Non-Penetrating Microelectrode Interfaces for Cortical Neuroprosthetic Applications with a Focus on Sensory Encoding: Feasibility and Chronic Performance in Striate Cortex

abstract: Growing understanding of the neural code and how to speak it has allowed for notable advancements in neural prosthetics. With commercially-available implantable systems with bi- directional neural communication on the horizon, there is an increasing imperative to develop high resolution interfaces that can survive the environment and be well tolerated by the nervous system under chronic use. The sensory encoding aspect optimally interfaces at a scale sufficient to evoke perception but focal in nature to maximize resolution and evoke more complex and nuanced sensations. Microelectrode arrays can maintain high spatial density, operating on the scale of cortical columns, and can be either penetrating or non-penetrating. The non-penetrating subset sits on the tissue surface without puncturing the parenchyma and is known to engender minimal tissue response and less damage than the penetrating counterpart, improving long term viability in vivo. Provided non-penetrating microelectrodes can consistently evoke perception and maintain a localized region of activation, non-penetrating micro-electrodes may provide an ideal platform for a high performing neural prosthesis; this dissertation explores their functional capacity. The scale at which non-penetrating electrode arrays can interface with cortex is evaluated in the context of extracting useful information. Articulate movements were decoded from surface microelectrode electrodes, and additional spatial analysis revealed unique signal content despite dense electrode spacing. With a basis for data extraction established, the focus shifts towards the information encoding half of neural interfaces. Finite element modeling was used to compare tissue recruitment under surface stimulation across electrode scales. Results indicated charge density-based metrics provide a reasonable approximation for current levels required to evoke a visual sensation and showed tissue recruitment increases exponentially with electrode diameter. Micro-scale electrodes (0.1 – 0.3 mm diameter) could sufficiently activate layers II/III in a model tuned to striate cortex while maintaining focal radii of activated tissue. In vivo testing proceeded in a nonhuman primate model. Stimulation consistently evoked visual percepts at safe current thresholds. Tracking perception thresholds across one year reflected stable values within minimal fluctuation. Modulating waveform parameters was found useful in reducing charge requirements to evoke perception. Pulse frequency and phase asymmetry were each used to reduce thresholds, improve charge efficiency, lower charge per phase – charge density metrics associated with tissue damage. No impairments to photic perception were observed during the course of the study, suggesting limited tissue damage from array implantation or electrically induced neurotoxicity. The subject consistently identified stimulation on closely spaced electrodes (2 mm center-to-center) as separate percepts, indicating sub-visual degree discrete resolution may be feasible with this platform. Although continued testing is necessary, preliminary results supports epicortical microelectrode arrays as a stable platform for interfacing with neural tissue and a viable option for bi-directional BCI applications.Dissertation/ThesisDoctoral Dissertation Biomedical Engineering 201

Decoding Neural Signals with Computational Models: A Systematic Review of Invasive BMI

There are significant milestones in modern human's civilization in which mankind stepped into a different level of life with a new spectrum of possibilities and comfort. From fire-lighting technology and wheeled wagons to writing, electricity and the Internet, each one changed our lives dramatically. In this paper, we take a deep look into the invasive Brain Machine Interface (BMI), an ambitious and cutting-edge technology which has the potential to be another important milestone in human civilization. Not only beneficial for patients with severe medical conditions, the invasive BMI technology can significantly impact different technologies and almost every aspect of human's life. We review the biological and engineering concepts that underpin the implementation of BMI applications. There are various essential techniques that are necessary for making invasive BMI applications a reality. We review these through providing an analysis of (i) possible applications of invasive BMI technology, (ii) the methods and devices for detecting and decoding brain signals, as well as (iii) possible options for stimulating signals into human's brain. Finally, we discuss the challenges and opportunities of invasive BMI for further development in the area.Comment: 51 pages, 14 figures, review articl

Algorithms for Neural Prosthetic Applications

abstract: In the last 15 years, there has been a significant increase in the number of motor neural prostheses used for restoring limb function lost due to neurological disorders or accidents. The aim of this technology is to enable patients to control a motor prosthesis using their residual neural pathways (central or peripheral). Recent studies in non-human primates and humans have shown the possibility of controlling a prosthesis for accomplishing varied tasks such as self-feeding, typing, reaching, grasping, and performing fine dexterous movements. A neural decoding system comprises mainly of three components: (i) sensors to record neural signals, (ii) an algorithm to map neural recordings to upper limb kinematics and (iii) a prosthetic arm actuated by control signals generated by the algorithm. Machine learning algorithms that map input neural activity to the output kinematics (like finger trajectory) form the core of the neural decoding system. The choice of the algorithm is thus, mainly imposed by the neural signal of interest and the output parameter being decoded. The various parts of a neural decoding system are neural data, feature extraction, feature selection, and machine learning algorithm. There have been significant advances in the field of neural prosthetic applications. But there are challenges for translating a neural prosthesis from a laboratory setting to a clinical environment. To achieve a fully functional prosthetic device with maximum user compliance and acceptance, these factors need to be addressed and taken into consideration. Three challenges in developing robust neural decoding systems were addressed by exploring neural variability in the peripheral nervous system for dexterous finger movements, feature selection methods based on clinically relevant metrics and a novel method for decoding dexterous finger movements based on ensemble methods.Dissertation/ThesisDoctoral Dissertation Bioengineering 201

Brain-machine interface using electrocorticography in humans

Paralysis has a severe impact on a patient’s quality of life and entails a high emotional burden and life-long social and financial costs. More than 5 million people in the USA suffer from some form of paralysis and about 50% of the people older than 65 experience difficulties or inabilities with movement. Restoring movement and communication for patients with neurological and motor disorders, stroke and spinal cord injuries remains a challenging clinical problem without an adequate solution. A brain-machine interface (BMI) allows subjects to control a device, such as a computer cursor or an artificial hand, exclusively by their brain activity. BMIs can be used to control communication and prosthetic devices, thereby restoring the communication and movement capabilities of the paralyzed patients. So far, most powerful BMIs have been realized by extracting movement parameters from the activity of single neurons. To record such activity, electrodes have to penetrate the brain tissue, thereby generating risk of brain injury. In addition, recording instability, due to small movements of the electrodes within the brain and the neuronal tissue response to the electrode implant, is also an issue. In this thesis, I investigate whether electrocorticography (ECoG), an alternative recording technique, can be used to achieve BMIs with similar accuracy. First, I demonstrate a BMI based on the approach of extracting movement parameters from ECoG signals. Such ECoG based BMI can further be improved using supervised adaptive algorithms. To implement such algorithms, it is necessary to continuously receive feedback from the subject whether the BMI-decoded trajectory was correct or incorrect. I show that, by using the same ECoG recordings, neuronal responses to trajectory errors can be recorded, detected and differentiated from other types of errors. Finally, I devise a method that could be used to improve the detection of error related neuronal responses

Advancing Pattern Recognition Techniques for Brain-Computer Interfaces: Optimizing Discriminability, Compactness, and Robustness

In dieser Dissertation formulieren wir drei zentrale Zielkriterien zur systematischen Weiterentwicklung der Mustererkennung moderner Brain-Computer Interfaces (BCIs). Darauf aufbauend wird ein Rahmenwerk zur Mustererkennung von BCIs entwickelt, das die drei Zielkriterien durch einen neuen Optimierungsalgorithmus vereint. Darüber hinaus zeigen wir die erfolgreiche Umsetzung unseres Ansatzes für zwei innovative BCI Paradigmen, für die es bisher keine etablierte Mustererkennungsmethodik gibt

The potential of error-related potentials. Analysis and decoding for control, neuro-rehabilitation and motor substitution

Las interfaces cerebro-máquina (BMIs, por sus siglas en inglés) permiten la decodificación de patrones de activación neuronal del cerebro de los usuarios para proporcionar a personas con movilidad severamente limitada, ya sea debido a un accidente o a una enfermedad neurodegenerativa, una forma de establecer una conexión directa entre su cerebro y un dispositivo. En este sentido, las BMIs basadas en técnicas no invasivas, como el electroencefalograma (EEG) han ofrecido a estos usuarios nuevas oportunidades para recuperar el control sobre las actividades de su vida diaria que de otro modo no podrían realizar, especialmente en las áreas de comunicación y control de su entorno.En los últimos años, la tecnología está avanzando a grandes pasos y con ella la complejidad de dispositivos ha incrementado significativamente, ampliando el número de posibilidades para controlar sofisticados dispositivos robóticos, prótesis con numerosos grados de libertad o incluso para la aplicación de complejos patrones de estimulación eléctrica en las propias extremidades paralizadas de un usuario, que le permitan ejecutar movimientos precisos. Sin embargo, la cantidad de información que se puede transmitir entre el cerebro y estos dispositivos sigue siendo muy limitada, tanto por el número como por la velocidad a la que se pueden decodificar los comandos neuronales. Por lo tanto, depender únicamente de las señales neuronales no garantiza un control óptimo y preciso.Para poder sacar el máximo partido de estas tecnologías, el campo de las BMIs adoptó el conocido enfoque de “control-compartido". Esta estrategia de control pretende crear un sistema de cooperación entre el usuario y un dispositivo inteligente, liberando al usuario de las tareas más pesadas requeridas para ejecutar la tarea sin llegar a perder la sensación de estar en control. De esta manera, los usuarios solo necesitan centrar su atención en los comandos de alto nivel (por ejemplo, elegir un elemento específico que agarrar, o elegir el destino final donde moverse) mientras el agente inteligente resuelve problemas de bajo nivel (como planificación de trayectorias, esquivar obstáculos, etc.) que permitan realizar la tarea designada de la manera óptima.En particular, esta tesis gira en torno a una señal neuronal cognitiva de alto nivel originada como la falta de coincidencia entre las expectativas del usuario y las acciones reales ejecutadas por los dispositivos inteligentes. Estas señales, denominadas potenciales de error (ErrPs), se consideran una forma natural de intercomunicar nuestro cerebro con máquinas y, por lo tanto, los usuarios solo requieren monitorizar las acciones de un dispositivo y evaluar mentalmente si este último se comporta correctamente o no. Esto puede verse como una forma de supervisar el comportamiento del dispositivo, en el que la decodificación de estas evaluaciones mentales se utiliza para proporcionar a estos dispositivos retroalimentación directamente relacionada con la ejecución de una tarea determinada para que puedan aprender y adaptarse a las preferencias del usuario.Dado que la respuesta neuronal de ErrP está asociada a un evento exógeno (dispositivo que comete una acción errónea), la mayoría de los trabajos desarrollados han intentado distinguir si una acción es correcta o errónea mediante la explotación de eventos discretos en escenarios bien controlados. Esta tesis presenta el primer intento de cambiar hacia configuraciones asíncronas que se centran en tareas relacionadas con el aumento de las capacidades motoras, con el objetivo de desarrollar interfaces para usuarios con movilidad limitada. En este tipo de configuraciones, dos desafíos importantes son que los eventos correctos o erróneos no están claramente definidos y los usuarios tienen que evaluar continuamente la tarea ejecutada, mientras que la clasificación de las señales EEG debe realizarse de forma asíncrona. Como resultado, los decodificadores tienen que lidiar constantemente con la actividad EEG de fondo, que típicamente conduce a una gran cantidad de errores de detección de firmas de error. Para superar estos desafíos, esta tesis aborda dos líneas principales de trabajo.Primero, explora la neurofisiología de las señales neuronales evocadas asociadas con la percepción de errores durante el uso interactivo de un BMI en escenarios continuos y más realistas.Se realizaron dos estudios para encontrar características alternativas basadas en el dominio de la frecuencia como una forma de lidiar con la alta variabilidad de las señales del EEG. Resultados, revelaron que existe un patrón estable representado como oscilaciones "theta" que mejoran la generalización durante la clasificación. Además, se utilizaron técnicas de aprendizaje automático de última generación para aplicar el aprendizaje de transferencia para discriminar asincrónicamente los errores cuando se introdujeron de forma gradual y no se conoce presumiblemente el inicio que desencadena los ErrPs. Además, los análisis de neurofisiología arrojan algo de luz sobre los mecanismos cognitivos subyacentes que provocan ErrP durante las tareas continuas, lo que sugiere la existencia de modelos neuronales en nuestro cerebro que acumulan evidencia y solo toman una decisión al alcanzar un cierto umbral. En segundo lugar, esta tesis evalúa la implementación de estos potenciales relacionados con errores en tres aplicaciones orientadas al usuario. Estos estudios no solo exploran cómo maximizar el rendimiento de decodificación de las firmas ErrP, sino que también investigan los mecanismos neuronales subyacentes y cómo los diferentes factores afectan las señales provocadas.La primera aplicación de esta tesis presenta una nueva forma de guiar a un robot móvil que se mueve en un entorno continuo utilizando solo potenciales de error como retroalimentación que podrían usarse para el control directo de dispositivos de asistencia. Con este propósito, proponemos un algoritmo basado en el emparejamiento de políticas para el aprendizaje de refuerzo inverso para inferir el objetivo del usuario a partir de señales cerebrales.La segunda aplicación presentada en esta tesis contempla los primeros pasos hacia un BCI híbrido para ejecutar distintos tipos de agarre de objetos, con el objetivo de ayudar a las personas que han perdido la funcionalidad motora de su extremidad superior. Este BMI combina la decodificación del tipo de agarre a partir de señales de EEG obtenidas del espectro de baja frecuencia con los potenciales de error provocados como resultado de la monitorización de movimientos de agarre erróneos. Los resultados muestran que, en efecto los ErrP aparecen en combinaciones de señales motoras originadas a partir de movimientos de agarre consistentes en una única repetición. Además, la evaluación de los diferentes factores involucrados en el diseño de la interfaz híbrida (como la velocidad de los estímulos, el tipo de agarre o la tarea mental) muestra cómo dichos factores afectan la morfología del subsiguiente potencial de error evocado.La tercera aplicación investiga los correlatos neuronales y los procesos cognitivos subyacentes asociados con desajustes somatosensoriales producidos por perturbaciones inesperadas durante la estimulación eléctrica neuromuscular en el brazo de un usuario. Este estudio simula los posibles errores que ocurren durante la terapia de neuro-rehabilitación, en la que la activación simultánea de la estimulación aferente mientras los sujetos se concentran en la realización de una tarea motora es crucial para una recuperación óptima. Los resultados muestran que los errores pueden aumentar la atención del sujeto en la tarea y desencadenar mecanismos de aprendizaje que al mismo tiempo podrían promover la neuroplasticidad motora.En resumen, a lo largo de esta tesis, se han diseñado varios paradigmas experimentales para mejorar la comprensión de cómo se generan los potenciales relacionados con errores durante el uso interactivo de BMI en aplicaciones orientadas al usuario. Se han propuesto diferentes métodos para pasar de la configuración bloqueada en el tiempo a la asíncrona, tanto en términos de decodificación como de percepción de los eventos erróneos; y ha explorado tres aplicaciones relacionadas con el aumento de las capacidades motoras, en las cuales los ErrPs se pueden usar para el control de dispositivos, la sustitución de motores y la neuro-rehabilitación.Brain-machine interfaces (BMIs) allow the decoding of cortical activation patterns from the users brain to provide people with severely limited mobility, due to an accident or disease, a way to establish a direct connection between their brain and a device. In this sense, BMIs based in noninvasive recordings, such as the electroencephalogram (EEG) have o↵ered these users new opportunities to regain control over activities of their daily life that they could not perform otherwise, especially in the areas of communication and control of their environment. Over the past years and with the latest technological advancements, devices have significantly grown on complexity expanding the number of possibilities to control complex robotic devices, prosthesis with numerous degrees of freedom or even to apply compound patterns of electrical stimulation on the subjects own paralyzed extremities to execute precise movements. However, the band-with of communication between brain and devices is still very limited, both in terms of the number and the speed at which neural commands can be decoded, and thus solely relying on neural signals do not guarantee accurate control them. In order to benefit of these technologies, the field of BMIs adopted the well-known approach of shared-control. This strategy intends to create a cooperation system between the user and an intelligent device, liberating the user from the burdensome parts of the task without losing the feeling of being in control. Here, users only need to focus their attention on high-level commands (e.g. choose the final destination to reach, or a specific item to grab) while the intelligent agent resolve low-level problems (e.g. trajectory planning, obstacle avoidance, etc) to perform the designated task in the optimal way. In particular, this thesis revolves around a high-level cognitive neural signal originated as the mismatch between the expectations of the user and the actual actions executed by the intelligent devices. These signals, denoted as error-related potentials (ErrPs), are thought as a natural way to intercommunicate our brain with machines and thus users only require to monitor the actions of a device and mentally assess whether the latter is behaving correctly or not. This can be seen as a way to supervise the device’s behavior, in which the decoding of these mental assessments is used to provide these devices with feedback directly related with the performance of a given task so they can learn and adapt to the user’s preferences. Since the ErrP’s neural response is associated to an exogenous event (device committing an erroneous action), most of the developed works have attempted to distinguish whether an action is correct or erroneous by exploiting discrete events under well-controlled scenarios. This thesis presents the first attempt to shift towards asynchronous settings that focus on tasks related with the augmentation of motor capabilities, with the objective of developing interfaces for users with limited mobility. In this type of setups, two important challenges are that correct or erroneous events are not clearly defined and users have to continuously evaluate the executed task, while classification of EEG signals has to be performed asynchronously. As a result, the decoders have to constantly deal with background EEG activity, which typically leads to a large number of missdetection of error signatures. To overcome these challenges, this thesis addresses two main lines of work. First, it explores the neurophysiology of the evoked neural signatures associated with the perception of errors during the interactive use of a BMI in continuous and more realistic scenarios. Two studies were performed to find alternative features based on the frequency domain as a way of dealing with the high variability of EEG signals. Results, revealed that there exists a stable pattern represented as theta oscillations that enhance generalization during classification. Also, state-of-the-art machine learning techniques were used to apply transfer learning to asynchronously discriminate errors when they were introduced in a gradual fashion and the onset that triggers the ErrPs is not presumably known. Furthermore, neurophsysiology analyses shed some light about the underlying cognitive mechanisms that elicit ErrP during continuous tasks, suggesting the existence of neural models in our brain that accumulate evidence and only take a decision upon reaching a certain threshold. Secondly, this thesis evaluates the implementation of these error-related potentials in three user-oriented applications. These studies not only explore how to maximize the decoding performance of ErrP signatures but also investigate the underlying neural mechanisms and how di↵erent factors a↵ect the elicited signals. The first application of this thesis presents a new way to guide a mobile robot moving in a continuous environment using only error potentials as feedback which could be used for the direct control of assistive devices. With this purpose, we propose an algorithm based on policy matching for inverse reinforcement learning to infer the user goal from brain signals. The second application presented in this thesis contemplates the first steps towards a hybrid BMI for grasping oriented to assist people who have lost motor functionality of their upper-limb. This BMI combines the decoding of the type of grasp from low-frequency EEG signals with error-related potentials elicited as the result of monitoring an erroneous grasping. The results show that ErrPs are elicited in combination of motor signatures from the low-frequency spectrum originated from single repetition grasping tasks and evaluates how di↵erent design factors (such as the speed of the stimuli, type of grasp or mental task) impact the morphology of the subsequent evoked ErrP. The third application investigates the neural correlates and the underlying cognitive processes associated with somatosensory mismatches produced by unexpected disturbances during neuromsucular electrical stimulation on a user’s arm. This study simulates possible errors that occur during neurorehabilitation therapy, in which the simultaneous activation of a↵erent stimulation while the subjects are concentrated in performing a motor task is crucial for optimal recovery. The results showed that errors may increase subject’s attention on the task and trigger learning mechanisms that at the same time could promote motor neuroplasticity. In summary, throughout this thesis, several experimental paradigms have been designed to improve the understanding of how error-related potentials are generated during the interactive use of BMIs in user-oriented applications. Di↵erent methods have been proposed to shift from time-locked to asynchronous settings, both in terms of decoding and perception of the erroneous events; and it has explored three applications related with the augmentation of motor capabilities, in which ErrPs can be used for control of devices, motor substitution and neurorehabilitation.<br /

Temporal dynamics of the sensorimotor convergence underlying voluntary limb movement

運動指令信号と感覚信号が統合されて運動が作り出される過程を発見 --中枢神経系と末梢神経系の大規模神経活動記録から明らかに--. 京都大学プレスリリース. 2022-11-24.Descending motor drive and somatosensory feedback play important roles in modulating muscle activity. Numerous studies have characterized the organization of neuronal connectivity in which descending motor pathways and somatosensory afferents converge on spinal motor neurons as a final common pathway. However, how inputs from these two pathways are integrated into spinal motor neurons to generate muscle activity during actual motor behavior is unknown. Here, we simultaneously recorded activity in the motor cortices (MCx), somatosensory afferent neurons, and forelimb muscles in monkeys performing reaching and grasping movements. We constructed a linear model to explain the instantaneous muscle activity using the activity of MCx (descending input) and peripheral afferents (afferent input). Decomposition of the reconstructed muscle activity into each subcomponent indicated that muscle activity before movement onset could first be explained by descending input from mainly the primary motor cortex and muscle activity after movement onset by both descending and afferent inputs. Descending input had a facilitative effect on all muscles, whereas afferent input had a facilitative or suppressive effect on each muscle. Such antagonistic effects of afferent input can be explained by reciprocal effects of the spinal reflex. These results suggest that descending input contributes to the initiation of limb movement, and this initial movement subsequently affects muscle activity via the spinal reflex in conjunction with the continuous descending input. Thus, spinal motor neurons are subjected to temporally organized modulation by direct activation through the descending pathway and the lagged action of the spinal reflex during voluntary limb movement

Cortical Orchestra Conducted by Purpose and Function

학위논문(박사)--서울대학교 대학원 :자연과학대학 협동과정 뇌과학전공,2020. 2. 정천기.촉각과 자기수용감각은 우리의 생존 및 일상생활에 절대적인 영향을 미치는 중요한 감각 기능이다. 말초신경계에서 이 두 가지 기능들에 필요한 정보를 수집하고 전달하는 기계적 수용기 및 그 구심성 신경들에 대한 신호 전달 메커니즘 및 그 특징들은 상대적으로 잘 알려져 있는 편이다. 그러나, 촉각과 자기수용감각을 형성하기 위한 인간 뇌의 피질에서의 정보 처리 메커니즘에 대하여 우리가 현재 알고 있는 바는 극히 일부분이다. 이 논문에서 제시하는 일련의 연구들은 인간 뇌 피질 단계에서 촉각과 자기수용감각의 지각적 처리과정에 대한 거시적 신경계 정보처리 메커니즘을 다룬다. 첫 번째 연구에서는 뇌피질뇌파를 이용하여 인간 일차 및 이차 체성감각 피질에서 인공적인 자극과 일상생활에서 접할 수 있는 자극을 포함하는 다양한 진동촉감각 및 질감 자극에 대한 거시적 신경계 정보처리 특성을 밝혔다. 이 연구에서는 일차 및 이차 체성감각 피질의 촉감각 주파수 특이적인 하이-감마 영역 신경활동이 자극 주파수에 따라 각각 상이한 시간적 다이나믹스를 가지고 변화하는 것을 확인하였다. 또한, 이러한 하이-감마 활동은 성긴 질감과 미세한 입자감을 가진 자연스러운 질감 자극에 대해서도 진동촉감각의 경우와 유사한 패턴을 보였다. 이러한 결과들은 인간의 진동촉감각이 매우 단순한 형태에 자극일지라도 대뇌 체성감각 시스템에 있어 거시적인 다중 영역에서의 계층적 정보처리를 동반한다는 점을 시사한다. 두 번째 연구에서는 인간의 움직임과 관련된 두정엽 영역에서의 하이-감마 뇌활성이 자기수용감각과 같은 말초신경계로부터의 체성감각 피드백을 주로 반영하는지, 아니면 움직임 준비 및 제어를 위한 피질 간 신경 프로세스에 대한 활동을 반영하는지를 조사하였다. 연구 결과, 자발적 운동 중 대뇌 운동감각령에서의 하이-감마 활동은 일차 체성감각피질이 일차 운동피질보다 더 지배적인 것으로 나타났다. 또한 이 연구에서는, 움직임과 관련된 일차 체성감각피질에서의 하이-감마 뇌활동은 말초신경계로부터의 자기수용감각과 촉각에 대한 신경계 정보처리를 주로 반영하는 것을 밝혔다. 이러한 연구들을 바탕으로, 마지막 연구에서는 인간 대뇌에서의 체성감각 지각 프로세스에 대한 거시적 피질 간 네트워크를 규명하고자 하였다. 이를 위해, 51명의 뇌전증 환자에게서 체성감각을 유발했던 뇌피질전기자극 데이터와 46명의 환자에게서 촉감각 자극 및 운동 수행 중에 측정한 뇌피질뇌파 하이-감마 매핑 데이터를 종합적으로 분석하였다. 그 결과, 체성감각 지각 프로세스는 대뇌에서 넓은 영역에 걸쳐 분포하는 체성감각 관련 네트워크의 신경 활성을 수반한다는 것을 알아냈다. 또한, 뇌피질전기자극을 통한 대뇌 지도와 하이-감마 매핑을 통한 대뇌 지도는 서로 상당한 유사성을 보였다. 흥미롭게도, 뇌피질전기자극과 하이-감마 활동을 종합한 뇌지도들로부터 체성감각 관련 뇌 영역의 공간적 분포가 체성감각 기능에 따라 서로 달랐고, 그에 해당하는 각 영역들은 서로 뚜렷하게 다른 시간적 다이나믹스를 가지고 순차적으로 활성화되었다. 이러한 결과들은 체성감각에 대한 거시적 신경계 프로세스가 그 지각적 기능에 따라 뚜렷이 다른 계층적 네트워크를 가진다는 점을 시사한다. 더 나아가, 본 연구에서의 결과들은 체성감각 시스템의 지각-행동 관련 신경활동 흐름에 관한 이론적인 가설에 대하여 설득력 있는 증거를 제시하고 있다.Tactile and proprioceptive perceptions are crucial for our daily life as well as survival. At the peripheral level, the transduction mechanisms and characteristics of mechanoreceptive afferents containing information required for these functions, have been well identified. However, our knowledge about the cortical processing mechanism for them in human is limited. The present series of studies addressed the macroscopic neural mechanism for perceptual processing of tactile and proprioceptive perception in human cortex. In the first study, I investigated the macroscopic neural characteristics for various vibrotactile and texture stimuli including artificial and naturalistic ones in human primary and secondary somatosensory cortices (S1 and S2, respectively) using electrocorticography (ECoG). I found robust tactile frequency-specific high-gamma (HG, 50–140 Hz) activities in both S1 and S2 with different temporal dynamics depending on the stimulus frequency. Furthermore, similar HG patterns of S1 and S2 were found in naturalistic stimulus conditions such as coarse/fine textures. These results suggest that human vibrotactile sensation involves macroscopic multi-regional hierarchical processing in the somatosensory system, even during the simplified stimulation. In the second study, I tested whether the movement-related HG activities in parietal region mainly represent somatosensory feedback such as proprioception from periphery or primarily indicate cortico-cortical neural processing for movement preparation and control. I found that sensorimotor HG activities are more dominant in S1 than in M1 during voluntary movement. Furthermore, the results showed that movement-related HG activities in S1 mainly represent proprioceptive and tactile feedback from periphery. Given the results of previous two studies, the final study aimed to identify the large-scale cortical networks for perceptual processing in human. To do this, I combined direct cortical stimulation (DCS) data for eliciting somatosensation and ECoG HG band (50 to 150 Hz) mapping data during tactile stimulation and movement tasks, from 51 (for DCS mapping) and 46 patients (for HG mapping) with intractable epilepsy. The results showed that somatosensory perceptual processing involves neural activation of widespread somatosensory-related network in the cortex. In addition, the spatial distributions of DCS and HG functional maps showed considerable similarity in spatial distribution between high-gamma and DCS functional maps. Interestingly, the DCS-HG combined maps showed distinct spatial distributions depending on the somatosensory functions, and each area was sequentially activated with distinct temporal dynamics. These results suggest that macroscopic neural processing for somatosensation has distinct hierarchical networks depending on the perceptual functions. In addition, the results of the present study provide evidence for the perception and action related neural streams of somatosensory system. Throughout this series of studies, I suggest that macroscopic somatosensory network and structures of our brain are intrinsically organized by perceptual function and its purpose, not by somatosensory modality or submodality itself. Just as there is a purpose for human behavior, so is our brain.PART I. INTRODUCTION 1 CHAPTER 1: Somatosensory System 1 1.1. Mechanoreceptors in the Periphery 2 1.2. Somatosensory Afferent Pathways 4 1.3. Cortico-cortical Connections among Somatosensory-related Areas 7 1.4. Somatosensory-related Cortical Regions 8 CHAPTER 2: Electrocorticography 14 2.1. Intracranial Electroencephalography 14 2.2. High-Gamma Band Activity 18 CHAPTER 3: Purpose of This Study 24 PART II. EXPERIMENTAL STUDY 26 CHAPTER 4: Apparatus Design 26 4.1. Piezoelectric Vibrotactile Stimulator 26 4.2. Magnetic Vibrotactile Stimulator 29 4.3. Disc-type Texture Stimulator 33 4.4. Drum-type Texture Stimulator 36 CHAPTER 5: Vibrotactile and Texture Study 41 5.1. Introduction 42 5.2. Materials and Methods 46 5.2.1. Patients 46 5.2.2. Apparatus 47 5.2.3. Experimental Design 49 5.2.4. Data Acquisition and Preprocessing 50 5.2.5. Analysis 51 5.3. Results 54 5.3.1. Frequency-specific S1/S2 HG Activities 54 5.3.2. S1 HG Attenuation during Flutter and Vibration 62 5.3.3. Single-trial Vibration Frequency Classification 64 5.3.4. S1/S2 HG Activities during Texture Stimuli 65 5.4. Discussion 69 5.4.1. Comparison with Previous Findings 69 5.4.2. Tactile Frequency-dependent Neural Adaptation 70 5.4.3. Serial vs. Parallel Processing between S1 and S2 72 5.4.4. Conclusion of Chapter 5 73 CHAPTER 6: Somatosensory Feedback during Movement 74 6.1. Introduction 75 6.2. Materials and Methods 79 6.2.1. Subjects 79 6.2.2. Tasks 80 6.2.3. Data Acquisition and Preprocessing 82 6.2.4. S1-M1 HG Power Difference 85 6.2.5. Classification 86 6.2.6. Timing of S1 HG Activity 86 6.2.7. Correlation between HG and EMG signals 87 6.3. Results 89 6.3.1. HG Activities Are More Dominant in S1 than in M1 89 6.3.2. HG Activities in S1 Mainly Represent Somatosensory Feedback 94 6.4. Discussion 100 6.4.1. S1 HG Activity Mainly Represents Somatosensory Feedback 100 6.4.2. Further Discussion and Future Direction in BMI 102 6.4.3. Conclusion of Chapter 6 103 CHAPTER 7: Cortical Maps of Somatosensory Function 104 7.1. Introduction 106 7.2. Materials and Methods 110 7.2.1. Participants 110 7.2.2. Direct Cortical Stimulation 114 7.2.3. Classification of Verbal Feedbacks 115 7.2.4. Localization of Electrodes 115 7.2.5. Apparatus 116 7.2.6. Tasks 117 7.2.7. Data Recording and Processing 119 7.2.8. Mapping on the Brain 120 7.2.9. ROI-based Analysis 122 7.3. Results 123 7.3.1. DCS Mapping 123 7.3.2. Three and Four-dimensional HG Mapping 131 7.3.3. Neural Characteristics among Somatosensory-related Areas 144 7.4. Discussion 146 7.4.1. DCS on the Non-Primary Areas 146 7.4.2. Two Streams of Somatosensory System 148 7.4.3. Functional Role of ventral PM 151 7.4.4. Limitation and Perspective 152 7.4.5. Conclusion of Chapter 7 155 PART III. CONCLUSION 156 CHAPTER 8: Conclusion and Perspective 156 8.1. Perspective and Future Work 157 References 160 Abstract in Korean 173Docto