Deep Brain Stimulation (DBS) Applications

The issue is dedicated to applications of Deep Brain Stimulation and, in this issue, we would like to highlight the new developments that are taking place in the field. These include the application of new technology to existing indications, as well as ‘new’ indications. We would also like to highlight the most recent clinical evidence from international multicentre trials. The issue will include articles relating to movement disorders, pain, psychiatric indications, as well as emerging indications that are not yet accompanied by clinical evidence. We look forward to your expert contribution to this exciting issue

A neuroprothesis for tremor management

Tremor is the most common movement disorder, affecting ∼ 15 % of people over 50 years old according to some estimates. It appears due to a number of syndromes, being essential tremor and Parkinson's disease the most prevalent among them. None of these conditions is fully understood. Tremor is currently treated through drugs or neurosurgery, but unfortunately, it is not managed effectively in ∼25 % of the patients. Therefore, it constitutes a major cause of loss of independence and quality of life. Various alternative approaches for tremor management are reported in the literature. Among them, those devices that rely on the application of forces to the tremulous segments show a considerable potential. A number of prototypes that exploit this principle are available, spanning fixed devices and orthoses. However, none of them has fulfilled user's expectation for continuous use during daily living. This thesis presents the development and validation of a neuroprosthesis for tremor management. A neuroprosthesis is a system that restores or compensates for a neurological function that is lost. In this case, the neuroprosthesis aims at compensating the functional disability caused by the tremor. To this end, it applies forces to the tremulous limb through the control of muscle contraction, which is modulated according to the characteristics of the tremor. The concept design envisions the device as a textile that is worn on the affected limb, thus meeting the usability requirements defined by the patients. The development of the neuroprosthesis comprised the following tasks: 1. The development of a concept design of the neuroprosthesis, which incorporates state of the art knowledge on tremor, and user's needs. 2. The design and validation of a cognitive interface that parameterizes the tremor in functional contexts. This interface provides the information that the neuroprosthesis uses for tremor suppression. Two versions are developed: a multimodal interface that integrates the recordings of the whole neuromusculoskeletal system, and an interface incorporating only wearable movement sensors. The latter is intended for the functional validation of the neuroprosthesis, while the former is a proof of concept of an optimal interface for this type of applications. 3. The development of a novel approach for tremor suppression through transcutaneous neurostimulation. The approach relies on the modulation of muscle cocontraction as a means of attenuating the tremor without the need of conventional actuators. The experimental validation here provided demonstrates the feasibility and interest of the approach. In parallel with the validation of the neuroprosthesis, I performed a detailed study on the physiology of motoneurons in tremor, given the lack of a complete description of its behavior. The outcome of this study contributes to the interpretation of the results obtained with the neuroprosthesis, and opens new research lines, both related to alternative interventions and basic neuroscience. In summary, the results here presented demonstrate that tremor may be accurately parameterized while the patient performs functional activities, and that this information may be exploited to drive a neuroprosthesis for tremor management. Furthermore, the novel approach for tremor suppression presented in this dissertation constitutes a potential approach for treating upper limb tremor, either alone, or as a complement to pharmacotherapy. These results encourage the validation of the neuroprosthesis in a large cohort of patients, in order to enable its translation to the market. -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------El temblor es el trastorno del movimiento más común, afectando, según algunas estimaciones, al ∼15 % de la población de más de 50 años. Existen diversos "síndromes" que causan temblor, siendo el temblor esencial y la enfermedad de Parkinson los que presentan mayor prevalencia. Además, cabe resaltar que no existe una descripción completa de ninguno de ellos. En la actualidad el temblor se trata mediante una serie de fármacos o neurocirugía. A pesar de ello, el ∼ 25 % de los pacientes sufren problemas funcionales debido a su condición. Por tanto, es evidente que el temblor constituye una de las principales causas de dependencia y pérdida de calidad de vida. Realizando una revisión de las publicaciones científicas sobre el temblor, se observa que se ha propuesto un considerable número de tratamientos alternativos. Entre ellos destacan los dispositivos que se fundamentan en la aplicación de fuerzas sobre los segmentos afectados por el temblor, de los que ya se ha evaluado una serie de prototipos. Estos abarcan desde dispositivos fijados a otras estructuras hasta ortesis. Sin embargo, ninguno de ellos satisface las expectativas de los usuarios para su uso durante el día a día. Esta tesis presenta el diseño y validación de una neruoprótesis para el tratamiento del temblor. Una neuroprótesis es un sistema que reemplaza o compensa una función neurológica perdida. En este caso, la neuroprótesis tiene como objetivo compensar la discapacidad motora causada por el temblor. Para ello aplica fuerzas al miembro afectado a través del control del nivel de contracción muscular, que se modula según las características del temblor. El diseño conceptual contempla al dispositivo como un textil que se viste en el brazo afectado, satisfaciendo los requisitos de usabilidad definidos por los pacientes. El desarrollo de la neuroprótesis abarcó las siguientes tareas: 1. El desarrollo del diseño conceptual de la neuroprótesis, que incorpora el conocimiento actual sobre el temblor, y las necesidades de los usuarios. 2. El diseño y validación de una interfaz cognitiva que parametriza el temblor durante tareas funcionales. La información obtenida con esta interfaz es usada por la neuroprótesis para modular la corriente aplicada mediante técnicas de neuroestimulación. Se desarrollan dos versiones de la interfaz cognitiva: una interfaz multimodal que integra información de todo el sistema neuromusculoesquelético, y una interfaz que implementa únicamente sensores vestibles de movimiento. La segunda interfaz fue la que se usó durante la validación funcional de la neuroprótesis, mientras que la primera es una prueba de concepto de una interfaz óptima para este tipo de aplicaciones. 3. El desarrollo de una nueva aproximación para la supresión del temblor mediante neuroestimulación transcutánea. Dicha aproximación se fundamenta en la modulación del grado de co-contracción de los músculos afectados como forma de atenuar el temblor, sin necesidad de usar actuadores convencionales. La evaluación experimental sirvió para demostrar la viabilidad e interés de la intervención. En paralelo a la validación de la neuroprótesis, llevé a cabo un estudio detallado de la fisiología de las motoneuronas en el caso del temblor, dado que no existe una descripción del funcionamiento de las mismas en el caso de este trastorno. Este estudio sirve para ayudar a la interpretación de los resultados de la neuroprótesis, y para abrir una serie de líneas futuras de investigación, tanto sobre nuevas intervenciones para el temblor, como sobre neurociencia básica. En resumen, los resultados que se presentan en esta tesis demuestran que es posible parametrizar de una forma precisa el temblor durante la realización de tareas funcionales, y que esta información sirve para controlar una neuroprótesis para el tratamiento del temblor. Además, la nueva aproximación para la compensación del temblor que se presenta tiene el potencial de convertirse en un tratamiento alternativo para el temblor de miembro superior, ya sea de forma independiente o como complemento a los fármacos. Estos resultados alientan la validación de la neuroprótesis en una cohorte grande de pacientes, con el objetivo de facilitar su transferencia al mercado

A cumulative index to the 1976 issues of a continuing bibliography on Aerospace Medicine and Biology

This publication is a cumulative index to the abstracts contained in Supplements 151 through 162 of Aerospace Medicine and Biology: A continuing bibliography. It includes three indexes - subject, personal author, and corporate source

Diagnosis and Treatment of Parkinson's Disease

Parkinson's disease is diagnosed by history and physical examination and there are no laboratory investigations available to aid the diagnosis of Parkinson's disease. Confirmation of diagnosis of Parkinson's disease thus remains a difficulty. This book brings forth an update of most recent developments made in terms of biomarkers and various imaging techniques with potential use for diagnosing Parkinson's disease. A detailed discussion about the differential diagnosis of Parkinson's disease also follows as Parkinson's disease may be difficult to differentiate from other mimicking conditions at times. As Parkinson's disease affects many systems of human body, a multimodality treatment of this condition is necessary to improve the quality of life of patients. This book provides detailed information on the currently available variety of treatments for Parkinson's disease including pharmacotherapy, physical therapy and surgical treatments of Parkinson's disease. Postoperative care of patients of Parkinson's disease has also been discussed in an organized manner in this text. Clinicians dealing with day to day problems caused by Parkinson's disease as well as other healthcare workers can use beneficial treatment outlines provided in this book

Aerospace medicine and biology: A continuing bibliography with indexes, supplement 130, July 1974

This special bibliography lists 291 reports, articles, and other documents introduced into the NASA scientific and technical information system in June 1974

Models and Analysis of Vocal Emissions for Biomedical Applications

The MAVEBA Workshop proceedings, held on a biannual basis, collect the scientific papers presented both as oral and poster contributions, during the conference. The main subjects are: development of theoretical and mechanical models as an aid to the study of main phonatory dysfunctions, as well as the biomedical engineering methods for the analysis of voice signals and images, as a support to clinical diagnosis and classification of vocal pathologies

Mean-field analysis of basal ganglia and thalamocortical dynamics

When modeling a system as complex as the brain, considerable simplifications are inevitable. The nature of these simplifications depends on the available experimental evidence, and the desired form of model predictions. A focus on the former often inspires models of networks of individual neurons, since properties of single cells are more easily measured than those of entire populations. However, if the goal is to describe the processes responsible for the electroencephalogram (EEG), such models can become unmanageable due to the large numbers of neurons involved. Mean-field models in which assemblies of neurons are represented by their average properties allow activity underlying the EEG to be captured in a tractable manner. The starting point of the results presented here is a recent physiologically-based mean-field model of the corticothalamic system, which includes populations of excitatory and inhibitory cortical neurons, and an excitatory population representing the thalamic relay nuclei, reciprocally connected with the cortex and the inhibitory thalamic reticular nucleus. The average firing rates of these populations depend nonlinearly on their membrane potentials, which are determined by afferent inputs after axonal propagation and dendritic and synaptic delays. It has been found that neuronal activity spreads in an approximately wavelike fashion across the cortex, which is modeled as a two-dimensional surface. On the basis of the literature, the EEG signal is assumed to be roughly proportional to the activity of cortical excitatory neurons, allowing physiological parameters to be extracted by inverse modeling of empirical EEG spectra. One objective of the present work is to characterize the statistical distributions of fitted model parameters in the healthy population. Variability of model parameters within and between individuals is assessed over time scales of minutes to more than a year, and compared with the variability of classical quantitative EEG (qEEG) parameters. These parameters are generally not normally distributed, and transformations toward the normal distribution are often used to facilitate statistical analysis. However, no single optimal transformation exists to render data distributions approximately normal. A uniformly applicable solution that not only yields data following the normal distribution as closely as possible, but also increases test-retest reliability, is described in Chapter 2. Specialized versions of this transformation have been known for some time in the statistical literature, but it has not previously found its way to the empirical sciences. Chapter 3 contains the study of intra-individual and inter-individual variability in model parameters, also providing a comparison of test-retest reliability with that of commonly used EEG spectral measures such as band powers and the frequency of the alpha peak. It is found that the combined model parameters provide a reliable characterization of an individual's EEG spectrum, where some parameters are more informative than others. Classical quantitative EEG measures are found to be somewhat more reproducible than model parameters. However, the latter have the advantage of providing direct connections with the underlying physiology. In addition, model parameters are complementary to classical measures in that they capture more information about spectral structure. Another conclusion from this work was that a few minutes of alert eyes-closed EEG already contain most of the individual variability likely to occur in this state on the scale of years. In Chapter 4, age trends in model parameters are investigated for a large sample of healthy subjects aged 6-86 years. Sex differences in parameter distributions and trends are considered in three age ranges, and related to the relevant literature. We also look at changes in inter-individual variance across age, and find that subjects are in many respects maximally different around adolescence. This study forms the basis for prospective comparisons with age trends in evoked response potentials (ERPs) and alpha peak morphology, besides providing a standard for the assessment of clinical data. It is the first study to report physiologically-based parameters for such a large sample of EEG data. The second main thrust of this work is toward incorporating the thalamocortical system and the basal ganglia in a unified framework. The basal ganglia are a group of gray matter structures reciprocally connected with the thalamus and cortex, both significantly influencing, and influenced by, their activity. Abnormalities in the basal ganglia are associated with various disorders, including schizophrenia, Huntington's disease, and Parkinson's disease. A model of the basal ganglia-thalamocortical system is presented in Chapter 5, and used to investigate changes in average firing rates often measured in parkinsonian patients and animal models of Parkinson's disease. Modeling results support the hypothesis that two pathways through the basal ganglia (the so-called direct and indirect pathways) are differentially affected by the dopamine depletion that is the hallmark of Parkinson's disease. However, alterations in other components of the system are also suggested by matching model predictions to experimental data. The dynamics of the model are explored in detail in Chapter 6. Electrophysiological aspects of Parkinson's disease include frequency reduction of the alpha peak, increased relative power at lower frequencies, and abnormal synchronized fluctuations in firing rates. It is shown that the same parameter variations that reproduce realistic changes in mean firing rates can also account for EEG frequency reduction by increasing the strength of the indirect pathway, which exerts an inhibitory effect on the cortex. Furthermore, even more strongly connected subcircuits in the indirect pathway can sustain limit cycle oscillations around 5 Hz, in accord with oscillations at this frequency often observed in tremulous patients. Additionally, oscillations around 20 Hz that are normally present in corticothalamic circuits can spread to the basal ganglia when both corticothalamic and indirect circuits have large gains. The model also accounts for changes in the responsiveness of the components of the basal ganglia-thalamocortical system, and increased synchronization upon dopamine depletion, which plausibly reflect the loss of specificity of neuronal signaling pathways in the parkinsonian basal ganglia. Thus, a parsimonious explanation is provided for many electrophysiological correlates of Parkinson's disease using a single set of parameter changes with respect to the healthy state. Overall, we conclude that mean-field models of brain electrophysiology possess a versatility that allows them to be usefully applied in a variety of scenarios. Such models allow information about underlying physiology to be extracted from the experimental EEG, complementing traditional measures that may be more statistically robust but do not provide a direct link with physiology. Furthermore, there is ample opportunity for future developments, extending the basic model to encompass different neuronal systems, connections, and mechanisms. The basal ganglia are an important addition, not only leading to unified explanations for many hitherto disparate phenomena, but also contributing to the validation of this form of modeling

Cellular And Molecular Insight Into Autonomic Function And Dysfunction

The autonomic nervous system (ANS) controls several vital functions of the body, especially the autonomic regulation of respiratory and cardiovascular systems. Dysfunction of either can be life-threatening. Some of cellular and molecular mechanisms underlying the respiratory and cardiovascular dysfunction is more critical and general. The demonstration of such general processes not only may help the understanding of etiology and pathophysiology of the diseases, but also suggests potential therapeutic modalities for the diseases. Severe breathing disorders including high apnea rate and breathing irregularity are found in Rett syndrome (RTT). In a novel rat model of RTT, we compared rat physical condition and behaviors with traditional mouse models of RTT. We found that the novel Mecp2−/Y rat model as an alternative RTT model recapitulated numerous RTT-like symptoms. To uncover the neuronal mechanisms underlying the RTT respiratory disorders, we performed in vivo recording from brainstem neurons in ventral respiratory column (VRC). Excessive activity of both inspiratory and expiratory neurons as well as ectopic discharge of phrenic nerve were detected in null rats. Such defects were likely caused by hyperexcitability of respiratory neurons due to inadequate synaptic inhibition necessary for phase switching. Then we took the GABAergic intervention to hyperexcitability of respiratory neurons, and successfully corrected the defects in neuronal firing patterns as well as the RTT breathing phenotypes. Similarly, change of cellular excitability was also observed in diabetic vascular complications. A critical player for the membrane excitability of vascular smooth muscle cells (VSMCs) is the KATP channel that is strongly suppressed by methylglyoxal (MGO) known to be overly produced with persistent hyperglycemia. The elevated level of microRNA (miR)-9a-3p contributed to the down-regulation of vascular KATP channels. miR-9a-3p inhibition using antisense oligonuecleotides corrected the dysfunction of KATP channels. Since VSMC membrane excitability plays an important role in vascular tone regulation, we generated a new strain of transgenic Tagln-ChR mouse model and demonstrate an alterative to manipulate VSMC membrane excitability and vascular tone using optogenetic approaches. Thus several molecular targets in cardiorespiratory system have been demonstrated underlying membrane excitability and the developments of several disease conditions in this thesis study

VISUALIZATION OF ULTRASOUND INDUCED CAVITATION BUBBLES USING SYNCHROTRON ANALYZER BASED IMAGING

Ultrasound is recognized as the fastest growing medical modality for imaging and therapy. Being noninvasive, painless, portable, X-ray radiation-free and far less expensive than magnetic resonance imaging, ultrasound is widely used in medicine today. Despite these benefits, undesirable bioeffects of high-frequency sound waves have raised concerns; particularly, because ultrasound imaging has become an integral part of prenatal care today and is increasingly used for therapeutic applications. As such, ultrasound bioeffects must be carefully considered to ensure optimal benefits-to-risk ratio. In this context, few studies have been done to explore the physics (i.e. ‘cavitation’) behind the risk factors. One reason may be associated with the challenges in visualization of ultrasound-induced cavitation bubbles in situ. To address this issue, this research aims to develop a synchrotron-based assessment technique to enable visualization and characterization of ultrasound-induced microbubbles in a physiologically relevant medium under standard ultrasound operating conditions. The first objective is to identify a suitable synchrotron X-ray imaging technique for visualization of ultrasound-induced microbubbles in water. Two synchrotron X-ray phase-sensitive imaging techniques, in-line phase contrast imaging (PCI) and analyzer-based imaging (ABI), were evaluated. Results revealed the superiority of the ABI method compared to PCI for visualization of ultrasound-induced microbubbles. The second main objective is to employ the ABI method to assess the effects of ultrasound acoustic frequency and power on visualization and mapping of ultrasound-induced microbubble patterns in water. The time-averaged probability of ultrasound-induced microbubble occurrence along the ultrasound beam propagation in water was determined using the ABI method. Results showed the utility of synchrotron ABI for visualizing cavitation bubbles formed in water by clinical ultrasound systems working at high frequency and output powers as low as used for therapeutic systems. It was demonstrated that the X-ray ABI method has great potential for mapping ultrasound-induced microbubble patterns in a fluidic environment under different ultrasound operating conditions of clinical therapeutic devices. Taken together, this research represents an advance in detection techniques for visualization and mapping of ultrasound-induced microbubble patterns using the synchrotron X-ray ABI method without usage of contrast agents. Findings from this research will pave the road toward the development of a synchrotron-based detection technique for characterization of ultrasound-induced cavitation microbubbles in soft tissues in the future