Dr. Antoniades was supported by the National Institute of Health Research (NIHR) and by the Dementias and Neurodegenerative Diseases Research Network (DENDRON) and by the Wellcome Trust. Dr FitzGerald was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre.

El comité de ética local aprobó el estudio y conocimiento de causa su consentimiento se obtuvo de los participantes como se detalla a continuación en el apartado 1. 1. El consentimiento del participante <ol><li> Proporcionar a los participantes una hoja de información que explica en detalle lo que la sesión de pruebas incluirá. </li><li> Después de que los participantes tienen la oportunidad de leer y discutir cualquier pregunta, duda u otros asuntos relacionados a su participación en el estudio, ir a través del formulario de consentimiento con ellos, explicando cada punto en el formulario de consentimiento y darles la oportunidad de formular las preguntas que pudieran tener. Pídale al participante que complete el formulario. </li></ol> 2. Configuración de la Saccadometer <ol><li> Coloque el dispositivo sobre la cabeza del paciente, asegurado por una correa elástica ajustable y que descansa sobre el puente de la nariz. Debido a que los estímulos se mueven exactamente con la cabeza, no reposacabezas es necesario y el dispositivo es cómodo de WEAr. </li><li> Pedir al paciente que se siente en el 1,5 m de una pantalla plana mate. </li><li> Asegúrese de que la iluminación ambiental es tenue, así que los estímulos (puntos de luz roja) se ven claramente. </li></ol> 3. Grabación de una sesión sacádica Nota: A modo de ejemplo, se describe aquí un protocolo estándar que pone a prueba tanto prosaccades y antisaccades 8. Este protocolo consiste en cinco bloques: 60, 40 prosaccades antisaccades x 3, y 60 prosaccades con un descanso de 1 minuto entre bloques. La sesión dura unos 40 minutos. <ol><li> Configurar el saccadometer de modo que para cada ensayo se muestra el objetivo central de la fijación de un periodo aleatorio delantera de 1,0 - 2,0 segundos, después de lo cual se extingue y aparece uno de los objetivos periféricos, al azar a la derecha o izquierda 9. Nota: Los tres objetivos son puntos de luz roja proyectada sobre la pantalla delante del participante (véase el punto 2.2) por los láseres de baja potencia integrado en el saccadometer. El aut saccadometerinterruptores omatically los láseres de encendido y apagado para la pantalla / apagar las metas en la secuencia necesaria. </li><li> Instruir al participante que la prueba consta de cinco bloques con un descanso de un minuto entre bloques. </li><li> Antes del primer bloque de instruir al participante para mover sus ojos tan rápida y precisa como sea posible para seguir el punto rojo que salta del centro hacia un lado o el otro y darles instrucciones para hacer esto 60 veces. </li><li> Ajuste el saccadometer para generar una secuencia de 60 ensayos. Pulse el botón en el saccadometer para iniciar el primer bloque de ensayos (prosaccades). </li><li> Después de la terminación del primer bloque, deje un espacio un minuto antes del segundo bloque. Restablecer el saccadometer para generar una secuencia de 40 ensayos, y hacia el final de la brecha minuto, instruir al participante para el siguiente bloque de mover los ojos tan pronto como sea posible en la dirección opuesta al punto rojo, y explicar que lo harán ser requeridos para hacer esto 40 veces. Iniciar el secEn segundo bloque de ensayos (antisaccades). </li><li> Después de la terminación del segundo bloque, dejar un mayor espacio de 1 min, repita la instrucción en el paso 3.5 e iniciar el tercer bloque de ensayos (antisaccades). </li><li> Después de la terminación de la tercera bloque, dejar un mayor espacio de 1 min, repita la instrucción en el paso 3.5 e iniciar el cuarto bloque de ensayos (antisaccades). </li><li> Una vez completada la cuarta bloque, dejar un mayor espacio de 1 min, y explicar que para el bloque final de las pruebas a los participantes que mover sus ojos tan rápida y precisa como sea posible para seguir el punto rojo que salta del centro hacia un lado o el otra, exactamente como lo hicieron en el primer bloque. </li><li> Restablecer el saccadometer para generar una secuencia de 60 ensayos, e iniciar el bloque final de los ensayos (prosaccades). </li></ol><img alt="Figura 2" src="/files/ftp_upload/53640/53640fig2.jpg" /> Figura 2. Tareas movimiento del ojo. Illustrati esquemáticosen la que muestra dos ejemplos de tareas sacádicos. La mancha de color azul representa el blanco y el círculo azul de puntos representa la zona de fijación. IZQUIERDA muestra una tarea prosaccadic donde está el tema impulsó a buscar hacia el objetivo. Derecha muestra una antisacádica en la que se pide al sujeto que apartar la mirada del estímulo visual . Esto requiere la inhibición de la respuesta prosaccade más natural y generación de una sacada en la dirección opuesta. <a href="https://www.jove.com/files/ftp_upload/53640/53640fig2large.jpg" target="_blank">Por favor, haga clic aquí para ver una versión más grande de esta figura.</a> 4. Configuración del estimulador cerebral profunda Nota: Para los participantes con estimuladores cerebrales profundos realizar las pruebas hasta ahora con el sistema estimulador se ejecuta como normal, es decir, un conjunto de datos &#39;en la estimulación&#39; se ha obtenido. Las pruebas ahora debe repetirse con el sistema estimulador apagado (para el control de los participantes sanos sin sistemas DBS no se aplicará esta sección). <ol><li> Cambiar el sistema DBS fuera. Para ello, un personal clínico entrenado. Permitir 30 minutos antes de la prueba. </li><li> Repita la prueba sacádicos (pasos 3.2 a 3.9) para obtener un conjunto completo de datos &quot;fuera de estimulación&quot;. </li><li> Cambiar el sistema DBS de nuevo (de nuevo este debe ser realizado por personal clínico entrenado adecuadamente). </li></ol> Análisis 5. Datos Nota: Para los participantes con estimuladores cerebrales profundos realizar las pruebas hasta ahora con el sistema estimulador se ejecuta como normal, es decir, un conjunto de datos &#39;en la estimulación&#39; se ha obtenido. Las pruebas ahora debe repetirse con el sistema estimulador apagado (para los participantes de control sanos y sin sistemas DBS esta sección no se aplicarán). <ol><li> Descargar los datos en bruto de la saccadometer a un ordenador para su análisis. </li><li> Utilice el programa de software del saccadometer para excluir movimientos sacádicos distorsiónTed por parpadeos y movimientos de la cabeza, y las variables para calcular incluyendo latencias sacádicos, velocidades máximas, y amplitudes. Nota: Los registros contaminados por los movimientos de la cabeza excesivas o parpadea se eliminan automáticamente por el software. <ol><li> Retire las sacadas con una latencia inferior a 80 ms o superior a 1.000 ms. Nota: la latencia sacádico se calcula automáticamente utilizando un algoritmo de detección de movimiento sacádico basado en la velocidad y la aceleración. El inicio de una sacada se identifica como el punto en que la velocidad del ojo es superior a un umbral de 5 grados / seg. </li></ol></li></ol>

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The authors have nothing to disclose.

El factor más crítico en la obtención de datos sacádicos buena calidad es asegurar que las instrucciones dadas al participante son claras y precisas. Por ejemplo, si las instrucciones para la tarea antisaccadic no están del todo claras, el participante es probable que ejecute prosaccades lugar. Las grabaciones también pueden estar en mal estado si el participante no puede ver claramente los estímulos o la saccadometer no puede medir con precisión la posición del ojo. Así, si los datos parecen ser de baja calid...

En los últimos años ha habido un creciente interés en el uso de las mediciones de los tiempos de reacción como una forma cuantitativa y no invasiva de obtención de información acerca de los mecanismos de alto nivel de toma de decisión 1 neural. Un tipo de tiempo de reacción que se ha estudiado ampliamente es el tiempo necesario para iniciar una sacada en la presentación de un estímulo visual, conocido como latencia sacádico. Las sacadas son los movimientos oculares rápidos que se producen cuando nos desplazamos rápidamente la mirada de un lugar a otro. Ellos son el tipo más común de los movimientos oculares que hacemos, que se producen con una frecuencia de por lo general dos o tres por segundo. Cada movimiento sacádico es en efecto una decisión de mirar a una cue en el mundo visual en lugar de otro 2. Los caminos de los nervios que controlan los movimientos oculares se han estudiado ampliamente y están bastante bien documentado 3. El uso de equipo electrónico sensible, aspectos de la función oculomotora pueden ser precisa y objectively cuantificado. Esto facilita el estudio detallado de los propios movimientos de los ojos, pero también les permite ser usados ​​como una herramienta para investigar otras áreas de la neurofisiología y la fisiopatología. Ojo medición de movimiento puede proporcionar información útil sobre los estados de enfermedad. Los movimientos oculares sacádicos han recientemente, por ejemplo, recibió tanta atención como posibles marcadores biológicos en los trastornos neurodegenerativos, incluyendo las enfermedades de Huntington y Parkinson 4,5 6,7, y es bien establecido que los tiempos de reacción sacádicos tienden a ser más lenta de lo normal en estas condiciones. Los usos potenciales de medición sacádicos incluyen ayudas para el diagnóstico y seguimiento de la enfermedad. tareas sacádicos van desde la prosaccade sencilla (mirando lo más rápidamente posible hacia un estímulo visual que aparece de repente a la izquierda o la derecha) para tareas más complejas tales como la antisacádica (mirando lo más rápido posible hacia el lado opuesto a un estímulo visual) o memoria- sacada guiada (mirandohacia el lugar acordado de un objetivo que ya no está allí). La estimulación cerebral profunda es un tratamiento eficaz para varias condiciones neurológicas. Se utiliza más comúnmente para tratar los síntomas motores de la enfermedad de Parkinson incluyendo temblor, rigidez, bradicinesia, y discinesia. También se utiliza para otros trastornos del movimiento incluyendo distonía y el temblor esencial, y con menos frecuencia para el dolor neuropático, epilepsia, y condiciones psiquiátricas como el trastorno obsesivo compulsivo. Es el único escenario en el que los científicos tienen acceso eléctrico directo a las estructuras profundas del cerebro humano in vivo y por lo tanto ofrece una valiosa oportunidad para la neurología experimental. Una variedad de objetivos son estimulados dependiendo de la afección a tratar, incluyendo varios lugares en los ganglios basales, muchos de los cuales están implicados en las vías oculomotores. Esto significa que una amplia gama de estudios puede llevarse a cabo utilizando el sistema de DBS para entregar estimulacióna una ubicación cerebro dado y un dispositivo de seguimiento de los ojos para registrar y analizar sus efectos. Dependiendo del paradigma experimental, estos estudios pueden proporcionar información acerca de la fisiología de la región que está siendo estimulado, los efectos de la enfermedad, o el mecanismo por el cual DBS está trabajando en ese entorno particular. En este artículo se describe un enfoque general de la prueba de movimiento ocular sacádico en pacientes de estimulación cerebral profunda. Existen varios tipos diferentes de equipos de seguimiento de los ojos están disponibles. Para la investigación descrita en este protocolo se utilizó un saccadometer portátil para registrar los movimientos oculares sacádicos horizontales. Saccadometers portátiles tienen la ventaja de no requerir apoyacabezas (véase la Figura 1), lo que significa que las sesiones son más cómodos para los pacientes con enfermedad de Parkinson, especialmente para aquellos que sufren de discinesias severas. El saccadometer usada aquí es ligero y aproximadamente 5 cm de ancho y 10 cm de altura. El measu saccadometermovimientos oculares cosa por el uso de oculografía infrarroja directa: una fuente de infrarrojos y un sensor colocado en frente de la luz medial uso canto reflejada desde la córnea para establecer la posición de rotación del globo ocular en intervalos de milisegundos. Con el fin de adquirir datos de buena calidad para el análisis de la saccadometer debe muestra a una velocidad de al menos 1 kHz con al menos una resolución de 12 bits. En el saccadometer utilizado aquí los estímulos visuales fueron tres de color rojo 13 cd m-2 puntos de luz producida por el láser construida en baja potencia, cada punto que subtiende unos 0,1 grados, con un punto en la línea media y los otros dos a ± 10 grados (es decir, , a la derecha ya la izquierda). <img alt="Figura 1" src="/files/ftp_upload/53640/53640fig1.jpg" /> Figura 1. El Saccadometer. Cabeza montada saccadometer unido a una banda elástica y descansando sobre el puente de la nariz. Cuatro láseres en miniatura proyectan objetivo visuals sobre una superficie mate, y movimientos de los ojos de los participantes se miden por los transductores de reflectancia de infrarrojos diferenciales en el lado nasal de cada ojo. Como los objetivos de láser se mueven con la cabeza, no son necesarios los reposacabezas. <a href="https://www.jove.com/files/ftp_upload/53640/53640fig1large.jpg" target="_blank">Haga clic aquí para ver una versión más grande de esta figura.</a>

<table border="0" cellpadding="0" cellspacing="0" width="88">
	<tbody>
		<tr>
			<td>Saccadometer device ( Ober Consulting Poland)</td>
		</tr>
		<tr>
			<td>Computer with Windows environment</td>
		</tr>
		<tr>
			<td>Software, Latency Meter for downloading the raw data from the saccadometer.</td>
		</tr>
	</tbody>
</table>

using saccadometry with deep brain stimulation to study normal and pathological brain function

The oculomotor system involves a large number of brain areas including parts of the basal ganglia, and various neurodegenerative diseases including Parkinson's and Huntington's can disrupt it. People with Parkinson's disease, for example, tend to have increased saccadic latencies. Consequently, the quantitative measurement of saccadic eye movements has received considerable attention as a potential biomarker for neurodegenerative conditions. A lot more can be learned about the brain in both health and disease by observing what happens to eye movements when the function of specific brain areas is perturbed. Deep brain stimulation is a surgical intervention used for the management of a range of neurological conditions including Parkinson's disease, in which stimulating electrodes are placed in specific brain areas including several sites in the basal ganglia. Eye movement measurements can then be made with the stimulator systems both off and on and the results compared. With suitable experimental design, this approach can be used to study the pathophysiology of the disease being treated, the mechanism by which DBS exerts it beneficial effects, and even aspects of normal neurophysiology.

La figura 3 muestra un ejemplo de sacádicos trayectorias de movimiento del ojo, a partir de paciente de la enfermedad de Parkinson con un sistema de DBS núcleo subtalámico implantado. Los dos gráficos de trazado de prosaccades del paciente con el sistema estimulador apagado (gráfico superior) y encendido (gráfico inferior). Cada traza en los gráficos muestra la trayectoria de un solo sacada, es decir, cómo la posición del ojo en grados lejos de la líne...

Watch this Scientific Journal Video about Using Saccadometry with Deep Brain Stimulation to Study Normal and Pathological Brain Function at JoVE.com

Using Saccadometry with Deep Brain Stimulation to Study Normal and Pathological Brain Function

This paper describes the use of quantitative measurement of eye movements in conjunction with stimulation of focal areas of the deep brain in order to study physiology, pathophysiology, and the mechanisms of deep brain stimulation.

Usando Saccadometry con estimulación cerebral profunda para estudiar la función cerebral normal y patológica

The oculomotor system involves a large number of brain areas including parts of the basal ganglia, and various neurodegenerative diseases including ...

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7.4K vistas.  The University of Oxford. This paper describes the use of quantitative measurement of eye movements in conjunction with stimulation of focal areas of the deep brain in order to study physiology, pathophysiology, and the mechanisms of deep brain stimulation.

Video: Using Saccadometry with Deep Brain Stimulation to Study Normal and Pathological Brain Function

Intra-Operative Behavioral Tasks in Awake Humans Undergoing Deep Brain Stimulation Surgery

Deep brain stimulation (DBS) is a surgical procedure that directs chronic, high frequency electrical stimulation to specific targets in the brain through implanted electrodes. Deep brain stimulation was first implemented as a therapeutic modality by Benabid et al. in the late 1980s, when he used this technique to stimulate the ventral intermediate nucleus of the thalamus for the treatment of tremor 1. Currently, the procedure is used to treat patients who fail to respond adequately to medical management for diseases such as Parkinson's, dystonia, and essential tremor. The efficacy of this procedure for the treatment of Parkinson's disease has been demonstrated in well-powered, randomized controlled trials 2. Presently, the U.S. Food and Drug Administration has approved DBS as a treatment for patients with medically refractory essential tremor, Parkinson's disease, and dystonia. Additionally, DBS is currently being evaluated for the treatment of other psychiatric and neurological disorders, such as obsessive compulsive disorder, major depressive disorder, and epilepsy. 
DBS has not only been shown to help people by improving their quality of life, it also provides researchers with the unique opportunity to study and understand the human brain. Microelectrode recordings are routinely performed during DBS surgery in order to enhance the precision of anatomical targeting. Firing patterns of individual neurons can therefore be recorded while the subject performs a behavioral task. Early studies using these data focused on descriptive aspects, including firing and burst rates, and frequency modulation 3. More recent studies have focused on cognitive aspects of behavior in relation to neuronal activity 4,5. This article will provide a description of the intra-operative methods used to perform behavioral tasks and record neuronal data with awake patients during DBS cases. Our exposition of the process of acquiring electrophysiological data will illuminate the current scope and limitations of intra-operative human experiments.

Deep brain stimulation surgery offers a unique opportunity to examine information encoding in the awake human brain. This article will describe intra-operative methods used to perform cognitive and behavioral tasks while simultaneously acquiring physiological data such as EMG, single-unit neuronal activity and/or local field potentials.

Intra-operatoria tareas comportamiento en seres humanos sometidos a cirugía Awake Estimulación Cerebral Profunda

Deep brain stimulation (DBS) is a surgical procedure that directs chronic, high frequency electrical stimulation to specific targets in the brain through ...

Investigación

Medicina

Eye Tracking Young Children with Autism

The rise of accessible commercial eye-tracking systems has fueled a rapid increase in their use in psychological and psychiatric research. By providing a direct, detailed and objective measure of gaze behavior, eye-tracking has become a valuable tool for examining abnormal perceptual strategies in clinical populations and has been used to identify disorder-specific characteristics1, promote early identification2, and inform treatment3. In particular, investigators of autism spectrum disorders (ASD) have benefited from integrating eye-tracking into their research paradigms4-7. Eye-tracking has largely been used in these studies to reveal mechanisms underlying impaired task performance8 and abnormal brain functioning9, particularly during the processing of social information1,10-11. While older children and adults with ASD comprise the preponderance of research in this area, eye-tracking may be especially useful for studying young children with the disorder as it offers a non-invasive tool for assessing and quantifying early-emerging developmental abnormalities2,12-13. Implementing eye-tracking with young children with ASD, however, is associated with a number of unique challenges, including issues with compliant behavior resulting from specific task demands and disorder-related psychosocial considerations. In this protocol, we detail methodological considerations for optimizing research design, data acquisition and psychometric analysis while eye-tracking young children with ASD. The provided recommendations are also designed to be more broadly applicable for eye-tracking children with other developmental disabilities. By offering guidelines for best practices in these areas based upon lessons derived from our own work, we hope to help other investigators make sound research design and analysis choices while avoiding common pitfalls that can compromise data acquisition while eye-tracking young children with ASD or other developmental difficulties.

Eye tracking has long been used to study gaze patterns in typically-developing individuals, but recent technological advancements have made its use with clinical populations, including autism, more feasible. While eye-tracking young children with autism can offer insight into early symptom manifestations, it involves methodological challenges. Suggestions for best practices are provided.

Eye Tracking niños pequeños con autismo

The rise of accessible commercial eye-tracking systems has fueled a rapid increase in their use in psychological and psychiatric research. By providing a ...

Isolation of Soluble and Insoluble PrP Oligomers in the Normal Human Brain

The central event in the pathogenesis of prion diseases involves a conversion of the host-encoded cellular prion protein PrPC into its pathogenic isoform PrPSc 1. PrPC is detergent-soluble and sensitive to proteinase K (PK)-digestion, whereas PrPSc forms detergent-insoluble aggregates and is partially resistant to PK2-6. The conversion of PrPC to PrPSc is known to involve a conformational transition of &alpha;-helical to &beta;-sheet structures of the protein. However, the in vivo pathway is still poorly understood. A tentative endogenous PrPSc, intermediate PrP* or "silent prion", has yet to be identified in the uninfected brain7.
Using a combination of biophysical and biochemical approaches, we identified insoluble PrPC aggregates (designated iPrPC) from uninfected mammalian brains and cultured neuronal cells8, 9. Here, we describe detailed procedures of these methods, including ultracentrifugation in detergent buffer, sucrose step gradient sedimentation, size exclusion chromatography, iPrP enrichment by gene 5 protein (g5p) that specifically bind to structurally altered PrP forms10, and PK-treatment. The combination of these approaches isolates not only insoluble PrPSc and PrPC aggregates but also soluble PrPC oligomers from the normal human brain. Since the protocols described here have been used to isolate both PrPSc from infected brains and iPrPC from uninfected brains, they provide us with an opportunity to compare differences in physicochemical features, neurotoxicity, and infectivity between the two isoforms. Such a study will greatly improve our understanding of the infectious proteinaceous pathogens. The physiology and pathophysiology of iPrPC are unclear at present. Notably, in a newly-identified human prion disease termed variably protease-sensitive prionopathy, we found a new PrPSc that shares the immunoreactive behavior and fragmentation with iPrPC 11, 12. Moreover, we recently demonstrated that iPrPC is the main species that interacts with amyloid-&beta; protein in Alzheimer disease13. In the same study, these methods were used to isolate Abeta aggregates and oligomers in Alzheimer's disease13, suggesting their application to non-prion protein aggregates involved in other neurodegenerative disorders.

A new species of cellular prion protein (PrPC) has recently been identified in uninfected human brains using the methods described here. These methods can be used to isolate various PrP species, while some of them are also useful in isolating other misfolded protein aggregates from human brains.

Aislamiento de oligómeros de PrP soluble e insoluble en el cerebro humano normal

The central event in the pathogenesis of prion diseases involves a conversion of the host-encoded cellular prion protein PrPC into its pathogenic isoform ...

A Novel High-resolution In vivo Imaging Technique to Study the Dynamic Response of Intracranial Structures to Tumor Growth and Therapeutics

We have successfully integrated previously established Intracranial window (ICW) technology 1-4 with intravital 2-photon confocal microscopy to develop a novel platform that allows for direct long-term visualization of tissue structure changes intracranially. Imaging at a single cell resolution in a real-time fashion provides supplementary dynamic information beyond that provided by standard end-point histological analysis, which looks solely at 'snap-shot' cross sections of tissue.
Establishing this intravital imaging technique in fluorescent chimeric mice, we are able to image four fluorescent channels simultaneously. By incorporating fluorescently labeled cells, such as GFP+ bone marrow, it is possible to track the fate of these cells studying their long-term migration, integration and differentiation within tissue. Further integration of a secondary reporter cell, such as an mCherry glioma tumor line, allows for characterization of cell:cell interactions. Structural changes in the tissue microenvironment can be highlighted through the addition of intra-vital dyes and antibodies, for example CD31 tagged antibodies and Dextran molecules.
Moreover, we describe the combination of our ICW imaging model with a small animal micro-irradiator that provides stereotactic irradiation, creating a platform through which the dynamic tissue changes that occur following the administration of ionizing irradiation can be assessed.
Current limitations of our model include penetrance of the microscope, which is limited to a depth of up to 900 &mu;m from the sub cortical surface, limiting imaging to the dorsal axis of the brain. The presence of the skull bone makes the ICW a more challenging technical procedure, compared to the more established and utilized chamber models currently used to study mammary tissue and fat pads 5-7. In addition, the ICW provides many challenges when optimizing the imaging.

A Novel High-resolution In vivo Imaging Technique to Study the Dynamic Response of Intracranial Structures to Tumor Growth and Therapeutics

We describe a novel in vivo imaging technique that couples fluorescent chimeric mice with intracranial windows and high-resolution 2-photon microscopy. This imaging platform aids studies of dynamic changes in brain tissue and microvasculature, at a single-cell level, following pathological insults and is adaptable to assess intracranial drug delivery and distribution.

Una novela de alta resolución<em&gt; En vivo</em&gt; Técnica de escaneo para el Estudio de la respuesta dinámica de estructuras intracraneales al crecimiento del tumor y Terapéutica

We have successfully integrated previously established Intracranial window (ICW) technology 1-4 with intravital 2-photon confocal microscopy to develop a ...

Lesion Explorer: A Video-guided, Standardized Protocol for Accurate and Reliable MRI-derived Volumetrics in Alzheimer's Disease and Normal Elderly

Obtaining in vivo human brain tissue volumetrics from MRI is often complicated by various technical and biological issues. These challenges are exacerbated when significant brain atrophy and age-related white matter changes (e.g. Leukoaraiosis) are present. Lesion Explorer (LE) is an accurate and reliable neuroimaging pipeline specifically developed to address such issues commonly observed on MRI of Alzheimer's disease and normal elderly. The pipeline is a complex set of semi-automatic procedures which has been previously validated in a series of internal and external reliability tests1,2. However, LE's accuracy and reliability is highly dependent on properly trained manual operators to execute commands, identify distinct anatomical landmarks, and manually edit/verify various computer-generated segmentation outputs.
LE can be divided into 3 main components, each requiring a set of commands and manual operations: 1) Brain-Sizer, 2) SABRE, and 3) Lesion-Seg. Brain-Sizer's manual operations involve editing of the automatic skull-stripped total intracranial vault (TIV) extraction mask, designation of ventricular cerebrospinal fluid (vCSF), and removal of subtentorial structures. The SABRE component requires checking of image alignment along the anterior and posterior commissure (ACPC) plane, and identification of several anatomical landmarks required for regional parcellation. Finally, the Lesion-Seg component involves manual checking of the automatic lesion segmentation of subcortical hyperintensities (SH) for false positive errors.
While on-site training of the LE pipeline is preferable, readily available visual teaching tools with interactive training images are a viable alternative. Developed to ensure a high degree of accuracy and reliability, the following is a step-by-step, video-guided, standardized protocol for LE's manual procedures.

Lesion Explorer (LE) is a semi-automatic, image-processing pipeline developed to obtain regional brain tissue and subcortical hyperintensity lesion volumetrics from structural MRI of Alzheimer's disease and normal elderly. To ensure a high level of accuracy and reliability, the following is a video-guided, standardized protocol for LE's manual procedures.

Lesión Explorer: Un video-guiada, Protocolo normalizado para precisa y fiable volumétrica derivados de la RM en la Enfermedad de Alzheimer y normal Ancianos

Obtaining in vivo human brain tissue volumetrics from MRI is often complicated by various technical and biological issues. These challenges are ...

Excitotoxic Stimulation of Brain Microslices as an In vitro Model of Stroke

Examining molecular mechanisms involved in neuropathological conditions, such as ischemic stroke, can be difficult when using whole animal systems. As such, primary or &#39;neuronal-like&#39; cell culture systems are commonly utilized. While&#160;these systems are relatively easy to work with, and are useful model systems in which various functional outcomes (such as cell death) can be readily quantified, the examined outcomes and pathways in cultured immature neurons (such as excitotoxicity-mediated cell death pathways) are not necessarily the same as those observed in mature brain, or in intact tissue. Therefore, there is the need to develop models in which cellular mechanisms in mature neural tissue can be examined. We have developed an in vitro technique that can be used to investigate a variety of molecular pathways in intact nervous tissue. The technique described herein utilizes rat cortical tissue, but this technique can be adapted to use tissue from a variety of species (such as mouse, rabbit, guinea pig, and chicken) or brain regions (for example, hippocampus, striatum, etc.). Additionally, a variety of stimulations/treatments can be used (for example, excitotoxic, administration of inhibitors, etc.). In conclusion, the brain slice model described herein can be used to examine a variety of molecular mechanisms involved in excitotoxicity-mediated brain injury.

Excitotoxic Stimulation of Brain Microslices as an In vitro Model of Stroke

We have developed a brain slice model which can be used to examine molecular mechanisms involved in excitotoxicity-mediated brain injury.&#160;This technique generates viable mature brain tissue and reduces animal numbers required for experimentation, whilst keeping the neuronal circuitry, cellular interactions, and postsynaptic compartments partly intact.

Excitotóxica Estimulación del cerebro Microslices como<em&gt; In vitro</em&gt; Modelo de Carrera

Examining molecular mechanisms involved in neuropathological conditions, such as ischemic stroke, can be difficult when using whole animal systems. As ...

Controlling Parkinson's Disease With Adaptive Deep Brain Stimulation

Adaptive deep brain stimulation (aDBS) has the potential to improve the treatment of Parkinson&#39;s disease by optimizing stimulation in real time according to fluctuating disease and medication state. In the present realization of adaptive DBS we record and stimulate from the DBS electrodes implanted in the subthalamic nucleus of patients with Parkinson&#39;s disease in the early post-operative period. Local field potentials are analogue filtered between 3 and 47 Hz before being passed to a data acquisition unit where they are digitally filtered again around the patient specific beta peak, rectified and smoothed to give an online reading of the beta amplitude. A threshold for beta amplitude is set heuristically, which, if crossed, passes a trigger signal to the stimulator. The stimulator then ramps up stimulation to a pre-determined clinically effective voltage over 250 msec and continues to stimulate until the beta amplitude again falls down below threshold. Stimulation continues in this manner with brief episodes of ramped DBS during periods of heightened beta power.
Clinical efficacy is assessed after a minimum period of stabilization (5 min) through the unblinded and blinded video assessment of motor function using a selection of scores from the Unified Parkinson&#39;s Rating Scale (UPDRS). Recent work has demonstrated a reduction in power consumption with aDBS as well as an improvement in clinical scores compared to conventional DBS. Chronic aDBS could now be trialed in Parkinsonism.

Adaptive deep brain stimulation (aDBS) is effective for Parkinson&#8217;s disease, improving symptoms and reducing power consumption compared to conventional deep brain stimulation (cDBS). In aDBS we track a local field potential biomarker (beta oscillatory amplitude) in real time and use this to control the timing of stimulation.

El control de la enfermedad de Parkinson con Adaptive estimulación cerebral profunda

Adaptive deep brain stimulation (aDBS) has the potential to improve the treatment of Parkinson&#39;s disease by optimizing stimulation in real time ...

A Multimodal Imaging- and Stimulation-based Method of Evaluating Connectivity-related Brain Excitability in Patients with Epilepsy

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations over time in the blood-oxygenation level dependent signal. rs-fcMRI has been applied extensively to identify abnormalities in brain connectivity in different neurologic and psychiatric diseases. However, the relationship among rs-fcMRI connectivity abnormalities, brain electrophysiology and disease state is unknown, in part because the causal significance of alterations in functional connectivity in disease pathophysiology has not been established. Transcranial Magnetic Stimulation (TMS) is a technique that uses electromagnetic induction to noninvasively produce focal changes in cortical activity. When combined with electroencephalography (EEG), TMS can be used to assess the brain's response to external perturbations. Here we provide a protocol for combining rs-fcMRI, TMS and EEG to assess the physiologic significance of alterations in functional connectivity in patients with neuropsychiatric disease. We provide representative results from a previously published study in which rs-fcMRI was used to identify regions with abnormal connectivity in patients with epilepsy due to a malformation of cortical development, periventricular nodular heterotopia (PNH). Stimulation in patients with epilepsy resulted in abnormal TMS-evoked EEG activity relative to stimulation of the same sites in matched healthy control patients, with an abnormal increase in the late component of the TMS-evoked potential, consistent with cortical hyperexcitability. This abnormality was specific to regions with abnormal resting-state functional connectivity. Electrical source analysis in a subject with previously recorded seizures demonstrated that the origin of the abnormal TMS-evoked activity co-localized with the seizure-onset zone, suggesting the presence of an epileptogenic circuit. These results demonstrate how rs-fcMRI, TMS and EEG can be utilized together to identify and understand the physiological significance of abnormal brain connectivity in human diseases.

Resting-state functional-connectivity MRI has identified abnormalities in patients with a wide range of neuropsychiatric disorders, including epilepsy due to malformations of cortical development. Transcranial Magnetic Stimulation in combination with EEG can demonstrate that patients with epilepsy have cortical hyperexcitability in regions with abnormal connectivity.

Un método multimodal Imaging- y basados ​​en la estimulación de evaluar relacionados con la conectividad cerebral excitabilidad en pacientes con epilepsia

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations ...

Continuous IV Infusion is the Choice Treatment Route for Arginine-vasopressin Receptor Blocker Conivaptan in Mice to Study Stroke-evoked Brain Edema

Stroke is one of the major causes of morbidity and mortality in the world. Stroke is complicated by brain edema and other pathophysiological events. Among the most important players in the development and evolution of stroke-evoked brain edema is the hormone arginine-vasopressin and its receptors, V1a and V2. Recently, the V1a and V2 receptor blocker conivaptan has been attracting attention as a potential drug to reduce brain edema after stroke. However, animal models which involve conivaptan applications in stroke research need to be modified based on feasible routes of administration. Here the outcomes of 48 hr continuous intravenous (IV) are compared with intraperitoneal (IP) conivaptan treatments after experimental stroke in mice. We developed a protocol in which middle cerebral artery occlusion was combined with catheter installation into the jugular vein for IV treatment of conivaptan (0.2 mg) or vehicle. Different cohorts of animals were treated with 0.2 mg bolus of conivaptan or vehicle IP daily. Experimental stroke-evoked brain edema was evaluated in mice after continuous IV and IP treatments. Comparison of the results revealed that the continuous IV administration of conivaptan alleviates post-ischemic brain edema in mice, unlike the IP administration of conivaptan. We conclude that our model can be used for future studies of conivaptan applications in the context of stroke and brain edema.

Our studies have revealed that the beneficial effects of conivaptan are dependent on the method of delivery after experimental stroke in mice. We have developed a research protocol for delivery of the receptor blocker via IV catheter on stroke-evoked brain edema formation in mice.

La infusión intravenosa continua es la Ruta Opción de tratamiento para la arginina vasopresina-bloqueante del receptor Conivaptan en ratones para Stroke Study-evocó edema cerebral

Stroke is one of the major causes of morbidity and mortality in the world. Stroke is complicated by brain edema and other pathophysiological events. Among ...

Symmetric Bihemispheric Postmortem Brain Cutting to Study Healthy and Pathological Brain Conditions in Humans

Neuropathologists, at times, feel intimidated by the amount of knowledge needed to generate definitive diagnoses for complex neuropsychiatric phenomena described in those patients for whom a brain autopsy has been requested. Although the advancements of biomedical sciences and neuroimaging have revolutionized the neuropsychiatric field, they have also generated the misleading idea that brain autopsies have only a confirmatory value. This false idea created a drastic reduction of autopsy rates and, consequently, a reduced possibility to perform more detailed and extensive neuropathological investigations, which are necessary to comprehend numerous normal and pathological aspects yet unknown of the human brain. The traditional inferential method of correlation between observed neuropsychiatric phenomena and corresponding localization/characterization of their possible neurohistological correlates continues to have an undeniable value. In the context of neuropsychiatric diseases, the traditional clinicopathological method is still the best possible methodology (and often the only available) to link unique neuropsychiatric features to their corresponding neuropathological substrates, since it relies specifically upon the direct physical assessment of brain tissues. The assessment of postmortem brains is based on brain cutting procedures that vary across different neuropathology centers. Brain cuttings are performed in a relatively extensive and systematic way based on the various clinical and academic contingencies present in each institution. A more anatomically inclusive and symmetric bi-hemispheric brain cutting methodology should at least be used for research purposes in human neuropathology to coherently investigate, in depth, normal and pathological conditions with the peculiarities of the human brain (i.e., hemispheric specialization and lateralization for specific functions). Such a method would provide a more comprehensive collection of neuropathologically well-characterized brains available for current and future biotechnological and neuroimaging techniques. We describe a symmetric bi-hemispheric brain cutting procedure for the investigation of hemispheric differences in human brain pathologies and for use with current as well as future biomolecular/neuroimaging techniques.

Organized brain cutting procedures are necessary to correlate specific neuropsychiatric phenomena with definitive neuropathologic diagnoses. Brain cuttings are performed differently based on various clinico-academic contingencies. This protocol describes a symmetric bihemispheric brain cutting procedure to investigate hemispheric differences in human brain pathologies and to maximize current and future biomolecular/neuroimaging techniques.

Simétrica bihemisférica post-mortem del cerebro de corte para estudiar sana y patológica condiciones cerebrales en humanos

Neuropathologists, at times, feel intimidated by the amount of knowledge needed to generate definitive diagnoses for complex neuropsychiatric phenomena ...

Usando Saccadometry con estimulación cerebral profunda para estudiar la función cerebral normal y patológica

Resumen

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Intra-operatoria tareas comportamiento en seres humanos sometidos a cirugía Awake Estimulación Cerebral Profunda

Eye Tracking niños pequeños con autismo

Aislamiento de oligómeros de PrP soluble e insoluble en el cerebro humano normal

Una novela de alta resolución

Lesión Explorer: Un video-guiada, Protocolo normalizado para precisa y fiable volumétrica derivados de la RM en la Enfermedad de Alzheimer y normal Ancianos

Excitotóxica Estimulación del cerebro Microslices como

El control de la enfermedad de Parkinson con Adaptive estimulación cerebral profunda

Un método multimodal Imaging- y basados en la estimulación de evaluar relacionados con la conectividad cerebral excitabilidad en pacientes con epilepsia

La infusión intravenosa continua es la Ruta Opción de tratamiento para la arginina vasopresina-bloqueante del receptor Conivaptan en ratones para Stroke Study-evocó edema cerebral

Simétrica bihemisférica post-mortem del cerebro de corte para estudiar sana y patológica condiciones cerebrales en humanos

Usando Saccadometry con estimulación cerebral profunda para estudiar la función cerebral normal y patológica

Resumen

Explorar más videos

Capítulos en este video

Intra-operatoria tareas comportamiento en seres humanos sometidos a cirugía Awake Estimulación Cerebral Profunda

Eye Tracking niños pequeños con autismo

Aislamiento de oligómeros de PrP soluble e insoluble en el cerebro humano normal

Una novela de alta resolución

Lesión Explorer: Un video-guiada, Protocolo normalizado para precisa y fiable volumétrica derivados de la RM en la Enfermedad de Alzheimer y normal Ancianos

Excitotóxica Estimulación del cerebro Microslices como

El control de la enfermedad de Parkinson con Adaptive estimulación cerebral profunda

Un método multimodal Imaging- y basados ​​en la estimulación de evaluar relacionados con la conectividad cerebral excitabilidad en pacientes con epilepsia

La infusión intravenosa continua es la Ruta Opción de tratamiento para la arginina vasopresina-bloqueante del receptor Conivaptan en ratones para Stroke Study-evocó edema cerebral

Simétrica bihemisférica post-mortem del cerebro de corte para estudiar sana y patológica condiciones cerebrales en humanos

Un método multimodal Imaging- y basados en la estimulación de evaluar relacionados con la conectividad cerebral excitabilidad en pacientes con epilepsia