Caracterización beta, gamma y de oscilaciones de alta frecuencia para localización de diana en procedimientos de Estimulación Cerebral Profunda

Deep Brain Stimulation (DBS) has been successfully used to treat patients with Parkinson’s Disease. DBS employs an electrode that regulates the oscillatory activity of the basal ganglia, such as the subthalamic nucleus (STN). A critical point during the surgical implantation of such electrode is the precise localization of the target. This is done using presurgical images, stereotactic frames, and microelectrode recordings (MER). The latter allows neurophysiologists to visualize the electrical activity of different structures along the surgical track, each of them with well-defined variations in the frequency pattern; however, this is far from an automatic or semi-automatic method to help these specialists make decisions concerning the surgical target. To pave the way to automation, we analyzed three frequency bands in MER signals acquired from 11 patients undergoing DBS: beta (13-40 Hz), gamma (40-200 Hz), and high-frequency oscillations (HFO – 201-400 Hz). In this study, we propose and assess five indexes in order to detect the STN: variations in autoregressive parameters and their derivative along the surgical track, the energy of each band calculated using the Yule-Walker power spectral density, the high-to-low (H/L) ratio, and its derivative. We found that the derivative of one parameter of the beta band and the H/L ratio of the HFO/gamma bands produced errors in STN targeting like those reported in the literature produced by image-based methods (<2 mm). Although the indexes introduced here are simple to compute and could be applied in real time, further studies must be conducted to be able to generalize their results.La estimulación cerebral profunda (DBS por sus siglas en inglés) ha sido usada exitosamente en el tratamiento de pacientes con enfermedad de Párkinson. La DBS tiene un electrodo que regula la actividad oscilatoria de los ganglios basales involucrados, como el núcleo subtalámico (STN). Un aspecto crítico en el implante de dicho electrodo es la localización precisa de la diana quirúrgica. Esta se realiza mediante imágenes pre-quirúrgicas, marcos estereotácticos y registros de micro-electrodos (MER). Este último permite visualizar la actividad eléctrica de diferentes estructuras a través del recorrido quirúrgico, cada una de ellas con un patrón de variaciones bien definidas en frecuencia; sin embargo, esto dista de ser un método automático o semi-automático que ayude al neurofisiólogo a tomar decisiones en cuanto a la diana quirúrgica. Con el ánimo de contribuir a la automatización, analizamos tres bandas de frecuencias de señales MER adquiridas en 11 pacientes sometidos a DBS: beta (13-40 Hz), gamma (40-200 Hz) y oscilaciones de alta frecuencia (HFO – 201-400 Hz). Se propusieron y evaluaron 5 índices para detectar el STN: variaciones de parámetros auto-regresivos y su derivada a lo largo del recorrido quirúrgico, la energía de cada banda a partir de la densidad espectral de potencia mediante el método de Yule-Walker, la relación de frecuencias altas a bajas y su derivada. Encontramos que la derivada de un parámetro de la banda beta y la relación alta-bajas de las bandas HFO/gamma alcanzaron errores en la localización del STN, similares a los reportados en la literatura (<2mm). Aunque los índices propuestos son sencillos de calcular y de fácil implementación en tiempo real, se deben seguir explorando para incrementar la capacidad de generalización de los resultados obtenidos

Mapping of subthalamic nucleus using microelectrode recordings during deep brain stimulation

Alongside stereotactic magnetic resonance imaging, microelectrode recording (MER) is frequently used during the deep brain stimulation (DBS) surgery for optimal target localization. The aim of this study is to optimize subthalamic nucleus (STN) mapping using MER analytical patterns. 16 patients underwent bilateral STN-DBS. MER was performed simultaneously for 5 microelectrodes in a setting of Ben's-gun pattern in awake patients. Using spikes and background activity several different parameters and their spectral estimates in various frequency bands including low frequency (2-7 Hz), Alpha (8-12 Hz), Beta (sub-divided as Low_Beta (13-20 Hz) and High_Beta (21-30 Hz)) and Gamma (31 to 49 Hz) were computed. The optimal STN lead placement with the most optimal clinical effect/ side-effect ratio accorded to the maximum spike rate in 85% of the implantation. Mean amplitude of background activity in the low beta frequency range was corresponding to right depth in 85% and right location in 94% of the implantation respectively. MER can be used for STN mapping and intraoperative decisions for the implantation of DBS electrode leads with a high accuracy. Spiking and background activity in the beta range are the most promising independent parameters for the delimitation of the proper anatomical site

Oscillatory activity in the basal ganglia - is it relevant to movement disorders therapy?

Chronic high frequency stimulation of the basal ganglia can be a highly effective intervention for movement disorders in patients. In the past decade, therapeutic benefits have been seen with stimulation of the subthalamic nucleus and globus pallidus interna for Parkinson's disease (PD) and dystonia, respectively. These procedures have allowed direct recording of basal ganglia activity and have suggested that abnormal synchronisation of neurons in these nuclei may contribute to motor impairment. This thesis explores the possible correlation between synchronised activity in the basal ganglia, as evidenced by oscillations in local field potentials, and movement disorders. In Chapter 3, we demonstrate the correlation between synchronization at frequencies under 10 Hz in the globus pallidus interna and dystonic EMG. This low frequency activity is shown to be locked to neuronal activity within GPi in patients with dystonia (Chapter 4). Deep brain stimulation is thought to suppress spontaneous pathological activity in the basal ganglia. Equally, however, it must also suppress any residual physiological activity in these nuclei. In Chapter 5, we demonstrate that the basal ganglia are involved in the processing of simple limb movements in the human, by separating the effects of deep brain stimulation on pathological and physiological activities based on baseline task performance. An impairment of motor performance was seen during high frequency stimulation in those patients with the best task performance at baseline. This deleterious effect, however, should be distinguished from the effect of direct stimulation at 20 Hz in Parkinson's disease. Oscillatory activity at around 20 Hz is thought to be a core feature in Parkinson's disease. In Chapter 6, we demonstrate that the excessive synchronization imposed by stimulation of the subthalamic nucleus at 20 Hz slows movement, in those patients with the best task performance at baseline. This supports the notion that synchronization around 20 Hz may be causally linked to bradykinesia. Last, the therapeutic effectiveness of DBS therapy for patients with PD partially relies on the accurate localisation of the motor region of the subthalamic nucleus. In Chapter 7, we propose an alternative method for the localization of this region using the spontaneous pathological 20 Hz activity to be found in this nucleus. The findings of these studies provide evidence that basal ganglia oscillatory activities of differing frequencies contribute to movement disorders

Customizable Intraoperative Neural Stimulator and Recording System for Deep Brain Stimulation Research and Surgery.

Intraoperative targeting systems provide neurosurgeons with raw electrophysiological data through microelectrodes used for determining location in the brain. There are significant deficits to the available targeting systems, limiting the use in both clinical and research applications. The work presented in this dissertation is of the development and validation of an intraoperative neural stimulator and recording system for use in deep brain stimulation (DBS) surgeries. This intraoperative data acquisition system (IODA) was validated in three applications to ensure efficacy and improvements in research and clinical studies. The first application investigated was a clinical study illustrating the improvement IODA had on the targeting accuracy of DBS leads in the subthalamic nucleus (STN) over current targeting methods. It was demonstrated that the novel navigation algorithm developed for use with IODA targeted microelectrode probe locations significantly closer to final DBS lead positions compared to preoperatively planned trajectory positions. The second study investigated a clinical science application. There are considerable differences in recently published studies for the optimal chronic stimulation site in the STN region. It was shown, using beta oscillations of local field potentials (LFP) recorded by IODA, that optimal stimulation sites were significantly correlated with locations of peak beta activity when DBS leads were medial to the STN midpoint. While DBS lead trajectories lateral of the STN midpoint were significantly correlated with the dorsal border of the STN. The third study explored a basic science application involving the role of the STN in movement inhibition. Through wideband recordings made with IODA, it was shown that the STN is significantly activated during movement and movement inhibition cues as seen in the theta, alpha, and beta bands and single unit activity. Overall the results indicate the utility and adaptability of this system for use within DBS surgeries. There are many applications of IODA for use in research for other neurodegenerative disease including Essential Tremor and Depression. The use of this system has enables neurosurgeons to reduce surgical time, risk, and error for DBS procedures and made entry for those less experienced in this procedure easier.PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/99771/1/dodani_1.pd

Subthalamic Nucleus and Sensorimotor Cortex Activity During Speech Production

The sensorimotor cortex is somatotopically organized to represent the vocal tract articulators such as lips, tongue, larynx, and jaw. How speech and articulatory features are encoded at the subcortical level, however, remains largely unknown. We analyzed LFP recordings from the subthalamic nucleus (STN) and simultaneous electrocorticography recordings from the sensorimotor cortex of 11 human subjects (1 female) with Parkinson´s disease during implantation of deep-brain stimulation (DBS) electrodes while they read aloud three-phoneme words. The initial phonemes involved either articulation primarily with the tongue (coronal consonants) or the lips (labial consonants). We observed significant increases in high-gamma (60?150 Hz) power in both the STN and the sensorimotor cortex that began before speech onset and persisted for the duration of speech articulation. As expected from previous reports, in the sensorimotor cortex, the primary articulators involved in the production of the initial consonants were topographically represented by high-gamma activity. We found that STN high-gamma activity also demonstrated specificity for the primary articulator, although no clear topography was observed. In general, subthalamic high-gamma activity varied along the ventral?dorsal trajectory of the electrodes, with greater high-gamma power recorded in the dorsal locations of the STN. Interestingly, the majority of significant articulator-discriminative activity in the STN occurred before that in sensorimotor cortex. These results demonstrate that articulator-specific speech information is contained within high-gamma activity of the STN, but with different spatial and temporal organization compared with similar information encoded in the sensorimotor cortex.Fil: Chrabaszcz, Anna. University of Pittsburgh; Estados UnidosFil: Neumann, Wolf Julian. Universität zu Berlin; AlemaniaFil: Stretcu, Otilia. University of Pittsburgh; Estados UnidosFil: Lipski, Witold J.. University of Pittsburgh; Estados UnidosFil: Dastolfo Hromack, Christina A.. University of Pittsburgh; Estados UnidosFil: Bush, Alan. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Wang, Dengyu. Tsinghua University; China. University of Pittsburgh; Estados UnidosFil: Crammond, Donald J.. University of Pittsburgh; Estados UnidosFil: Shaiman, Susan. University of Pittsburgh; Estados UnidosFil: Dickey, Michael W.. University of Pittsburgh; Estados UnidosFil: Holt, Lori L.. University of Pittsburgh; Estados UnidosFil: Turner, Robert S.. University of Pittsburgh; Estados UnidosFil: Fiez, Julie A.. University of Pittsburgh; Estados UnidosFil: Richardson, R. Mark. University of Pittsburgh; Estados Unido

Spectral Topography of the Subthalamic Nucleus to Inform Next-Generation Deep Brain Stimulation.

BACKGROUND The landscape of neurophysiological symptoms and behavioral biomarkers in basal ganglia signals for movement disorders is expanding. The clinical translation of sensing-based deep brain stimulation (DBS) also requires a thorough understanding of the anatomical organization of spectral biomarkers within the subthalamic nucleus (STN). OBJECTIVES The aims were to systematically investigate the spectral topography, including a wide range of sub-bands in STN local field potentials (LFP) of Parkinson's disease (PD) patients, and to evaluate its predictive performance for clinical response to DBS. METHODS STN-LFPs were recorded from 70 PD patients (130 hemispheres) awake and at rest using multicontact DBS electrodes. A comprehensive spatial characterization, including hot spot localization and focality estimation, was performed for multiple sub-bands (delta, theta, alpha, low-beta, high-beta, low-gamma, high-gamma, and fast-gamma (FG) as well as low- and fast high-frequency oscillations [HFO]) and compared to the clinical hot spot for rigidity response to DBS. A spectral biomarker map was established and used to predict the clinical response to DBS. RESULTS The STN shows a heterogeneous topographic distribution of different spectral biomarkers, with the strongest segregation in the inferior-superior axis. Relative to the superiorly localized beta hot spot, HFOs (FG, slow HFO) were localized up to 2 mm more inferiorly. Beta oscillations are spatially more spread compared to other sub-bands. Both the spatial proximity of contacts to the beta hot spot and the distance to higher-frequency hot spots were predictive for the best rigidity response to DBS. CONCLUSIONS The spatial segregation and properties of spectral biomarkers within the DBS target structure can additionally be informative for the implementation of next-generation sensing-based DBS. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Characterization of cortico-subthalamic networks during deep brain stimulation surgery in Parkinson’s disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established symptomatic treatment for Parkinson’s diseases (PD). However, knowledge on local electrophysiological biomarkers within the STN and their cortical connectivity profile is still scarce. Such information would be necessary for optimal positioning of the DBS leads based on PD network pathophysiology. This thesis describes the introduction and exploration of a novel technique for electrophysiological measurements during DBS surgery. Combined electroencephalography (EEG) with stepwise local field potentials recordings during insertion of the DBS lead was performed intraoperatively, thereby, allowing to capture local STN and cortico-subthalamic physiology with high speactral and spatial specificity. Our results revealed that strong beta oscillatory activity in the STN was located more dorsally than the STN-ipsilateral motor network phase coupling; the respective frequency bands were in the low and high beta-band, respectively. Moreover, the spot within the STN, where this STN-cortical phase coupling occurred, correlated highly with the STN spot where the phase of beta oscillations modulated the amplitude of high-frequency oscillations. This STN location was furthermore, characterized by information flowed from the ipsilateral motor cortex to the STN in the high beta-band suggesting a pathologically synchronized network with a direct STN-motor cortex connection via the hyperdirect pathway. Interestingly, the very same STN spot showed a resonance like responses to electrical stimulation suggesting a decoupling of pathologically synchronized STN-motor cortex connectivity during therapeutic DBS. In conclusion, this PhD thesis provides first evidence that macroelectrode recordings with the chronic electrode concurrent with EEG recordings are a reliable method for STN localization during DBS surgery. Additionally, combining LFP and EEG recordings during mapping of STN offered a new way of DBS targeting on the basis of pathological local biomarkers and network activity

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