<p class="jove_content"&gt; Financiado Holandés NWO / ZonMW subvenciones 912-03-037 y 911-02-004.</p

1. Plataforma Motion 6DF Estímulos vestibulares fueron entregados con una plataforma de movimiento (ver Figura 1) capaz de generar estímulos angular y de traslación en un total de seis grados de libertad (FCS-MOOG, Nieuw-Vennep, Países Bajos). La plataforma es movida por seis actuadores electro-mecánicos conectados a un ordenador personal con software de control dedicado. Se genera movimientos precisos con seis grados de libertad. Sensores colocados en los actuadores de control permanente del perfil de movimiento de la plataforma. El dispositivo cuenta con &lt;0.5 mm de precisión lineal y &lt;0,05 ° para los movimientos angulares. Vibraciones durante la estimulación fueron 0.02 °. Frecuencia de resonancia del dispositivo fue&gt; 75 Hz. Perfil de movimiento de la plataforma se reconstruye a partir de la información del sensor en los actuadores por medio de la dinámica inversa y se envía a la computadora de la colección de datos. Para sincronizar la plataforma y los datos de movimiento de los ojos, un rayo láser se monta en la parte trasera de la plaTForm y proyectado en una pequeña célula fotoeléctrica (1 mm, tiempo de reacción de 10 microsegundos). La tensión de salida de la fotocélula se tomaron muestras a una velocidad de 1 KHz junto con los datos del movimiento del ojo y proporciona un indicador de tiempo real de inicio de movimiento con 1 mseg exactitud. Durante el análisis fuera de línea usando Matlab (Mathworks, Natick, MA), el perfil de movimiento reconstruido de la plataforma sobre la base de la información del sensor de los actuadores en la plataforma fue alineado precisamente con el inicio de movimiento de la plataforma. 2. Sujetos A. Seating Los sujetos están sentados en una silla montada en el centro de la plataforma (Figura 2). El cuerpo del sujeto fue restringido con un cinturón de seguridad de cuatro puntos tal como se utiliza en los coches de carreras. Los cinturones de seguridad se anclaron a la base de la plataforma de movimiento. La silla estaba rodeada por un marco cúbico PVC y sirvió como soporte de las bobinas de campo. El sistema de bobina de campo era ajustable en altura, de tal manera que la SubjLos ojos de ect estaban en el centro del campo magnético. B. fijación Head La cabeza se inmoviliza utilizando una tabla de mordida-impresión moldeada individualmente, que fue unido al bastidor cúbico a través de una barra rígida. Un vacío almohada doblada alrededor del cuello y un anillo adjunto a la presidencia aseguró además la fijación del sujeto (Figura 1). Además, para vigilar los movimientos de la cabeza falsas durante la estimulación, atamos dos sensores 3D (Analog Devices Inc, Norwood, MA) directamente a la Junta mordida, una para angular y otra para aceleraciones lineales. 3. Sistema de coordenadas Rotaciones del ojo se definen en un sistema de coordenadas de mano derecha de cabeza fija (Figura 3). En este sistema desde el punto de vista de una rotación hacia la izquierda sobre el eje Z (guiñada), una rotación hacia abajo sobre el eje Y (tono) y la rotación hacia la derecha sobre el eje X (rollo) del sujeto se definen como positiVE. Los planos ortogonales a los ejes X, Y y Z ejes de rotación son, respectivamente, los planos de cabeceo, alabeo y guiñada (Figura 3). 4. Eye Movement Grabaciones Los movimientos oculares de ambos ojos fueron grabadas con bobinas de búsqueda esclerales 3D (Skalar, Delft, Países Bajos) 4 kHz utilizando un sistema de bobinas estándar de 25 dos de campo basado en el método de detección de amplitud de Robinson (Modelo EMP3020, Skalar Médico, Delft, Países Bajos) 5. Se han adoptado las señales de las bobinas a través de un filtro de paso bajo analógico con frecuencia de corte de 500 Hz y un muestreo de línea y almacenados en el disco duro a una frecuencia de 1 kHz con 16 bits de precisión (sistema CED Spike2 corriendo v6, Cambridge Electronic Design , Cambridge). 5. Bobina de calibración Antes de los experimentos, la sensibilidad y la no ortogonalidad de dirección y de torsión bobinas se verificó in vitro por el montaje de la bobina en un Fick gisistema de MBAL coloca en el centro del campo magnético. Mediante la rotación del sistema de cardán sobre todos los ejes cardinales se verificó que todas las bobinas utilizadas en los experimentos eran simétricas para todas las direcciones dentro de 2%. In vivo, las señales horizontales y verticales de las dos bobinas se calibraron individualmente por instruir al objeto de fijar sucesivamente una serie de cinco objetivos (objetivo central y un blanco a 10 grados a la izquierda, derecha, arriba y abajo) durante cinco segundos cada uno. Se proyectaron los objetivos de calibración en una pantalla translúcida a 186 cm de distancia. El análisis post experimento de los datos de calibración se tradujo en la sensibilidad y los valores de las bobinas de búsqueda cada desplazamiento. Estos valores se utilizaron a continuación en los procedimientos de análisis de escritos en Matlab 3. 6 Estimulación A. estimulación sinusoidal La plataforma de entrega rotaciones sinusoidales de todo el cuerpo (1 Hz, A = 4 °) sobre los tres cardinales ejes: el eje rostral caudal o vertical (guiñada), del eje interaural (tono) y el eje nasal-occipital (rodillo), y sobre ejes horizontales intermedios incrementados en pasos de 22,5 ° entre balanceo y cabeceo. Estímulos sinusoidales fueron entregados a la luz y la oscuridad. A la luz, temas fijos en un objetivo visual continuamente encendido (el LED rojo, 2 mm de diámetro), ubicado 177 cm delante del sujeto a nivel del ojo (Figura 1C panel izquierdo). Head se coloca de manera que la línea de Reid fue base (la línea imaginaria que une el meato externa con el cantus orbital inferior) estaba dentro de los 6 grados de la tierra-horizontal). Durante la estimulación sinusoidal en la oscuridad, el objetivo visual se presenta brevemente (2 segundos) cuando la plataforma estaba estacionario durante cada intervalo entre dos estímulos consecutivos. Para evitar los movimientos oculares espontáneos durante la estimulación, los sujetos fueron instruidos para fijar la ubicación imaginaria del objetivo fijo espacio durante sinusoideal estímulo después de que el objetivo había sido apagado justo antes de la aparición de movimiento. Hemos verificado que el tipo de instrucción reduce principalmente los movimientos oculares realizadas en la oscuridad, y tuvo sólo un pequeño efecto sobre la ganancia (&lt;10%). Esta variabilidad se produjo en todos los componentes (horizontal, vertical y de torsión) de forma simultánea. B. estimulación Impulse Corta duración impulsos de todo el cuerpo se entregan en un entorno con poca luz. El único estímulo visible a disposición del sujeto era un objetivo visual situada en 177 cm delante del sujeto a nivel de los ojos. Cada impulso se repitió seis veces y se entrega en orden aleatorio y con la sincronización aleatoria de inicio de movimiento (intervalos variaron entre 2,5 y 3,5 segundos). El perfil de los impulsos fue una aceleración constante de 100 ° seg -2 durante la primera 100 mseg del impulso, seguido de una disminución gradual lineal en la aceleración. Este estímulo resultó en un aumento lineal en la velocidad alcanzando un VELOCdad de 10 ° s -1 después de 100 ms. Movimientos de la cabeza aberrantes durante la estimulación vestibular medidos por los dispositivos de aceleración lineal de velocidad angular y fueron menos de 4% de la amplitud del estímulo. La velocidad pico de los movimientos de los ojos en respuesta a estos impulsos era 100 veces por encima del nivel de ruido de las señales de las bobinas. 7. Análisis de Datos Señales de las bobinas se convierten en ángulos de Fick y luego expresan como vectores de giro 6,7. A partir de los datos de fijación del objetivo hacia delante se determinó la falta de alineación de la bobina en el ojo en relación con las bobinas de campo magnético primario ortogonales. Las señales fueron corregidos para este desalineamiento del eje de rotación en sentido contrario en tres dimensiones. También se verificó que ningún deslizamiento bobina se había producido durante el experimento mediante la verificación de la salida de la posición durante la fijación del objetivo antes de cada inicio de movimiento. Para expresar los movimientos del ojo en 3D en el dominio de la velocidad,convertimos los datos del vector de rotación de vuelta a la velocidad angular. Antes de la conversión del vector de la rotación a la velocidad angular, que regularizaba los datos de fase cero con un filtro digital de avance y retroceso con una ventana gaussiana de 20 puntos (longitud de 20 ms). 8. Respuestas sinusoidales Una ganancia. La ganancia de cada componente y 3D ganancia de velocidad de ojo se calculó mediante la instalación de una sinusoide con una frecuencia igual a la frecuencia de la plataforma a través de los componentes de la velocidad angular horizontales, verticales y de torsión. La ganancia para cada componente se define como la relación entre el ojo componente de la velocidad pico y la velocidad de pico plataforma se calculó por separado para cada ojo. La desalineación B. La desalineación entre el eje de velocidad ojo 3D y el eje velocidad de la cabeza se calculó mediante el enfoque de Aw et al 8,9. A partir del producto escalar de dos vectores de la desalineación se calculó como la instantaneous ángulo en tres dimensiones entre la inversa de la velocidad del eje del ojo y el eje de velocidad de la cabeza. El aumento de la velocidad angular y la desalineación 3D para cada orientación azimutal se compararon con la ganancia y la desalineación predicho a partir del vector suma de los 0 ° (rollo) y 90 ° (tono) acimut componentes 10. A partir de este vector suma se deduce que cuando las ganancias de velocidad de balanceo y cabeceo son iguales, la orientación del eje de rotación del ojo se alinea con el eje de rotación de la cabeza, cuando los dos son diferentes, se espera que la desviación máxima entre el estímulo y el eje de rotación del ojo en 45 ° acimut. 9. Impulse Responses Izquierda y derecha huellas datos oculares de seis presentaciones para cada dirección de movimiento se analizaron por separado. Debido a que los valores de los ojos izquierdo y derecho son casi idénticos, los datos del ojo izquierdo y derecho se promedian para determinar la ganancia de la velocidad del ojo en respuesta a la estimulación impulso. Todos los rastros fueroninspeccionados individualmente en la pantalla de un ordenador. Cuando el sujeto realizó un abrir y cerrar o sacada durante el impulso que trace se descartó de forma manual. Componentes de la velocidad angular (N = 5 a 6) durante los primeros 100 ms después de la aparición del movimiento se promediaron en los contenedores de tiempo de 20 ms (proporcionar un filtrado de paso bajo efectivo) y se representan en función de la velocidad de la plataforma 11,12.

<ol>
	<li>Houben, M. M. J., Goumans, J., Dejongste, A. H., Van der Steen, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Angular+and+linear+vestibulo-ocular+responses+in+humans.">Angular and linear vestibulo-ocular responses in humans.</a> Ann. N.Y. Acad. Sci. 1039, 68-80 (2005).</li><li>Collewijn, H., Van der Steen, J., Ferman, L., Jansen, T. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Human+ocular+counterroll:+assessment+of+static+and+dynamic+properties+from+electromagnetic+scleral+coil+recordings.">Human ocular counterroll: assessment of static and dynamic properties from electromagnetic scleral coil recordings.</a> Exp. Brain Res. 59, 185-196 (1985).</li><li>Goumans, J., Houben, M. M., Dits, J., Van der Steen, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Peaks+and+troughs+of+three-dimensional+vestibulo-ocular+reflex+in+humans.">Peaks and troughs of three-dimensional vestibulo-ocular reflex in humans.</a> J. Assoc. Res. Otolaryngol. 11, 383-393 (2010).</li><li>Ferman, L., Collewijn, H., Jansen, T. C., Vanden Berg, A. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Human+gaze+stability+in+the+horizontal,+vertical+and+torsional+direction+during+voluntary+head+movements,+evaluated+with+a+three-dimensional+scleral+induction+coil+technique.">Human gaze stability in the horizontal, vertical and torsional direction during voluntary head movements, evaluated with a three-dimensional scleral induction coil technique.</a> Vision Res. 27, 811-828 (1987).</li><li>Robinson, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Method+of+Measuring+Eye+Movement+Using+a+Scleral+Search+Coil+in+a+Magnetic+Field.">A Method of Measuring Eye Movement Using a Scleral Search Coil in a Magnetic Field.</a> IEEE Trans. Biomed. Eng. 10, 137-145 (1963).</li><li>Haustein, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Considerations+on+Listing's+Law+and+the+primary+position+by+means+of+a+matrix+description+of+eye+position+control.">Considerations on Listing's Law and the primary position by means of a matrix description of eye position control.</a> Biol. Cybern. 60, 411-420 (1989).</li><li>Haslwanter, T., Moore, S. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+theoretical+analysis+of+three-dimensional+eye+position+measurement+using+polar+cross-correlation.">A theoretical analysis of three-dimensional eye position measurement using polar cross-correlation.</a> IEEE Trans. Biomed. Eng. 42, 1053-1061 (1995).</li><li>Aw, S. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Three-dimensional+vector+analysis+of+the+human+vestibuloocular+reflex+in+response+to+high-acceleration+head+rotations.+II.+responses+in+subjects+with+unilateral+vestibular+loss+and+selective+semicircular+canal+occlusion.">Three-dimensional vector analysis of the human vestibuloocular reflex in response to high-acceleration head rotations. II. responses in subjects with unilateral vestibular loss and selective semicircular canal occlusion.</a> J. Neurophysiol. 76, 4021-4030 (1996).</li><li>Aw, S. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Three-dimensional+vector+analysis+of+the+human+vestibuloocular+reflex+in+response+to+high-acceleration+head+rotations.+I.+Responses+in+normal+subjects.">Three-dimensional vector analysis of the human vestibuloocular reflex in response to high-acceleration head rotations. I. Responses in normal subjects.</a> J. Neurophysiol. 76, 4009-4020 (1996).</li><li>Crawford, J. D., Vilis, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Axes+of+eye+rotation+and+Listing's+law+during+rotations+of+the+head.">Axes of eye rotation and Listing's law during rotations of the head.</a> J. Neurophysiol. 65, 407-423 (1991).</li><li>Tabak, S., Collewijn, H., Boumans, L. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deviation+of+the+subjective+vertical+in+long-standing+unilateral+vestibular+loss.">Deviation of the subjective vertical in long-standing unilateral vestibular loss.</a> Acta. Otolaryngol. 117, 1-6 (1997).</li><li>Tabak, S., Collewijn, H., Boumans, L. J., Van der Steen, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gain+and+delay+of+human+vestibulo-ocular+reflexes+to+oscillation+and+steps+of+the+head+by+a+reactive+torque+helmet.+II.+Vestibular-deficient+subjects.">Gain and delay of human vestibulo-ocular reflexes to oscillation and steps of the head by a reactive torque helmet. II. Vestibular-deficient subjects.</a> Acta. Otolaryngol. 117, 796-809 (1997).</li><li>Van der Steen, J., Collewijn, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ocular+stability+in+the+horizontal,+frontal+and+sagittal+planes+in+the+rabbit.">Ocular stability in the horizontal, frontal and sagittal planes in the rabbit.</a> Exp. Brain Res. 56, 263-274 (1984).</li><li>Seidman, S. H., Leigh, R. J., Tomsak, R. L., Grant, M. P., Dell'Osso, L. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dynamic+properties+of+the+human+vestibulo-ocular+reflex+during+head+rotations+in+roll.">Dynamic properties of the human vestibulo-ocular reflex during head rotations in roll.</a> Vision Res. 35, 679-689 (1995).</li><li>Seidman, S. H., Leigh, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+human+torsional+vestibulo-ocular+reflex+during+rotation+about+an+earth-vertical+axis.">The human torsional vestibulo-ocular reflex during rotation about an earth-vertical axis.</a> Brain Res. 504, 264-268 (1989).</li><li>Tweed, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rotational+kinematics+of+the+human+vestibuloocular+reflex.+I.+Gain+matrices.">Rotational kinematics of the human vestibuloocular reflex. I. Gain matrices.</a> J. Neurophysiol. 72, 2467-2479 (1994).</li><li>Tabak, S., Collewijn, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Human+vestibulo-ocular+responses+to+rapid,+helmet-driven+head+movements.">Human vestibulo-ocular responses to rapid, helmet-driven head movements.</a> Exp. Brain Res. 102, 367-378 (1994).</li><li>Paige, G. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Linear+vestibulo-ocular+reflex+(LVOR)+and+modulation+by+vergence.">Linear vestibulo-ocular reflex (LVOR) and modulation by vergence.</a> Acta. Otolaryngol. Suppl. 481, 282-286 (1991).</li><li>Halmagyi, G. M., Aw, S. T., Cremer, P. D., Curthoys, I. S., Todd, M. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impulsive+testing+of+individual+semicircular+canal+function.">Impulsive testing of individual semicircular canal function.</a> Ann. N.Y. Acad. Sci. 942, 192-200 (2001).</li><li>Tabak, S., Collewijn, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evaluation+of+the+human+vestibulo-ocular+reflex+at+high+frequencies+with+a+helmet,+driven+by+reactive+torque.">Evaluation of the human vestibulo-ocular reflex at high frequencies with a helmet, driven by reactive torque.</a> Acta. Otolaryngol. Suppl. 520 Pt. 1, 4-8 (1995).</li><li>Crawford, J. D., Vilis, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Axes+of+eye+rotation+and+Listing's+law+during+rotations+of+the+head.">Axes of eye rotation and Listing's law during rotations of the head.</a> J. Neurophysiol. 65, 407-423 (1991).</li><li>Migliaccio, A. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+three-dimensional+vestibulo-ocular+reflex+evoked+by+high-acceleration+rotations+in+the+squirrel+monkey.">The three-dimensional vestibulo-ocular reflex evoked by high-acceleration rotations in the squirrel monkey.</a> Exp. Brain Res. 159, 433-446 (2004).</li></ol>

No tenemos nada que revelar.

Este documento describe un método para medir con precisión VOR angular 3D en respuesta a las rotaciones de todo el cuerpo en los seres humanos. La ventaja del método es que da información cuantitativa acerca de la ganancia y la desalineación angular de VOR 3D en las tres dimensiones. El método es útil para la investigación fundamental y tiene también potencial valor clínico, por ejemplo para probar los pacientes con problemas del canal verticales o pacientes con problemas vestibulares centrales malos ...

<table border="1">
 <tbody>
		<tr>
			<td>Electric Motion Base MB-E-6DOF/24/1800KG * (Formerly E-CUE 624-1800)</td>
			<td>FCS-MOOG, Nieuw-Vennep, The Netherlands</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Magnetic field with detector, Model EMP3020</td>
			<td>Skalar Medical, Delft, The Netherlands</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>CED power 1401, running Spike2 v6</td>
			<td>Cambridge Electronic Design, Cambridge</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Electromagnetic search coils</td>
			<td>Chronos Vision, Berlin, Germany</td>
			<td></td>
			<td></td>
		</tr>
 </tbody>
	</table>

three dimensional vestibular ocular reflex testing using a six degrees of freedom motion platform

The vestibular organ is a sensor that measures angular and linear accelerations with six degrees of freedom (6DF). Complete or partial defects in the vestibular organ results in mild to severe equilibrium problems, such as vertigo, dizziness, oscillopsia, gait unsteadiness nausea and/or vomiting. A good and frequently used measure to quantify gaze stabilization is the gain, which is defined as the magnitude of compensatory eye movements with respect to imposed head movements. To test vestibular function more fully one has to realize that 3D VOR ideally generates compensatory ocular rotations not only with a magnitude (gain) equal and opposite to the head rotation but also about an axis that is co-linear with the head rotation axis (alignment). Abnormal vestibular function thus results in changes in gain and changes in alignment of the 3D VOR response.
Here we describe a method to measure 3D VOR using whole body rotation on a 6DF motion platform. Although the method also allows testing translation VOR responses 1, we limit ourselves to a discussion of the method to measure 3D angular VOR. In addition, we restrict ourselves here to description of data collected in healthy subjects in response to angular sinusoidal and impulse stimulation.
Subjects are sitting upright and receive whole-body small amplitude sinusoidal and constant acceleration impulses. Sinusoidal stimuli (f = 1 Hz, A = 4&deg;) were delivered about the vertical axis and about axes in the horizontal plane varying between roll and pitch at increments of 22.5&deg; in azimuth. Impulses were delivered in yaw, roll and pitch and in the vertical canal planes. Eye movements were measured using the scleral search coil technique 2. Search coil signals were sampled at a frequency of 1 kHz.
The input-output ratio (gain) and misalignment (co-linearity) of the 3D VOR were calculated from the eye coil signals 3.
Gain and co-linearity of 3D VOR depended on the orientation of the stimulus axis. Systematic deviations were found in particular during horizontal axis stimulation. In the light the eye rotation axis was properly aligned with the stimulus axis at orientations 0&deg; and 90&deg; azimuth, but gradually deviated more and more towards 45&deg; azimuth.
The systematic deviations in misalignment for intermediate axes can be explained by a low gain for torsion (X-axis or roll-axis rotation) and a high gain for vertical eye movements (Y-axis or pitch-axis rotation (see Figure 2). Because intermediate axis stimulation leads a compensatory response based on vector summation of the individual eye rotation components, the net response axis will deviate because the gain for X- and Y-axis are different.
In darkness the gain of all eye rotation components had lower values. The result was that the misalignment in darkness and for impulses had different peaks and troughs than in the light: its minimum value was reached for pitch axis stimulation and its maximum for roll axis stimulation.
Case Presentation
Nine subjects participated in the experiment. All subjects gave their informed consent. The experimental procedure was approved by the Medical Ethics Committee of Erasmus University Medical Center and adhered to the Declaration of Helsinki for research involving human subjects.
Six subjects served as controls. Three subjects had a unilateral vestibular impairment due to a vestibular schwannoma. The age of control subjects (six males and three females) ranged from 22 to 55 years. None of the controls had visual or vestibular complaints due to neurological, cardio vascular and ophthalmic disorders.
The age of the patients with schwannoma varied between 44 and 64 years (two males and one female). All schwannoma subjects were under medical surveillance and/or had received treatment by a multidisciplinary team consisting of an othorhinolaryngologist and a neurosurgeon of the Erasmus University Medical Center. Tested patients all had a right side vestibular schwannoma and underwent a wait and watch policy (Table 1; subjects N1-N3) after being diagnosed with vestibular schwannoma. Their tumors had been stabile for over 8-10 years on magnetic resonance imaging.

Luz estimulación sinusoidal Figura 4 (panel superior) muestra para el grupo de control de la ganancia media de las componentes de la velocidad angular horizontales, verticales y de torsión para todos los estímulos sinusoidales probados en el plano horizontal a la luz. Torsión fue máxima a 0 ° acimut, mientras que verticales tuvo su máximo a 90 °. Figura 5 muestra la ganancia de velocidad 3D ojo a la luz. La ganancia varió entre 0,99 ± 0,12 (pitch) y 0...

Watch this Scientific Journal Video about Three Dimensional Vestibular Ocular Reflex Testing Using a Six Degrees of Freedom Motion Platform at JoVE.com

Three Dimensional Vestibular Ocular Reflex Testing Using a Six Degrees of Freedom Motion Platform

Se describe un método para medir los reflejos oculares vestibulo tridimensionales (3D VOR) en humanos utilizando un período de seis grados de libertad (6DF) simulador de movimiento. La ganancia y la desalineación de la VOR angular 3D proporcionan una medida directa de la calidad de la función vestibular. Se proporcionan datos representativos sobre los sujetos sanos

Tridimensional vestibular Ocular Pruebas Reflex Con un Seis Grados de Plataforma Movimiento Libertad

The vestibular organ is a sensor that measures angular and linear accelerations with six degrees of freedom (6DF). Complete or partial defects in the ...

three-dimensional-vestibular-ocular-reflex-testing-using-six-degrees

Research

JoVE Journal

Neuroscience

15.8K vistas.  Erasmus MC. Se describe un método para medir los reflejos oculares vestibulo tridimensionales (3D VOR) en humanos utilizando un período de seis grados de libertad (6DF) simulador de movimiento. La ganancia y la desalineación de la VOR angular 3D proporcionan una medida directa de la calidad de la función vestibular. Se proporcionan datos representativos sobre los sujetos sanos

Video: Three Dimensional Vestibular Ocular Reflex Testing Using a Six Degrees of Freedom Motion Platform

MPI CyberMotion Simulator: Implementation of a Novel Motion Simulator to Investigate Multisensory Path Integration in Three Dimensions

Path integration is a process in which self-motion is integrated over time to obtain an estimate of one's current position relative to a starting point 1. Humans can do path integration based exclusively on visual 2-3, auditory 4, or inertial cues 5. However, with multiple cues present, inertial cues - particularly kinaesthetic - seem to dominate 6-7. In the absence of vision, humans tend to overestimate short distances (&lt;5 m) and turning angles (&lt;30&deg;), but underestimate longer ones 5. Movement through physical space therefore does not seem to be accurately represented by the brain.
Extensive work has been done on evaluating path integration in the horizontal plane, but little is known about vertical movement (see 3 for virtual movement from vision alone). One reason for this is that traditional motion simulators have a small range of motion restricted mainly to the horizontal plane. Here we take advantage of a motion simulator 8-9 with a large range of motion to assess whether path integration is similar between horizontal and vertical planes. The relative contributions of inertial and visual cues for path navigation were also assessed.
16 observers sat upright in a seat mounted to the flange of a modified KUKA anthropomorphic robot arm. Sensory information was manipulated by providing visual (optic flow, limited lifetime star field), vestibular-kinaesthetic (passive self motion with eyes closed), or visual and vestibular-kinaesthetic motion cues. Movement trajectories in the horizontal, sagittal and frontal planes consisted of two segment lengths (1st: 0.4 m, 2nd: 1 m; &plusmn;0.24 m/s2 peak acceleration). The angle of the two segments was either 45&deg; or 90&deg;. Observers pointed back to their origin by moving an arrow that was superimposed on an avatar presented on the screen.
Observers were more likely to underestimate angle size for movement in the horizontal plane compared to the vertical planes. In the frontal plane observers were more likely to overestimate angle size while there was no such bias in the sagittal plane. Finally, observers responded slower when answering based on vestibular-kinaesthetic information alone. Human path integration based on vestibular-kinaesthetic information alone thus takes longer than when visual information is present. That pointing is consistent with underestimating and overestimating the angle one has moved through in the horizontal and vertical planes respectively, suggests that the neural representation of self-motion through space is non-symmetrical which may relate to the fact that humans experience movement mostly within the horizontal plane.

An efficient way to gain insight into how humans navigate themselves in three dimensions is described. The method takes advantage of a motion simulator capable of moving observers in ways unattainable by traditional simulators. Results confirm that movement in the horizontal plane is underestimated, while vertical movement is overestimated.

MPI CyberMotion Simulator: Implementación de un simulador de movimiento Novela encargado de investigar la integración multisensorial ruta en tres dimensiones

Path integration is a process in which self-motion is integrated over time to obtain an estimate of one's current position relative to a starting point 1. ...

Investigación

Neurociencias

Protocol for Three-dimensional Confocal Morphometric Analysis of Astrocytes

As glial cells in the brain, astrocytes have diverse functional roles in the central nervous system. In the presence of harmful stimuli, astrocytes modify their functional and structural properties, a condition called reactive astrogliosis. Here, a protocol for assessment of the morphological properties of astrocytes is presented. This protocol includes quantification of 12 different parameters i.e. the surface area and volume of the tissue covered by an astrocyte (astrocyte territory), the entire astrocyte including branches, cell body, and nucleus, as well as total length and number of branches, the intensity of fluorescence immunoreactivity of antibodies used for astrocyte detection, and astrocyte density (number/1,000 &#181;m2). For this purpose three-dimensional (3D) confocal microscopic images were created, and 3D image analysis software such as Volocity 6.3 was used for measurements. Rat brain tissue exposed to amyloid beta1-40 (A&#946;1-40) with or without a therapeutic&#160;intervention was used to present the method. This protocol can also be used for 3D morphometric analysis of other cells from either in vivo or in vitro conditions.

Astrocytes in the CNS change their functional and structural properties in response to harmful stimuli. This report presents a protocol for assessment of three-dimensional astrocyte morphology in diseased conditions or after therapeutic interventions.

Protocolo para tridimensional confocal morfométrico Análisis de astrocitos

As glial cells in the brain, astrocytes have diverse functional roles in the central nervous system. In the presence of harmful stimuli, astrocytes modify ...

A Rat Model of Central Fatigue Using a Modified Multiple Platform Method

In this article, we introduced a rat model of central fatigue using the modified multiple platform method (MMPM). The Multiple Platform box was designed as a water tank with narrow platforms on the bottom. The model rats were put into the tank and stood on the platforms for 14 h (18:00 - 8:00) per day for a consecutive 21 days, with a blank control group set for contrast. At the end of modeling, rats in the model group showed an obvious fatigued appearance. To assess the model, we performed several behavioral tests, including the open field test (OFT), the elevated plus maze (EPM) test, and the exhaustive swimming (ES) test. The results showed that anxiety, spatial cognition impairment, poor muscle performance, and declined voluntary activity presented in model rats confirm the diagnosis of&#160;central fatigue. Changes of the central neurotransmitters also verified the result. In conclusion, the model successfully simulated central fatigue, and future study with the model may help reveal the pathological mechanism of the disease.

Here, we present a protocol to introduce a rat model of central fatigue using the modified multiple platform method (MMPM).

Modelo de una rata de la fatiga Central mediante la método de plataforma múltiple

In this article, we introduced a rat model of central fatigue using the modified multiple platform method (MMPM). The Multiple Platform box was designed ...

Large-scale Three-dimensional Imaging of Cellular Organization in the Mouse Neocortex

The mammalian neocortex is composed of many types of excitatory and inhibitory neurons, each with specific electrophysiological and biochemical properties, synaptic connections, and in vivo functions, but their basic functional and anatomical organization from cellular to network scale is poorly understood. Here we describe a method for the three-dimensional imaging of fluorescently-labeled neurons across large areas of the brain for the investigation of the cortical cellular organization. Specific types of neurons are labeled by the injection of fluorescent retrograde neuronal tracers or expression of fluorescent proteins in transgenic mice. Block brain samples, e.g., a hemisphere, are prepared after fixation, made transparent with tissue clearing methods, and subjected to fluorescent immunolabeling of the specific cell types. Large areas are scanned using confocal or two-photon microscopes equipped with large working distance objectives and motorized stages. This method can resolve the periodic organization of the cell type-specific microcolumn functional modules in the mouse neocortex. The procedure can be useful for the study of three-dimensional cellular architecture in the diverse brain areas and other complex tissues.

Here we describe a procedure for tissue clearing, fluorescent labeling, and large-scale imaging of mouse brain tissue which, thereby, enables visualization of the three-dimensional organization of cell types in the neocortex.

Proyección de imagen tridimensional a gran escala de la organización celular en el Neocortex de ratón

The mammalian neocortex is composed of many types of excitatory and inhibitory neurons, each with specific electrophysiological and biochemical ...

Three-Dimensional Shape Modeling and Analysis of Brain Structures

Statistical shape analysis of brain structures has been used to investigate the association between their structural changes and pathological processes. We have developed a software package for accurate and robust shape modeling and group-wise analysis. Here, we introduce an pipeline for the shape analysis, from individual 3D shape modeling to quantitative group shape analysis. We also describe the pre-processing and segmentation steps using open software packages. This practical guide would help researchers save time and effort in 3D shape analysis on brain structures.

We introduce a semi-automatic protocol for shape analysis on brain structures, including image segmentation using open software, and further group-wise shape analysis using an automated modeling package. Here, we demonstrate each step of the 3D shape analysis protocol with hippocampal segmentation from brain MR images.

Modelado de formas tridimensionales y análisis de estructuras cerebrales

Statistical shape analysis of brain structures has been used to investigate the association between their structural changes and pathological processes. ...

In Vivo Three-Dimensional Two-Photon Microscopy to Study Conducted Vascular Responses by Local ATP Ejection Using a Glass Micro-Pipette

Maintenance of normal brain function requires a sufficient and efficient supply of oxygen and nutrition by a complex network of vessels. However, the regulation of cerebral blood flow (CBF) is incompletely understood, especially at the capillary level. Two-photon microscopy is a powerful tool widely used to study CBF and its regulation. Currently, this field is limited by the lack of in vivo two-photon microscopy studies examining (1) CBF responses in three-dimensions, (2) conducted vascular responses, and (3) localized interventions within the vascular network. Here, we describe a 3D in vivo method using two-photon microscopy to study conducted vascular responses elicited by&#160;local ejection of ATP with a glass micro-pipette. Our method uses fast and repetitive hyperstack two-photon imaging providing precise diameter measurements by maximal intensity projection of the obtained images. Furthermore, we show that this method can also be used to study 3D astrocytic calcium responses. We also discuss the advantages and limitations of glass micro-pipette insertion and two-photon hyperstack imaging.

We present an optimized local ejection procedure using a glass micro-pipette and a fast two-photon hyperstack imaging method, which allows precise measurement of capillary diameter changes and investigation of its regulation in three dimensions.

En Vivo Microscopía bicolor tridimensional para estudiar las respuestas vasculares realizadas por la eyección ATP local utilizando una micro-pipette de vidrio

Maintenance of normal brain function requires a sufficient and efficient supply of oxygen and nutrition by a complex network of vessels. However, the ...

Three-Dimensional Motor Nerve Organoid Generation

A fascicle of axons is one of the major structural motifs observed in the nervous system. Disruption of axon fascicles could cause developmental and neurodegenerative diseases. Although numerous studies of axons have been conducted, our understanding of formation and dysfunction of axon fascicles is still limited due to the lack of robust three-dimensional in vitro models. Here, we describe a step-by-step protocol for the rapid generation of a motor nerve organoid (MNO) from human induced pluripotent stem (iPS) cells in a microfluidic-based tissue culture chip. First, fabrication of chips used for the method is described. From human iPS cells, a motor neuron spheroid (MNS) is formed. Next, the differentiated MNS is transferred into the chip. Thereafter, axons spontaneously grow out of the spheroid and assemble into a fascicle within a microchannel equipped in the chip, which generates an MNO tissue carrying a bundle of axons extended from the spheroid. For the downstream analysis, MNOs can be taken out of the chip to be fixed for morphological analyses or dissected for biochemical analyses, as well as calcium imaging and multi-electrode array recordings. MNOs generated with this protocol can facilitate drug testing and screening and can contribute to understanding of mechanisms underlying development and diseases of axon fascicles.

This protocol provides a comprehensive procedure to fabricate human iPS cell-derived motor nerve organoid through spontaneous assembly of a robust bundle of axons extended from a spheroid in a tissue culture chip.

Generación de organoides nerviosos motores tridimensionales

A fascicle of axons is one of the major structural motifs observed in the nervous system. Disruption of axon fascicles could cause developmental and ...

Measuring the Influence of Magnetic Vestibular Stimulation on Nystagmus, Self-Motion Perception, and Cognitive Performance in a 7T MRT

Strong magnetic fields induce dizziness, vertigo, and nystagmus due to Lorentz forces acting on the cupula in the semi-circular canals, an effect called magnetic vestibular stimulation (MVS). In this article, we present an experimental setup in a 7T MRT scanner (MRI scanner) that allows the investigation of the influence of strong magnetic fields on nystagmus as well as perceptual and cognitive responses. The strength of MVS is manipulated by altering the head positions of the participants. The orientation of the participants&#39; semicircular canals with respect to the static magnetic field is assessed by combining a 3D magnetometer and 3D constructive interference in steady-state (3D-CISS) images. This approach allows to account for intra- and inter-individual differences in participants&#8217; responses to MVS. In the future, MVS can be useful for clinical research, for example, in the investigation of compensatory processes in vestibular disorders. Furthermore, it could foster insights into the interplay between vestibular information and cognitive processes in terms of spatial cognition and the emergence of self-motion percepts under conflicting sensory information. In fMRI studies, MVS can elicit a possible confounding effect, especially in tasks influenced by vestibular information or in studies comparing vestibular patients with healthy controls.

In this article, we describe the experimental setup, material, and procedures to assess reflexive eye movements, self-motion perception, and cognitive tasks under magnetic vestibular stimulation, as well as the anatomical orientation of the vestibular organs, in a 7 Tesla Magnetic resonance tomography (7T-MRT) scanner.

Medición de la influencia de la estimulación vestibular magnética en el nistagmo, la percepción del automovimiento y el rendimiento cognitivo en un MRT 7T

Strong magnetic fields induce dizziness, vertigo, and nystagmus due to Lorentz forces acting on the cupula in the semi-circular canals, an effect called ...

Production of Human Neurogenin 2-Inducible Neurons in a Three-Dimensional Suspension Bioreactor

The derivation of neuronal lineage cells from human induced pluripotent stem cells (hiPSCs) marked a milestone in brain research. Since their first advent, protocols have been continuously optimized and are now widely used in research and drug development. However, the very long duration of these conventional differentiation and maturation protocols and the increasing demand for high-quality hiPSCs and their neural derivatives raise the need for the adoption, optimization, and standardization of these protocols to large-scale production. This work presents a fast and efficient protocol for the differentiation of genetically modified, doxycycline-inducible neurogenin 2 (iNGN2)-expressing hiPSCs into neurons using a benchtop three-dimensional (3D) suspension bioreactor.
In brief, single-cell suspensions of iNGN2-hiPSCs were allowed to form aggregates within 24 h, and neuronal lineage commitment was induced by the addition of doxycycline. Aggregates were dissociated after 2 days of induction and cells were either cryopreserved or replated for terminal maturation. The generated iNGN2 neurons expressed classical neuronal markers early on and formed complex neuritic networks within 1 week after replating, indicating an increasing maturity of neuronal cultures. In summary, a detailed step-by-step protocol for the fast generation of hiPSC-derived neurons in a 3D environment is provided that holds great potential as a starting point for disease modeling, phenotypic high-throughput drug screenings, and large-scale toxicity testing.

This article describes a protocol for the generation of human induced pluripotent stem cell-derived neurons in a benchtop 3D suspension bioreactor.

Producción de neuronas humanas inducibles por neurogenina 2 en un biorreactor de suspensión tridimensional

The derivation of neuronal lineage cells from human induced pluripotent stem cells (hiPSCs) marked a milestone in brain research. Since their first ...

In vivo Imágenes de todo el cerebro de larvas de pez cebra

In Vivo Whole-Brain Imaging of Zebrafish Larvae Using Three-Dimensional Fluorescence Microscopy

As a vertebrate model animal, larval zebrafish are widely used in neuroscience and provide a unique opportunity to monitor whole-brain activity at the cellular resolution. Here, we provide an optimized protocol for performing whole-brain imaging of larval zebrafish using three-dimensional fluorescence microscopy, including sample preparation and immobilization, sample embedding, image acquisition, and visualization after imaging. The current protocol enables in vivo imaging of the structure and neuronal activity of a larval zebrafish brain at a cellular resolution for over 1 h using confocal microscopy and custom-designed fluorescence microscopy. The critical steps in the protocol are also discussed, including sample mounting and positioning, preventing bubble formation and dust in the agarose gel, and avoiding motion in images caused by incomplete solidification of the agarose gel and paralyzation of the fish. The protocol has been validated and confirmed in multiple settings. This protocol can be easily adapted for imaging other organs of a larval zebrafish.

Autor destacado: Imágenes in vivo de todo el cerebro de larvas de pez cebra utilizando microscopía de fluorescencia tridimensional  

Presented here is a protocol for in vivo whole-brain imaging of larval zebrafish using three-dimensional fluorescence microscopy. The experimental procedure includes sample preparation, image acquisition, and visualization.

In vivo Imágenes de todo el cerebro de larvas de pez cebra usando microscopía de fluorescencia tridimensional

As a vertebrate model animal, larval zebrafish are widely used in neuroscience and provide a unique opportunity to monitor whole-brain activity at the ...