Temperatures achieved in human and canine neocortex during intraoperative passive or active focal cooling

Focal cortical cooling inhibits seizures and prevents acquired epileptogenesis in rodents. To investigate the potential clinical utility of this treatment modality, we examined the thermal characteristics of canine and human brain undergoing active and passive surface cooling in intraoperative settings. Four patients with intractable epilepsy were treated in a standard manner. Before the resection of a neocortical epileptogenic focus, multiple intraoperative studies of active (custom-made cooled irrigation-perfused grid) and passive (stainless steel probe) cooling were performed. We also actively cooled the neocortices of two dogs with perfused grids implanted for 2 hours. Focal surface cooling of the human brain causes predictable depth-dependent cooling of the underlying brain tissue. Cooling of 0.6–2°C was achieved both actively and passively to a depth of 10–15 mm from the cortical surface. The perfused grid permitted comparable and persistent cooling of canine neocortex when the craniotomy was closed. Thus, the human cortex can easily be cooled with the use of simple devices such as a cooling grid or a small passive probe. These techniques provide pilot data for the design of a permanently implantable device to control intractable epilepsy

Getting the best outcomes from epilepsy surgery.

Neurosurgery is an underutilized treatment that can potentially cure drug-refractory epilepsy. Careful, multidisciplinary presurgical evaluation is vital for selecting patients and to ensure optimal outcomes. Advances in neuroimaging have improved diagnosis and guided surgical intervention. Invasive electroencephalography allows the evaluation of complex patients who would otherwise not be candidates for neurosurgery. We review the current state of the assessment and selection of patients and consider established and novel surgical procedures and associated outcome data. We aim to dispel myths that may inhibit physicians from referring and patients from considering neurosurgical intervention for drug-refractory focal epilepsies. Ann Neurol 2018;83:676-690

Miniaturized wireless electronic device for application on rodents thermal neuromodulation

Dissertação de mestrado em Biomedical Engineering, Medical Electronics BranchA epilepsia é uma doença neurológica que afeta muitas pessoas em todo o mundo, e cerca de 30% dos pacientes epiléticos são resistentes aos medicamentos. Normalmente, estes são obrigados a ficar em casa, uma vez que a opção é uma cirurgia de ressecção focal, o que nem sempre é possível ou aceite. Portanto, e como em muitas patologias onde é possível o desenvolvimento de dispositivos médicos capazes de melhorar a qualidade de vida dos pacientes, a tecnologia pode-se associar à medicina e fornecer uma solução alternativa para tais pacientes. Dos vários estudos já realizados neste campo, a neuromodulação térmica é uma técnica promissora, uma vez que reduz ou possivelmente interrompe as crises epiléticas. Assim, a fim de potencializar uma solução futura para estes pacientes, é necessário primeiro realizar vários testes experimentais com modelos animais. Com o intuito de melhor compreender o funcionamento dos testes in vivo, foram realizados testes em GAERS no Grenoble Institute of Neuroscience com um dispositivo previamente desenvolvido, a fim de recolher dados sobre o efeito de arrefecimento nos neurónios. Isso permitiu alargar o conhecimento sobre o arrefecimento focal, mas também permitiu encontrar limitações no dispositivo utilizado, dado que era necessário que este estivesse conectado por fios para ser possível aplicar frio e gravar o EEG. Assim, o objetivo desta dissertação foi melhorar a comunicação sem fios de um dispositivo eletrónico capaz de controlar um Peltier e registar a atividade elétrica cerebral de um roedor. O sistema possui dois módulos, um que maioritariamente transmite dados e outro que os recebe. Nesse sentido, o transmissor possui toda a eletrónica associada à comunicação sem fios, à aquisição de sinais eletrofisiológicos e ao controlo do Peltier. Já o recetor possui a eletrónica para a comunicação sem fios e um conector USB para se conectar ao computador. Com o intuito de aumentar o débito binário da transação de dados, os dois módulos foram programados com o protocolo proprietário da Nordic Semiconductor, denominado Enhanced ShockBurst que opera na banda 2.4 GHz. Após a implementação do software, obteve-se um débito binário de 368640 bps, o que é 17 vezes superior ao protocolo usado anteriormente. Assim, é possível adquirir biossinais com frequências mais elevadas, ou então, com frequências mais baixas, mas com mais resolução e, ainda a visualização de mais do que um canal. De forma a validar todo o sistema, realizaram-se vários testes. Um dos testes foi colocar nos elétrodos uma onda sinusoidal e observar no computador se a onda recebida era igual à onda de entrada. O outro foi determinar a taxa de erros associada à comunicação e o tempo de vida da bateria.Epilepsy is a neurological disorder that affects numerous people worldwide, and around 30% of epileptic patients are drug resistant. Usually, they are restrained at home, since the option is a focal resection surgery, which is not always possible or accepted. Therefore, and as in many pathologies, where it allows the development of medical devices capable of improving patients’ quality of life, technology may be used here to help medicine providing an alternative solution for such patients. Of the many studies already conducted in this field, thermal neuromodulation is a promising technique as it reduces or possibly interrupts epileptic seizures. Thus, in order to leverage a future solution for these patients, it’s first necessary to run several experimental tests with animal models. To better understand how in vivo tests work, tests were initially performed on GAERS at the Grenoble Institute of Neuroscience with a previously developed device in order to collect data on the cooling effect on neurons. This allowed to extend the knowledge about focal cooling, but also allowed to find limitations in the device used, as it was required to be wired in order to be able to apply cold and record the EEG. Therefore, the aim of this dissertation was to improve the wireless communication of an electronic device capable of controlling a Peltier module and recording the electrical brain activity of a rodent. The system has two modules, one that mostly transmits data and another that receives them. In this sense, the transmitter has all the electronics associated with wireless communication, electrophysiological signal acquisition, and Peltier control. The receiver, on the other hand, has the electronics for wireless communication and a USB connector to connect to the computer. In order to increase the binary throughput of the data transaction, the two modules were programmed with the 2.4 GHz proprietary protocol from Nordic Semiconductor, called Enhanced ShockBurst. After implementation of the software, a binary throughput of 368640 bps was obtained, which is 17 times higher than the previously used protocol. Thus, it is possible to acquire biosignals at higher frequencies, or at lower frequencies but with more resolution, and to visualize more than one channel. In order to validate the whole system, several tests were performed. One of the tests was to place a sine wave on the electrodes and observe in the computer if the signal received was equal to the input wave. The other, on the other hand, was to determine the error rate associated with communication and battery life

On mapping epilepsy : magneto- and electroencephalographic characterizations of epileptic activities

Epilepsy is one of the most common neurological disorder, affecting up to 10 individuals per 1000 persons. The disorder have been known for several thousand years, with the first clinical descriptions dating back to ancient times. Nonetheless, characterization of the dynamics underlying epilepsy remains largely unknown. Understanding these patophysiological processes requires unifying both a neurobiological perspective, as well as a technically advanced neuroimaging perspective. The incomplete insight into epilepsy dynamics is reflected by the insufficient treatment options. Approximately 30% of all patients do not respond to anti-epileptic drugs (AEDs) and thus suffers from recurrent seizures despite adequate pharmacological treatments. These pharmacoresistant patients often undergo epilepsy surgery evaluations. Epilepsy surgery aims to resect the part of the brain that generates the epileptic seizure activity (seizure onset zone, SOZ). Nonetheless, up to 50% of all patients relapse after surgery. This can be due to incomplete mapping of both the SOZ and of other structures that might be involved in seizure initiation and propagation. Such cortical and subcortical structures are collectively referred to as the epileptic network. Historically, epilepsy was considered to be either a generalized disorder involving the entire brain, or a highly localized, focal, disorder. The modern technological development of both structural and functional neuroimaging has drastically altered this view. This development has made significant contributions to the now prevailing view that both generalized and focal epilepsies arise from more or less widespread pathological network pathways. Visualization of these pathways play an important role in the presurgical planning. Thus, both improved characterization and understanding of such pathways are pivotal in improvement of epilepsy diagnostics and treatments. It is evident that epilepsy research needs to stand on two legs: Both improved understanding of pathological, neurobiological and neurophysiological process, and improved neuroimaging instrumentation. Epilepsy research do not only span from visualization to understanding of neurophysiological processes, but also from cellular, neuronal, microscopic processes, to dynamical, large-scale network processes. It is well known that neurons involved in epileptic activities exhibit specific, pathological firing patterns. Genetic mutations resulting in neuronal ion channel defects can cause severe, and even lethal, epileptic syndromes in children, clearly illustrating a role for neuron membrane properties in epilepsy. However, cellular processes themselves cannot explain how epileptic seizures can involve, and propagate across, large cortical areas and generate seizure-specific symptomatologies. A strict cellular perspective can neither explain epilepsy-associated pathological interactions between larger distant regions in between seizures. Instead, the dynamical effects of cellular synchronization across both mesoscopic and macroscopic scales also need to be considered. Today, the only means to study such effects in human subjects are by combinations of neuroimaging modalities. However, as all measurement techniques, these exhibit individual limitations that affect the kind of information that can be inferred from these. Thus, once more we reach the conclusion that epilepsy research needs to rest upon both a neurophysiological/neurobiological leg, and a technical/instrumentational leg. In accordance with this necessity of a dual approach to epilepsy, this thesis covers both neurophysiological aspects of epileptic activity development, as well as functional neuroimaging instrumentation development with focus on epileptic activity detection and localization. Part 1 (neurophysiological part) is concerned with the neurophysiological dynamical changes that underlie development of so called interictal epileptiform discharges (IEDs) with special focus on the role of low-frequency oscillations. To this aim, both conventional magnetoencephalography (MEG) and intracranial electroencephalography (iEEG) with neurostimulation is analyzed. Part 2 (instrumentation part) is concerned with development of cutting-edge, novel on-scalp magnetoencephalography (osMEG) within clinical epilepsy evaluations and research with special focus on IEDs. The theses cover both modeling of osMEG characteristics, as well as the first-ever osMEG recording of a temporal lobe epilepsy patient

Bioresorbable silicon electronics for transient spatiotemporal mapping of electrical activity from the cerebral cortex.

Bioresorbable silicon electronics technology offers unprecedented opportunities to deploy advanced implantable monitoring systems that eliminate risks, cost and discomfort associated with surgical extraction. Applications include postoperative monitoring and transient physiologic recording after percutaneous or minimally invasive placement of vascular, cardiac, orthopaedic, neural or other devices. We present an embodiment of these materials in both passive and actively addressed arrays of bioresorbable silicon electrodes with multiplexing capabilities, which record in vivo electrophysiological signals from the cortical surface and the subgaleal space. The devices detect normal physiologic and epileptiform activity, both in acute and chronic recordings. Comparative studies show sensor performance comparable to standard clinical systems and reduced tissue reactivity relative to conventional clinical electrocorticography (ECoG) electrodes. This technology offers general applicability in neural interfaces, with additional potential utility in treatment of disorders where transient monitoring and modulation of physiologic function, implant integrity and tissue recovery or regeneration are required

Brain Injury

The present two volume book "Brain Injury" is distinctive in its presentation and includes a wealth of updated information on many aspects in the field of brain injury. The Book is devoted to the pathogenesis of brain injury, concepts in cerebral blood flow and metabolism, investigative approaches and monitoring of brain injured, different protective mechanisms and recovery and management approach to these individuals, functional and endocrine aspects of brain injuries, approaches to rehabilitation of brain injured and preventive aspects of traumatic brain injuries. The collective contribution from experts in brain injury research area would be successfully conveyed to the readers and readers will find this book to be a valuable guide to further develop their understanding about brain injury