific bimanual surgical robot, it supports any open kinematic chain structure: as far as it can be described in our custom format. The robot capabilities to accomplish specific tasks can be virtually tested using the deformable models: interacting directly with the target virtual organs, trying to avoid unwanted collisions with the surrounding anatomy not involved in the intervention. Moreover, the surgical simulator has been enhanced with algorithms and data structures to integrate biomechanical parameters into virtual deformable models (based on mass-spring-damper network) of target solid organs, in order to properly reproduce the physical behaviour of the patient anatomy during the interactions. The main biomechanical parameters (Young's modulus and density) have been integrated, allowing the automatic tuning of some model network elements, such as: the node mass and the spring stiffness. The spring damping coefficient has been modeled using the Rayleigh approach. Furthermore, the developed method automatically detect the external layer, allowing the usage of both the surface and internal Young's moduli, in order to model the main parts of dense organs: the stroma and the parenchyma. Finally the model can be manually tuned to represent lesion with specific biomechanical properties. Additionally, some software modules of the simulator have been properly extended to be integrated in a patient specific computer guidance system for intraoperative navigation and assistance in robotic single port interventions. This application provides guidance functionalities working in three different modalities: passive as a surgical navigator, assistive as a guide for the single port placement and active as a tutor preventing unwanted collision during the intervention. The simulation system has beed tested by five surgeons: simulating the robot access port placemen, and evaluating the robot movability and workspace inside the patient abdomen. The tested functionalities, rated by expert surgeons, have shown good quality and performance of the simulation. Moreover, the integration of biomechanical parameters into deformable models has beed tested with various material samples. The results have shown a good visual realism ensuring the performance required by an interactive simulation. Finally, the intraoperative navigator has been tested performing a cholecystectomy on a synthetic patient mannequin, in order to evaluate: the intraoperative navigation accuracy, the network communications latency and the overall usability of the system. The tests performed demonstrated the effectiveness and the usability of the software systems developed: encouraging the introduction of the proposed solution in the clinical practice, and the implementation of further improvements. Surgical robotics will be enhanced by an advanced integration of medical images into software systems: allowing the detailed planning of surgical interventions by means of virtual surgery simulation based on patient specific biomechanical parameters. Furthermore, the advanced functionalities offered by these systems, enable surgical robots to improve the intraoperative surgical assistance: benefitting of the knowledge of the virtual patient anatomy

An Electrophysiological Study Of Voluntary Movement and Spinal Cord Injury

Voluntary movement is generated from the interaction between neurons in our brain and the neurons in our spinal cord that engage our muscles. A spinal cord injury destroys the connection between these two regions, but parts of their underlying neural circuits survive. A new class of treatment (the brain-machine interface) takes advantage of this fact by either a) recording neural activity from the brain and predicting the intended movement (neural prosthetics) or b) stimulating neural activity in the spinal cord to facilitate muscle activity (spinal stimulation). This thesis covers new research studying the brain-machine interface and its application for spinal injury. First, the electrical properties of the microelectrode (the main tool of the brain-machine interface) are studied during deep brain recording and stimulation. This work shows that the insulation coating the electrode forms a capacitor with the surrounding neural tissue. This capacitance causes large spikes of voltage in the surrounding tissue during deep brain stimulation, which will cause electrical artifacts in neural recordings and may damage the surrounding neurons. This work also shows that a coaxially shielded electrode will block this effect. Second, the activity of neurons in the parietal cortex is studied during hand movements, which has applications for neural prosthetics. Prior work suggests that the parietal cortex encodes a state-estimator [1], which combines sensory feedback with the internal efference copy to predict the state of the hand. To test this idea, we used a visual lag to misalign sensory feedback from the efference copy. The expectation was that a state-estimator would unknowingly combine the delayed visual feedback with the current efference information, resulting in incorrect predictions of the hand. Our results show a drop in correlation between neural activity in the parietal cortex and hand movement during a visual lag, supporting the idea that the parietal cortex encodes a state-estimator. This correlation gradually recovers over time, showing that parietal cortex is adaptive to sensory delays. Third, while the intention of spinal stimulation was to interact locally with neural circuits in the spinal cord, results from the clinic show that electrical stimulation of the lumbosacral enlargement enables paraplegic patients to regain voluntary movement of their legs [2]. This means that spinal stimulation facilitates communication across an injury site. To further study this effect, we developed a new behavioral task in the rodent. Rats were trained to kick their right hindlimb in response to an auditory cue. The animals then received a spinal injury that caused paraplegia. After injury, the animals recovered the behavior (they could kick in response to the cue), but only during spinal stimulation. Their recovered behavior was slower and more stereotyped than their pre-injury response. Administering quipazine to these rodents disrupted their ability to respond to the cue, suggesting that serotonin plays an important role in the recovered pathway. This work proves that the new behavioral task is a successful tool for studying the recovery of voluntary movement. Future work will combine cortical recordings with this behavioral task in the rodent to study plasticity in the nervous system and improve treatment of spinal cord injuries. [1] Mulliken, Grant H., Sam Musallam, and Richard A. Andersen. "Forward estimation of movement state in posterior parietal cortex." Proceedings of the National Academy of Sciences105.24 (2008): 8170-8177. [2] Harkema, Susan, et al. "Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study." The Lancet 377.9781 (2011): 1938-1947.</p