The Head-fixed Behaving Rat—Procedures and Pitfalls

This paper describes experimental techniques with head-fixed, operantly conditioned rodents that allow the control of stimulus presentation and tracking of motor output at hitherto unprecedented levels of spatio-temporal precision. Experimental procedures for the surgery and behavioral training are presented. We place particular emphasis on potential pitfalls using these procedures in order to assist investigators who intend to engage in this type of experiment. We argue that head-fixed rodent models, by allowing the combination of methodologies from molecular manipulations, intracellular electrophysiology, and imaging to behavioral measurements, will be instrumental in combining insights into the functional neuronal organization at different levels of observation. Provided viable behavioral methods are implemented, model systems based on rodents will be complementary to current primate models—the latter providing highest comparability with the human brain, while the former offer hugely advanced methodologies on the lower levels of organization, for example, genetic alterations, intracellular electrophysiology, and imaging

Physiological characterisation of transcranial magnetic stimulation (TMS) using functional magnetic resonance imaging (fMRI).

Despite its widespread use, a striking lack of knowledge exists regarding the mechanism of action of transcranial magnetic stimulation (TMS). This thesis describes the physiological characterisation of repetitive TMS (rTMS) to the motor system by means of functional magnetic resonance imaging (fMRI). A detailed analysis of imaging artefacts arising from the simultaneous application of TMS-fMRI was conducted and subsequently, strategies were presented for unperturbed TMS-fMRI. Physiological responses during subthreshold high-frequency rTMS of the primary sensorimotor cortex (Ml/Sl) were visualised within distinct cortical motor regions, comprising PMd, SMA, and contralateral Ml/Sl, while no significant responses were evidenced in the area of stimulation. Repetitive TMS during or before motor behaviour illustrated the context- dependence of rTMS-induced activity changes. The first demonstration of TMS-fMRI at 3 Tesla provided evidence that subthreshold rTMS can activate distinct networks including subcortical motor regions. The subthreshold nature of rTMS was confirmed by simultaneous electromyographic recordings from the target muscle. Stimulation of the dorsal premotor cortex provided evidence that rTMS- evoked local activity changes depend on the input function. The capability of TMS to target distinct networks in the human brain was confirmed. TMS targets a set of cortical and subcortical structures. Local responses may not invariably be elicited, indicating that low levels of synaptic activity, as occurring at low-intensity stimulation, do not necessarily evoke corresponding changes in cortical haemodynamics. It is concluded that combined TMS-fMRI offers a means to assess the mechanism of action of TMS at high spatial and temporal resolution

Development and assessment of a hand assist device: GRIPIT

Background Although various hand assist devices have been commercialized for people with paralysis, they are somewhat limited in terms of tool fixation and device attachment method. Hand exoskeleton robots allow users to grasp a wider range of tools but are heavy, complicated, and bulky owing to the presence of numerous actuators and controllers. The GRIPIT hand assist device overcomes the limitations of both conventional devices and exoskeleton robots by providing improved tool fixation and device attachment in a lightweight and compact device. GRIPIT has been designed to assist tripod grasp for people with spinal cord injury because this grasp posture is frequently used in school and offices for such activities as writing and grasping small objects. Methods The main development objective of GRIPIT is to assist users to grasp tools with their own hand using a lightweight, compact assistive device that is manually operated via a single wire. GRIPIT consists of only a glove, a wire, and a small structure that maintains tendon tension to permit a stable grasp. The tendon routing points are designed to apply force to the thumb, index finger, and middle finger to form a tripod grasp. A tension-maintenance structure sustains the grasp posture with appropriate tension. Following device development, four people with spinal cord injury were recruited to verify the writing performance of GRIPIT compared to the performance of a conventional penholder and handwriting. Writing was chosen as the assessment task because it requires a tripod grasp, which is one of the main performance objectives of GRIPIT. Results New assessment, which includes six different writing tasks, was devised to measure writing ability from various viewpoints including both qualitative and quantitative methods, while most conventional assessments include only qualitative methods or simple time measuring assessments. Appearance, portability, difficulty of wearing, difficulty of grasping the subject, writing sensation, fatigability, and legibility were measured to assess qualitative performance while writing various words and sentences. Results showed that GRIPIT is relatively complicated to wear and use compared to a conventional assist device but has advantages for writing sensation, fatigability, and legibility because it affords sufficient grasp force during writing. Two quantitative performance factors were assessed, accuracy of writing and solidity of writing. To assess accuracy of writing, we asked subjects to draw various figures under given conditions. To assess solidity of writing, pen tip force and the angle variation of the pen were measured. Quantitative evaluation results showed that GRIPIT helps users to write accurately without pen shakes even high force is applied on the pen. Conclusions Qualitative and quantitative results were better when subjects used GRIPIT than when they used the conventional penholder, mainly because GRIPIT allowed them to exert a higher grasp force. Grasp force is important because disabled people cannot control their fingers and thus need to move their entire arm to write, while non-disabled people only need to move their fingers to write. The tension-maintenance structure developed for GRIPIT provides appropriate grasp force and moment balance on the users hand, but the other writing method only fixes the pen using friction force or requires the users arm to generate a grasp force

ヒトの高周波振動知覚の類似特性に基づく触覚変調

Tohoku University昆陽雅司課

Modelling and analysis of neurons coupled by electrical synapses

The objective of this thesis is to analyze the role of the intrinsic properties of neurons in the communication through electrical synapses. Mesencephalic trigeminal neurons constitute an excellent experimental model to study the communication between neurons, because of its easy experimental access experimental and simple to model and analyze a biological system. Among the contributions of this thesis are: the complete modeling of the sodium currents and other ionic current (and its modulation); the explanation preference subthreshold frequency transfer between neuronfor example and its coupling. Some preliminary results of this work have been presented at international conferences.morphology. However, the analysis of real neurons is limited by experimental constraints that do not allow to explore all aspects of the model. Within the context of this thesis, a mathematical model is built, based on electrophysiological recordings made by Sebastián Curti at the School of Medicine of Universidad de la República. The model consists of a set of differential equations, which can be represented by a nonlinear electrical circuit. Some of the differential equations are obtained from literature and only some minor parameters’ adjustments are made. Moreover, during the thesis we have found that more data was needed in order to explain some of the most important features of the behavior of neurons, such as the duration of the action potential. Therefore, more experimental recordings were made, allowing to refine the model. The model allows to evaluate the response of the neuron to different stimuli (currents or voltages imposed by an electrode), making possible to make new “experiments” that are not possible in a laboratory. Alternatives models are analyzed (varying ionic currents and morphology) using experimental information to validate them. Then the model is used to understand some unusual features of the communication between neurons. First, it is studied the subthreshold transfer function (i.e. without action potentials) between neurons coupled by electrical synapses. A reduced model is used and then linearized, in order to derive an analytical expression of the transfer function, whose behaviour is consistent with experimental results. Moreover, numerical simulations are performed to analyze the rol of the intrinsic properties of neurons in their synchronization. It is shown that the same properties that determine the subthreshold behavior are relevant to improve synchronization between neurons too. Finally, this thesis contributes not only with new models and answers, but with new questions, which should be studied using experimental models as well. This thesis applies several tools used for electrical engineering (frequency response of systems, cable equation, Markov chains, evolutionary algorithms, etc.) to model and analyze a biological system. Among the contributions of this thesis are: the complete modeling of the sodium currents and other ionic current (and its modulation); the explanation preference subthreshold frequency transfer between neuronfor example and its coupling. Some preliminary results of this work have been presented at international conferences.El objetivo de esta tesis es analizar el rol de las propiedades intrínsecas de las neuronas en la comunicación a través de sinapsis eléctricas. Las neuronas del nervio trigeminal del mesencéfalo constituyen un excelente modelo experimental para estudiar la comunicación entre neuronas, debido a su fácil acceso experimental y su sencilla morfología. Sin embargo, el análisis de neuronas reales está limitado por restricciones experimentales que impiden explorar todos los aspectos del modelo. En el marco de esta tesis, se construye un modelo matemático basado en registros electrofisiológicos realizados por Sebastián Curti en la Facultad de Medicina de la Universidad de la República. El modelo consiste en un sistema de ecuaciones diferenciales, que puede ser representado por un circuito eléctrico con componentes no lineales. Algunas de las ecuaciones diferenciales son obtenidas de bibliografía y se realizan algunos ajustes menores de parámetros. Por otro lado, durante la tesis evaluamos que se necesitaba más información para reproducir algunas de las características más importantes del comportamientos de las neuronas, como la duración del potencial de acción. Por eso, se debieron realizar nuevos registros experimentales, que permitieron refinar el modelo. El modelo permite evaluar la respuesta de la neurona ante diferentes estímulos (corrientes o voltajes impuestos por un electrodo), posibilitando nuevos “experimentos” que no son posibles en un laboratorio. Se analizan diversas alternativas de modelado (variando corrientes iónicas y morfología) usando información experimental para validarlos. Luego, el modelo es utilizado para entender algunas características inusuales de la comunicación entre neuronas. En primer lugar, se estudia la transferencia subumbral (i.e.: sin potenciales de acción) entre neuronas acopladas por sinapsis eléctricas. Se utiliza un modelo reducido, que es linealizado para obtener una expresión analítica de la transferencia, cuyo comportamiento es coherente con los resultados experimentales. Asimismo, se realizan simulaciones numéricas para analizar el rol en la sincronización de las propiedades intrínsecas de las neuronas. Se muestra que las mismas propiedades que determinan el comportamiento subumbral son relevantes para mejorar la sincronización entre neuronas. Finalmente, esta tesis no sólo contribuye con nuevos modelos y respuestas, sino con nuevas preguntas, que deberán ser estudiadas usando modelos experimentales también. Esta tesis hace uso de diversas herramientas utilizadas por la ingeniería eléctrica (comportamiento en frecuencia de sistemas, ecuación del cable, cadenas de Markov, algoritmos evolutivos, etc) para modelar y analizar un sistema biológico. Se realizan diversos aportes, por ejemplo: modelado completo de las corrientes de sodio, así como de la modulación de otra corriente; explicación de la preferencia en frecuencia de la transferencia subumbral entre neuronas; estudio de la sincronización en función de las propiedades de los osciladores y de su acople. Algunos resultados preliminares de este trabajo han sido presentados en congresos internacionales

Design of a robotic transcranial magnetic stimulation system

Transcranial Magnetic Stimulation (TMS) is an excellent and non-invasive technique for studying the human brain. Accurate placement of the magnetic coil is required by this technique in order to induce a specific cortical activity. Currently, the coil is manually held in most of stimulation procedures, which does not achieve the precise clinical evaluation of the procedure. This thesis proposes a robotic TMS system to resolve these problems as a robot has excellent locating and holding capabilities. The proposed system can track in real-time the subject’s head position and simultaneously maintain a constant contact force between the coil and the subject’s head so that it does not need to be restrained and thus ensure the accuracy of the stimulation result. Requirements for the robotic TMS system are proposed initially base on analysis of a serial of TMS experiments on real subjects. Both hardware and software design are addressed according to these requirements in this thesis. An optical tracking system is used in the system for guiding and tracking the motion of the robot and inadvertent small movements of the subject’s head. Two methods of coordinate system registration are developed base on DH and Tsai-lenz’s method, and it is found that DH method has an improved accuracy (RMS error is 0.55mm). In addition, the contact force is controlled using a Force/Torque sensor; and a combined position and force tracking controller is applied in the system. This combined controller incorporates the position tracking and conventional gain scheduling force control algorithms to monitor both position and force in real-time. These algorithms are verified through a series of experiments. And it is found that the maximum position and force error are 3mm and 5N respectively when the subject moves at a speed of 20mm/s. Although the performance still needs to be improved to achieve a better system, the robotic system has shown the significant advantage compared with the manual TMS system. Keywords—Transcranial Magnetic Stimulation, Robot arm, Medical system, Calibration, TrackingEThOS - Electronic Theses Online ServiceGBUnited Kingdo