Electro-Quasistatic Simulations in Bio-Systems Engineering and Medical Engineering

NASA Astrophysics Data System (ADS)

van Rienen, U.; Flehr, J.; Schreiber, U.; Schulze, S.; Gimsa, U.; Baumann, W.; Weiss, D. G.; Gimsa, J.; Benecke, R.; Pau, H.-W.

2005-05-01

Slowly varying electromagnetic fields play a key role in various applications in bio-systems and medical engineering. Examples are the electric activity of neurons on neurochips used as biosensors, the stimulating electric fields of implanted electrodes used for deep brain stimulation in patients with Morbus Parkinson and the stimulation of the auditory nerves in deaf patients, respectively. In order to simulate the neuronal activity on a chip it is necessary to couple Maxwell's and Hodgkin-Huxley's equations. First numerical results for a neuron coupling to a single electrode are presented. They show a promising qualitative agreement with the experimentally recorded signals. Further, simulations are presented on electrodes for deep brain stimulation in animal experiments where the question of electrode ageing and energy deposition in the surrounding tissue are of major interest. As a last example, electric simulations for a simple cochlea model are presented comparing the field in the skull bones for different electrode types and stimulations in different positions.

Tractography patterns of subthalamic nucleus deep brain stimulation.

PubMed

Vanegas-Arroyave, Nora; Lauro, Peter M; Huang, Ling; Hallett, Mark; Horovitz, Silvina G; Zaghloul, Kareem A; Lungu, Codrin

2016-04-01

Deep brain stimulation therapy is an effective symptomatic treatment for Parkinson's disease, yet the precise mechanisms responsible for its therapeutic effects remain unclear. Although the targets of deep brain stimulation are grey matter structures, axonal modulation is known to play an important role in deep brain stimulation's therapeutic mechanism. Several white matter structures in proximity to the subthalamic nucleus have been implicated in the clinical benefits of deep brain stimulation for Parkinson's disease. We assessed the connectivity patterns that characterize clinically beneficial electrodes in Parkinson's disease patients, after deep brain stimulation of the subthalamic nucleus. We evaluated 22 patients with Parkinson's disease (11 females, age 57 ± 9.1 years, disease duration 13.3 ± 6.3 years) who received bilateral deep brain stimulation of the subthalamic nucleus at the National Institutes of Health. During an initial electrode screening session, one month after deep brain stimulation implantation, the clinical benefits of each contact were determined. The electrode was localized by coregistering preoperative magnetic resonance imaging and postoperative computer tomography images and the volume of tissue activated was estimated from stimulation voltage and impedance. Brain connectivity for the volume of tissue activated of deep brain stimulation contacts was assessed using probabilistic tractography with diffusion-tensor data. Areas most frequently connected to clinically effective contacts included the thalamus, substantia nigra, brainstem and superior frontal gyrus. A series of discriminant analyses demonstrated that the strength of connectivity to the superior frontal gyrus and the thalamus were positively associated with clinical effectiveness. The connectivity patterns observed in our study suggest that the modulation of white matter tracts directed to the superior frontal gyrus and the thalamus is associated with favourable clinical outcomes and may contribute to the therapeutic effects of deep brain stimulation. Our method can be further developed to reliably identify effective deep brain stimulation contacts and aid in the programming process. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Design of electrodes and current limits for low frequency electrical impedance tomography of the brain.

PubMed

Gilad, O; Horesh, L; Holder, D S

2007-07-01

For the novel application of recording of resistivity changes related to neuronal depolarization in the brain with electrical impedance tomography, optimal recording is with applied currents below 100 Hz, which might cause neural stimulation of skin or underlying brain. The purpose of this work was to develop a method for application of low frequency currents to the scalp, which delivered the maximum current without significant stimulation of skin or underlying brain. We propose a recessed electrode design which enabled current injection with an acceptable skin sensation to be increased from 100 muA using EEG electrodes, to 1 mA in 16 normal volunteers. The effect of current delivered to the brain was assessed with an anatomically realistic finite element model of the adult head. The modelled peak cerebral current density was 0.3 A/m(2), which was 5 to 25-fold less than the threshold for stimulation of the brain estimated from literature review.

Design and in vivo evaluation of more efficient and selective deep brain stimulation electrodes

NASA Astrophysics Data System (ADS)

Howell, Bryan; Huynh, Brian; Grill, Warren M.

2015-08-01

Objective. Deep brain stimulation (DBS) is an effective treatment for movement disorders and a promising therapy for treating epilepsy and psychiatric disorders. Despite its clinical success, the efficiency and selectivity of DBS can be improved. Our objective was to design electrode geometries that increased the efficiency and selectivity of DBS. Approach. We coupled computational models of electrodes in brain tissue with cable models of axons of passage (AOPs), terminating axons (TAs), and local neurons (LNs); we used engineering optimization to design electrodes for stimulating these neural elements; and the model predictions were tested in vivo. Main results. Compared with the standard electrode used in the Medtronic Model 3387 and 3389 arrays, model-optimized electrodes consumed 45-84% less power. Similar gains in selectivity were evident with the optimized electrodes: 50% of parallel AOPs could be activated while reducing activation of perpendicular AOPs from 44 to 48% with the standard electrode to 0-14% with bipolar designs; 50% of perpendicular AOPs could be activated while reducing activation of parallel AOPs from 53 to 55% with the standard electrode to 1-5% with an array of cathodes; and, 50% of TAs could be activated while reducing activation of AOPs from 43 to 100% with the standard electrode to 2-15% with a distal anode. In vivo, both the geometry and polarity of the electrode had a profound impact on the efficiency and selectivity of stimulation. Significance. Model-based design is a powerful tool that can be used to improve the efficiency and selectivity of DBS electrodes.

Comparison of effectiveness between cork-screw and peg-screw electrodes for transcranial motor evoked potential monitoring using the finite element method.

PubMed

Tomio, Ryosuke; Akiyama, Takenori; Ohira, Takayuki; Yoshida, Kazunari

2016-01-01

Intraoperative monitoring of motor evoked potentials by transcranial electric stimulation is popular in neurosurgery for monitoring motor function preservation. Some authors have reported that the peg-screw electrodes screwed into the skull can more effectively conduct current to the brain compared to subdermal cork-screw electrodes screwed into the skin. The aim of this study was to investigate the influence of electrode design on transcranial motor evoked potential monitoring. We estimated differences in effectiveness between the cork-screw electrode, peg-screw electrode, and cortical electrode to produce electric fields in the brain. We used the finite element method to visualize electric fields in the brain generated by transcranial electric stimulation using realistic three-dimensional head models developed from T1-weighted images. Surfaces from five layers of the head were separated as accurately as possible. We created the "cork-screws model," "1 peg-screw model," "peg-screws model," and "cortical electrode model". Electric fields in the brain radially diffused from the brain surface at a maximum just below the electrodes in coronal sections. The coronal sections and surface views of the brain showed higher electric field distributions under the peg-screw compared to the cork-screw. An extremely high electric field was observed under cortical electrodes. Our main finding was that the intensity of electric fields in the brain are higher in the peg-screw model than the cork-screw model.

Towards a Switched-Capacitor Based Stimulator for Efficient Deep-Brain Stimulation

PubMed Central

Vidal, Jose; Ghovanloo, Maysam

2013-01-01

We have developed a novel 4-channel prototype stimulation circuit for implantable neurological stimulators (INS). This Switched-Capacitor based Stimulator (SCS) aims to utilize charge storage and charge injection techniques to take advantage of both the efficiency of conventional voltage-controlled stimulators (VCS) and the safety and controllability of current-controlled stimulators (CCS). The discrete SCS prototype offers fine control over stimulation parameters such as voltage, current, pulse width, frequency, and active electrode channel via a LabVIEW graphical user interface (GUI) when connected to a PC through USB. Furthermore, the prototype utilizes a floating current sensor to provide charge-balanced biphasic stimulation and ensure safety. The stimulator was analyzed using an electrode-electrolyte interface (EEI) model as well as with a pair of pacing electrodes in saline. The primary motivation of this research is to test the feasibility and functionality of a safe, effective, and power-efficient switched-capacitor based stimulator for use in Deep Brain Stimulation. PMID:21095987

Electrical stimulation of a small brain area reversibly disrupts consciousness.

PubMed

Koubeissi, Mohamad Z; Bartolomei, Fabrice; Beltagy, Abdelrahman; Picard, Fabienne

2014-08-01

The neural mechanisms that underlie consciousness are not fully understood. We describe a region in the human brain where electrical stimulation reproducibly disrupted consciousness. A 54-year-old woman with intractable epilepsy underwent depth electrode implantation and electrical stimulation mapping. The electrode whose stimulation disrupted consciousness was between the left claustrum and anterior-dorsal insula. Stimulation of electrodes within 5mm did not affect consciousness. We studied the interdependencies among depth recording signals as a function of time by nonlinear regression analysis (h(2) coefficient) during stimulations that altered consciousness and stimulations of the same electrode at lower current intensities that were asymptomatic. Stimulation of the claustral electrode reproducibly resulted in a complete arrest of volitional behavior, unresponsiveness, and amnesia without negative motor symptoms or mere aphasia. The disruption of consciousness did not outlast the stimulation and occurred without any epileptiform discharges. We found a significant increase in correlation for interactions affecting medial parietal and posterior frontal channels during stimulations that disrupted consciousness compared with those that did not. Our findings suggest that the left claustrum/anterior insula is an important part of a network that subserves consciousness and that disruption of consciousness is related to increased EEG signal synchrony within frontal-parietal networks. Copyright © 2014 Elsevier Inc. All rights reserved.

Safety parameter considerations of anodal transcranial Direct Current Stimulation in rats.

PubMed

Jackson, Mark P; Truong, Dennis; Brownlow, Milene L; Wagner, Jessica A; McKinley, R Andy; Bikson, Marom; Jankord, Ryan

2017-08-01

A commonly referenced transcranial Direct Current Stimulation (tDCS) safety threshold derives from tDCS lesion studies in the rat and relies on electrode current density (and related electrode charge density) to support clinical guidelines. Concerns about the role of polarity (e.g. anodal tDCS), sub-lesion threshold injury (e.g. neuroinflammatory processes), and role of electrode montage across rodent and human studies support further investigation into animal models of tDCS safety. Thirty-two anesthetized rats received anodal tDCS between 0 and 5mA for 60min through one of three epicranial electrode montages. Tissue damage was evaluated using hemotoxylin and eosin (H&E) staining, Iba-1 immunohistochemistry, and computational brain current density modeling. Brain lesion occurred after anodal tDCS at and above 0.5mA using a 25.0mm 2 electrode (electrode current density: 20.0A/m 2 ). Lesion initially occurred using smaller 10.6mm 2 or 5.3mm 2 electrodes at 0.25mA (23.5A/m 2 ) and 0.5mA (94.2A/m 2 ), respectively. Histological damage was correlated with computational brain current density predictions. Changes in microglial phenotype occurred in higher stimulation groups. Lesions were observed using anodal tDCS at an electrode current density of 20.0A/m 2 , which is below the previously reported safety threshold of 142.9A/m 2 using cathodal tDCS. The lesion area is not simply predicted by electrode current density (and so not by charge density as duration was fixed); rather computational modeling suggests average brain current density as a better predictor for anodal tDCS. Nonetheless, under the assumption that rodent epicranial stimulation is a hypersensitive model, an electrode current density of 20.0A/m 2 represents a conservative threshold for clinical tDCS, which typically uses an electrode current density of 2A/m 2 when electrodes are placed on the skin (resulting in a lower brain current density). Copyright © 2017 Elsevier Inc. All rights reserved.

Spatial and polarity precision of concentric high-definition transcranial direct current stimulation (HD-tDCS)

NASA Astrophysics Data System (ADS)

Alam, Mahtab; Truong, Dennis Q.; Khadka, Niranjan; Bikson, Marom

2016-06-01

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that applies low amplitude current via electrodes placed on the scalp. Rather than directly eliciting a neuronal response, tDCS is believed to modulate excitability—enhancing or suppressing neuronal activity in regions of the brain depending on the polarity of stimulation. The specificity of tDCS to any therapeutic application derives in part from how electrode configuration determines the brain regions that are stimulated. Conventional tDCS uses two relatively large pads (>25 cm2) whereas high-definition tDCS (HD-tDCS) uses arrays of smaller electrodes to enhance brain targeting. The 4  ×  1 concentric ring HD-tDCS (one center electrode surrounded by four returns) has been explored in application where focal targeting of cortex is desired. Here, we considered optimization of concentric ring HD-tDCS for targeting: the role of electrodes in the ring and the ring’s diameter. Finite element models predicted cortical electric field generated during tDCS. High resolution MRIs were segmented into seven tissue/material masks of varying conductivities. Computer aided design (CAD) model of electrodes, gel, and sponge pads were incorporated into the segmentation. Volume meshes were generated and the Laplace equation (\

Regional anatomy of the pedunculopontine nucleus: relevance for deep brain stimulation.

PubMed

Fournier-Gosselin, Marie-Pierre; Lipsman, Nir; Saint-Cyr, Jean A; Hamani, Clement; Lozano, Andres M

2013-09-01

The pedunculopontine nucleus (PPN) is currently being investigated as a potential deep brain stimulation target to improve gait and posture in Parkinson's disease. This review examines the complex anatomy of the PPN region and suggests a functional mapping of the surrounding nuclei and fiber tracts that may serve as a guide to a more accurate placement of electrodes while avoiding potentially adverse effects. The relationships of the PPN were examined in different human brain atlases. Schematic representations of those structures in the vicinity of the PPN were generated and correlated with their potential stimulation effects. By providing a functional map and representative schematics of the PPN region, we hope to optimize the placement of deep brain stimulation electrodes, thereby maximizing safety and clinical efficacy. © 2013 International Parkinson and Movement Disorder Society.

Analyzing the tradeoff between electrical complexity and accuracy in patient-specific computational models of deep brain stimulation.

PubMed

Howell, Bryan; McIntyre, Cameron C

2016-06-01

Deep brain stimulation (DBS) is an adjunctive therapy that is effective in treating movement disorders and shows promise for treating psychiatric disorders. Computational models of DBS have begun to be utilized as tools to optimize the therapy. Despite advancements in the anatomical accuracy of these models, there is still uncertainty as to what level of electrical complexity is adequate for modeling the electric field in the brain and the subsequent neural response to the stimulation. We used magnetic resonance images to create an image-based computational model of subthalamic DBS. The complexity of the volume conductor model was increased by incrementally including heterogeneity, anisotropy, and dielectric dispersion in the electrical properties of the brain. We quantified changes in the load of the electrode, the electric potential distribution, and stimulation thresholds of descending corticofugal (DCF) axon models. Incorporation of heterogeneity altered the electric potentials and subsequent stimulation thresholds, but to a lesser degree than incorporation of anisotropy. Additionally, the results were sensitive to the choice of method for defining anisotropy, with stimulation thresholds of DCF axons changing by as much as 190%. Typical approaches for defining anisotropy underestimate the expected load of the stimulation electrode, which led to underestimation of the extent of stimulation. More accurate predictions of the electrode load were achieved with alternative approaches for defining anisotropy. The effects of dielectric dispersion were small compared to the effects of heterogeneity and anisotropy. The results of this study help delineate the level of detail that is required to accurately model electric fields generated by DBS electrodes.

Analyzing the tradeoff between electrical complexity and accuracy in patient-specific computational models of deep brain stimulation

NASA Astrophysics Data System (ADS)

Howell, Bryan; McIntyre, Cameron C.

2016-06-01

Objective. Deep brain stimulation (DBS) is an adjunctive therapy that is effective in treating movement disorders and shows promise for treating psychiatric disorders. Computational models of DBS have begun to be utilized as tools to optimize the therapy. Despite advancements in the anatomical accuracy of these models, there is still uncertainty as to what level of electrical complexity is adequate for modeling the electric field in the brain and the subsequent neural response to the stimulation. Approach. We used magnetic resonance images to create an image-based computational model of subthalamic DBS. The complexity of the volume conductor model was increased by incrementally including heterogeneity, anisotropy, and dielectric dispersion in the electrical properties of the brain. We quantified changes in the load of the electrode, the electric potential distribution, and stimulation thresholds of descending corticofugal (DCF) axon models. Main results. Incorporation of heterogeneity altered the electric potentials and subsequent stimulation thresholds, but to a lesser degree than incorporation of anisotropy. Additionally, the results were sensitive to the choice of method for defining anisotropy, with stimulation thresholds of DCF axons changing by as much as 190%. Typical approaches for defining anisotropy underestimate the expected load of the stimulation electrode, which led to underestimation of the extent of stimulation. More accurate predictions of the electrode load were achieved with alternative approaches for defining anisotropy. The effects of dielectric dispersion were small compared to the effects of heterogeneity and anisotropy. Significance. The results of this study help delineate the level of detail that is required to accurately model electric fields generated by DBS electrodes.

Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain.

PubMed

Van Den Berge, Nathalie; Vanhove, Christian; Descamps, Benedicte; Dauwe, Ine; van Mierlo, Pieter; Vonck, Kristl; Keereman, Vincent; Raedt, Robrecht; Boon, Paul; Van Holen, Roel

2015-01-01

Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS.

Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain

PubMed Central

Van Den Berge, Nathalie; Vanhove, Christian; Descamps, Benedicte; Dauwe, Ine; van Mierlo, Pieter; Vonck, Kristl; Keereman, Vincent; Raedt, Robrecht; Boon, Paul; Van Holen, Roel

2015-01-01

Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS. PMID:26193653

Interfacing with the brain using organic electronics (Presentation Recording)

NASA Astrophysics Data System (ADS)

Malliaras, George G.

2015-10-01

Implantable electrodes are being used for diagnostic purposes, for brain-machine interfaces, and for delivering electrical stimulation to alleviate the symptoms of diseases such as Parkinson's. The field of organic electronics made available devices with a unique combination of attractive properties, including mixed ionic/electronic conduction, mechanical flexibility, enhanced biocompatibility, and capability for drug delivery. I will present examples of organic electrodes, transistors and other devices for recording and stimulation of brain activity and discuss how they can improve our understanding of brain physiology and pathology, and how they can be used to deliver new therapies.

Carbon Nanofiber Nanoelectrodes for Neural Stimulation and Chemical Detection: The Era of "Smart" Deep Brain Stimulation

NASA Technical Reports Server (NTRS)

Koehne, Jessica E.

2016-01-01

A sensor platform based on vertically aligned carbon nanofibers (CNFs) has been developed. Their inherent nanometer scale, high conductivity, wide potential window, good biocompatibility and well-defined surface chemistry make them ideal candidates as biosensor electrodes. Here, we report two studies using vertically aligned CNF nanoelectrodes for biomedical applications. CNF arrays are investigated as neural stimulation and neurotransmitter recording electrodes for application in deep brain stimulation (DBS). Polypyrrole coated CNF nanoelectrodes have shown great promise as stimulating electrodes due to their large surface area, low impedance, biocompatibility and capacity for highly localized stimulation. CNFs embedded in SiO2 have been used as sensing electrodes for neurotransmitter detection. Our approach combines a multiplexed CNF electrode chip, developed at NASA Ames Research Center, with the Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS) system, developed at the Mayo Clinic. Preliminary results indicate that the CNF nanoelectrode arrays are easily integrated with WINCS for neurotransmitter detection in a multiplexed array format. In the future, combining CNF based stimulating and recording electrodes with WINCS may lay the foundation for an implantable smart therapeutic system that utilizes neurochemical feedback control while likely resulting in increased DBS application in various neuropsychiatric disorders. In total, our goal is to take advantage of the nanostructure of CNF arrays for biosensing studies requiring ultrahigh sensitivity, high-degree of miniaturization, and selective biofunctionalization.

Carbon Nanofiber Nanoelectrodes for Neural Stimulation and Chemical Detection: The Era of Smart Deep Brain Stimulation

NASA Technical Reports Server (NTRS)

Koehne, Jessica E.

2016-01-01

A sensor platform based on vertically aligned carbon nanofibers (CNFs) has been developed. Their inherent nanometer scale, high conductivity, wide potential window, good biocompatibility and well-defined surface chemistry make them ideal candidates as biosensor electrodes. Here, we report two studies using vertically aligned CNF nanoelectrodes for biomedical applications. CNF arrays are investigated as neural stimulation and neurotransmitter recording electrodes for application in deep brain stimulation (DBS). Polypyrrole coated CNF nanoelectrodes have shown great promise as stimulating electrodes due to their large surface area, low impedance, biocompatibility and capacity for highly localized stimulation. CNFs embedded in SiO2 have been used as sensing electrodes for neurotransmitter detection. Our approach combines a multiplexed CNF electrode chip, developed at NASA Ames Research Center, with the Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS) system, developed at the Mayo Clinic. Preliminary results indicate that the CNF nanoelectrode arrays are easily integrated with WINCS for neurotransmitter detection in a multiplexed array format. In the future, combining CNF based stimulating and recording electrodes with WINCS may lay the foundation for an implantable "smart" therapeutic system that utilizes neurochemical feedback control while likely resulting in increased DBS application in various neuropsychiatric disorders. In total, our goal is to take advantage of the nanostructure of CNF arrays for biosensing studies requiring ultrahigh sensitivity, high-degree of miniaturization, and selective biofunctionalization.

Non-Invasive Electrical Brain Stimulation Montages for Modulation of Human Motor Function.

PubMed

Curado, Marco; Fritsch, Brita; Reis, Janine

2016-02-04

Non-invasive electrical brain stimulation (NEBS) is used to modulate brain function and behavior, both for research and clinical purposes. In particular, NEBS can be applied transcranially either as direct current stimulation (tDCS) or alternating current stimulation (tACS). These stimulation types exert time-, dose- and in the case of tDCS polarity-specific effects on motor function and skill learning in healthy subjects. Lately, tDCS has been used to augment the therapy of motor disabilities in patients with stroke or movement disorders. This article provides a step-by-step protocol for targeting the primary motor cortex with tDCS and transcranial random noise stimulation (tRNS), a specific form of tACS using an electrical current applied randomly within a pre-defined frequency range. The setup of two different stimulation montages is explained. In both montages the emitting electrode (the anode for tDCS) is placed on the primary motor cortex of interest. For unilateral motor cortex stimulation the receiving electrode is placed on the contralateral forehead while for bilateral motor cortex stimulation the receiving electrode is placed on the opposite primary motor cortex. The advantages and disadvantages of each montage for the modulation of cortical excitability and motor function including learning are discussed, as well as safety, tolerability and blinding aspects.

Carbon nanotube yarns for deep brain stimulation electrode.

PubMed

Jiang, Changqing; Li, Luming; Hao, Hongwei

2011-12-01

A new form of deep brain stimulation (DBS) electrode was proposed that was made of carbon nanotube yarns (CNTYs). Electrode interface properties were examined using cyclic voltammetry (CV) and electrochemical impedance spectrum (EIS). The CNTY electrode interface exhibited large charge storage capacity (CSC) of 12.3 mC/cm(2) which increased to 98.6 mC/cm(2) after acid treatment, compared with 5.0 mC/cm(2) of Pt-Ir. Impedance spectrum of both untreated and treated CNTY electrodes showed that finite diffusion process occurred at the interface due to their porous structure and charge was delivered through capacitive mechanism. To evaluate stability electrical stimulus was exerted for up to 72 h and CV and EIS results of CNTY electrodes revealed little alteration. Therefore CNTY could make a good electrode material for DBS.

21 CFR 882.5840 - Implanted intracerebral/subcortical stimulator for pain relief.

Code of Federal Regulations, 2013 CFR

2013-04-01

... to subsurface areas of a patient's brain to treat severe intractable pain. The stimulator consists of an implanted receiver with electrodes that are placed within a patient's brain and an external...

21 CFR 882.5840 - Implanted intracerebral/subcortical stimulator for pain relief.

Code of Federal Regulations, 2012 CFR

2012-04-01

... to subsurface areas of a patient's brain to treat severe intractable pain. The stimulator consists of an implanted receiver with electrodes that are placed within a patient's brain and an external...

21 CFR 882.5840 - Implanted intracerebral/subcortical stimulator for pain relief.

Code of Federal Regulations, 2010 CFR

2010-04-01

... to subsurface areas of a patient's brain to treat severe intractable pain. The stimulator consists of an implanted receiver with electrodes that are placed within a patient's brain and an external...

21 CFR 882.5840 - Implanted intracerebral/subcortical stimulator for pain relief.

Code of Federal Regulations, 2014 CFR

2014-04-01

... to subsurface areas of a patient's brain to treat severe intractable pain. The stimulator consists of an implanted receiver with electrodes that are placed within a patient's brain and an external...

21 CFR 882.5840 - Implanted intracerebral/subcortical stimulator for pain relief.

Code of Federal Regulations, 2011 CFR

2011-04-01

... to subsurface areas of a patient's brain to treat severe intractable pain. The stimulator consists of an implanted receiver with electrodes that are placed within a patient's brain and an external...

MRI-induced heating of deep brain stimulation leads

NASA Astrophysics Data System (ADS)

Mohsin, Syed A.; Sheikh, Noor M.; Saeed, Usman

2008-10-01

The radiofrequency (RF) field used in magnetic resonance imaging is scattered by medical implants. The scattered field of a deep brain stimulation lead can be very intense near the electrodes stimulating the brain. The effect is more pronounced if the lead behaves as a resonant antenna. In this paper, we examine the resonant length effect. We also use the finite element method to compute the near field for (i) the lead immersed in inhomogeneous tissue (fat, muscle, and brain tissues) and (ii) the lead connected to an implantable pulse generator. Electric field, specific absorption rate and induced temperature rise distributions have been obtained in the brain tissue surrounding the electrodes. The worst-case scenario has been evaluated by neglecting the effect of blood perfusion. The computed values are in good agreement with in vitro measurements made in the laboratory.

PaCER - A fully automated method for electrode trajectory and contact reconstruction in deep brain stimulation.

PubMed

Husch, Andreas; V Petersen, Mikkel; Gemmar, Peter; Goncalves, Jorge; Hertel, Frank

2018-01-01

Deep brain stimulation (DBS) is a neurosurgical intervention where electrodes are permanently implanted into the brain in order to modulate pathologic neural activity. The post-operative reconstruction of the DBS electrodes is important for an efficient stimulation parameter tuning. A major limitation of existing approaches for electrode reconstruction from post-operative imaging that prevents the clinical routine use is that they are manual or semi-automatic, and thus both time-consuming and subjective. Moreover, the existing methods rely on a simplified model of a straight line electrode trajectory, rather than the more realistic curved trajectory. The main contribution of this paper is that for the first time we present a highly accurate and fully automated method for electrode reconstruction that considers curved trajectories. The robustness of our proposed method is demonstrated using a multi-center clinical dataset consisting of N  = 44 electrodes. In all cases the electrode trajectories were successfully identified and reconstructed. In addition, the accuracy is demonstrated quantitatively using a high-accuracy phantom with known ground truth. In the phantom experiment, the method could detect individual electrode contacts with high accuracy and the trajectory reconstruction reached an error level below 100 μm (0.046 ± 0.025 mm). An implementation of the method is made publicly available such that it can directly be used by researchers or clinicians. This constitutes an important step towards future integration of lead reconstruction into standard clinical care.

A novel combinational approach of microstimulation and bioluminescence imaging to study the mechanisms of action of cerebral electrical stimulation in mice

PubMed Central

Arsenault, Dany; Drouin-Ouellet, Janelle; Saint-Pierre, Martine; Petrou, Petros; Dubois, Marilyn; Kriz, Jasna; Barker, Roger A; Cicchetti, Antonio; Cicchetti, Francesca

2015-01-01

Key points We have developed a unique prototype to perform brain stimulation in mice. This system presents a number of advantages and new developments: 1) all stimulation parameters can be adjusted, 2) both positive and negative current pulses can be generated, guaranteeing electrically balanced stimulation regimen, 3) which can be produced with both low and high impedance electrodes, 4) the developed electrodes ensure localized stimulation and 5) can be used to stimulate and/or record brain potential and 6) in vivo recording of electric pulses allows the detection of defective electrodes (wire breakage or short circuits). This new micro-stimulator device further allows simultaneous live bioluminescence imaging of the mouse brain, enabling real time assessment of the impact of stimulation on cerebral tissue. The use of this novel tool in various transgenic mouse models of disease opens up a whole new range of possibilities in better understanding brain stimulation. Abstract Deep brain stimulation (DBS) is used to treat a number of neurological conditions and is currently being tested to intervene in neuropsychiatric conditions. However, a better understanding of how it works would ensure that side effects could be minimized and benefits optimized. We have thus developed a unique device to perform brain stimulation (BS) in mice and to address fundamental issues related to this methodology in the pre-clinical setting. This new microstimulator prototype was specifically designed to allow simultaneous live bioluminescence imaging of the mouse brain, allowing real time assessment of the impact of stimulation on cerebral tissue. We validated the authenticity of this tool in vivo by analysing the expression of toll-like receptor 2 (TLR2), corresponding to the microglial response, in the stimulated brain regions of TLR2-fluc-GFP transgenic mice, which we further corroborated with post-mortem analyses in these animals as well as in human brains of patients who underwent DBS to treat their Parkinson's disease. In the present study, we report on the development of the first BS device that allows for simultaneous live in vivo imaging in mice. This tool opens up a whole new range of possibilities that allow a better understanding of BS and how to optimize its effects through its use in murine models of disease. PMID:25653107

Using transcranial direct-current stimulation (tDCS) to understand cognitive processing.

PubMed

Reinhart, Robert M G; Cosman, Josh D; Fukuda, Keisuke; Woodman, Geoffrey F

2017-01-01

Noninvasive brain stimulation methods are becoming increasingly common tools in the kit of the cognitive scientist. In particular, transcranial direct-current stimulation (tDCS) is showing great promise as a tool to causally manipulate the brain and understand how information is processed. The popularity of this method of brain stimulation is based on the fact that it is safe, inexpensive, its effects are long lasting, and you can increase the likelihood that neurons will fire near one electrode and decrease the likelihood that neurons will fire near another. However, this method of manipulating the brain to draw causal inferences is not without complication. Because tDCS methods continue to be refined and are not yet standardized, there are reports in the literature that show some striking inconsistencies. Primary among the complications of the technique is that the tDCS method uses two or more electrodes to pass current and all of these electrodes will have effects on the tissue underneath them. In this tutorial, we will share what we have learned about using tDCS to manipulate how the brain perceives, attends, remembers, and responds to information from our environment. Our goal is to provide a starting point for new users of tDCS and spur discussion of the standardization of methods to enhance replicability.

Using transcranial direct-current stimulation (tDCS) to understand cognitive processing

PubMed Central

Reinhart, Robert M.G.; Cosman, Josh D.; Fukuda, Keisuke; Woodman, Geoffrey F.

2017-01-01

Noninvasive brain stimulation methods are becoming increasingly common tools in the kit of the cognitive scientist. In particular, transcranial direct-current stimulation (tDCS) is showing great promise as a tool to causally manipulate the brain and understand how information is processed. The popularity of this method of brain stimulation is based on the fact that it is safe, inexpensive, its effects are long lasting, and you can increase the likelihood that neurons will fire near one electrode and decrease the likelihood that neurons will fire near another. However, this method of manipulating the brain to draw causal inferences is not without complication. Because tDCS methods continue to be refined and are not yet standardized, there are reports in the literature that show some striking inconsistencies. Primary among the complications of the technique is that the tDCS method uses two or more electrodes to pass current and all of these electrodes will have effects on the tissue underneath them. In this tutorial, we will share what we have learned about using tDCS to manipulate how the brain perceives, attends, remembers, and responds to information from our environment. Our goal is to provide a starting point for new users of tDCS and spur discussion of the standardization of methods to enhance replicability. PMID:27804033

Spatial and polarity precision of concentric high-definition transcranial direct current stimulation (HD-tDCS).

PubMed

Alam, Mahtab; Truong, Dennis Q; Khadka, Niranjan; Bikson, Marom

2016-06-21

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that applies low amplitude current via electrodes placed on the scalp. Rather than directly eliciting a neuronal response, tDCS is believed to modulate excitability-enhancing or suppressing neuronal activity in regions of the brain depending on the polarity of stimulation. The specificity of tDCS to any therapeutic application derives in part from how electrode configuration determines the brain regions that are stimulated. Conventional tDCS uses two relatively large pads (>25 cm(2)) whereas high-definition tDCS (HD-tDCS) uses arrays of smaller electrodes to enhance brain targeting. The 4  ×  1 concentric ring HD-tDCS (one center electrode surrounded by four returns) has been explored in application where focal targeting of cortex is desired. Here, we considered optimization of concentric ring HD-tDCS for targeting: the role of electrodes in the ring and the ring's diameter. Finite element models predicted cortical electric field generated during tDCS. High resolution MRIs were segmented into seven tissue/material masks of varying conductivities. Computer aided design (CAD) model of electrodes, gel, and sponge pads were incorporated into the segmentation. Volume meshes were generated and the Laplace equation ([Formula: see text] · (σ [Formula: see text] V)  =  0) was solved for cortical electric field, which was interpreted using physiological assumptions to correlate with stimulation and modulation. Cortical field intensity was predicted to increase with increasing ring diameter at the cost of focality while uni-directionality decreased. Additional surrounding ring electrodes increased uni-directionality while lowering cortical field intensity and increasing focality; though, this effect saturated and more than 4 surround electrode would not be justified. Using a range of concentric HD-tDCS montages, we showed that cortical region of influence can be controlled while balancing other design factors such as intensity at the target and uni-directionality. Furthermore, the evaluated concentric HD-tDCS approaches can provide categorical improvements in targeting compared to conventional tDCS. Hypothesis driven clinical trials, based on specific target engagement, would benefit by this more precise method of stimulation that could avoid potentially confounding brain regions.

Ultrasoft microwire neural electrodes improve chronic tissue integration.

PubMed

Du, Zhanhong Jeff; Kolarcik, Christi L; Kozai, Takashi D Y; Luebben, Silvia D; Sapp, Shawn A; Zheng, Xin Sally; Nabity, James A; Cui, X Tracy

2017-04-15

Chronically implanted neural multi-electrode arrays (MEA) are an essential technology for recording electrical signals from neurons and/or modulating neural activity through stimulation. However, current MEAs, regardless of the type, elicit an inflammatory response that ultimately leads to device failure. Traditionally, rigid materials like tungsten and silicon have been employed to interface with the relatively soft neural tissue. The large stiffness mismatch is thought to exacerbate the inflammatory response. In order to minimize the disparity between the device and the brain, we fabricated novel ultrasoft electrodes consisting of elastomers and conducting polymers with mechanical properties much more similar to those of brain tissue than previous neural implants. In this study, these ultrasoft microelectrodes were inserted and released using a stainless steel shuttle with polyethyleneglycol (PEG) glue. The implanted microwires showed functionality in acute neural stimulation. When implanted for 1 or 8weeks, the novel soft implants demonstrated significantly reduced inflammatory tissue response at week 8 compared to tungsten wires of similar dimension and surface chemistry. Furthermore, a higher degree of cell body distortion was found next to the tungsten implants compared to the polymer implants. Our results support the use of these novel ultrasoft electrodes for long term neural implants. One critical challenge to the translation of neural recording/stimulation electrode technology to clinically viable devices for brain computer interface (BCI) or deep brain stimulation (DBS) applications is the chronic degradation of device performance due to the inflammatory tissue reaction. While many hypothesize that soft and flexible devices elicit reduced inflammatory tissue responses, there has yet to be a rigorous comparison between soft and stiff implants. We have developed an ultra-soft microelectrode with Young's modulus lower than 1MPa, closely mimicking the brain tissue modulus. Here, we present a rigorous histological comparison of this novel ultrasoft electrode and conventional stiff electrode with the same size, shape and surface chemistry, implanted in rat brains for 1-week and 8-weeks. Significant improvement was observed for ultrasoft electrodes, including inflammatory tissue reaction, electrode-tissue integration as well as mechanical disturbance to nearby neurons. A full spectrum of new techniques were developed in this study, from insertion shuttle to in situ sectioning of the microelectrode to automated cell shape analysis, all of which should contribute new methods to the field. Finally, we showed the electrical functionality of the ultrasoft electrode, demonstrating the potential of flexible neural implant devices for future research and clinical use. Copyright © 2017. Published by Elsevier Ltd.

Recording and Modulation of Epileptiform Activity in Rodent Brain Slices Coupled to Microelectrode Arrays.

PubMed

Panuccio, Gabriella; Colombi, Ilaria; Chiappalone, Michela

2018-05-15

Temporal lobe epilepsy (TLE) is the most common partial complex epileptic syndrome and the least responsive to medications. Deep brain stimulation (DBS) is a promising approach when pharmacological treatment fails or neurosurgery is not recommended. Acute brain slices coupled to microelectrode arrays (MEAs) represent a valuable tool to study neuronal network interactions and their modulation by electrical stimulation. As compared to conventional extracellular recording techniques, they provide the added advantages of a greater number of observation points and a known inter-electrode distance, which allow studying the propagation path and speed of electrophysiological signals. However, tissue oxygenation may be greatly impaired during MEA recording, requiring a high perfusion rate, which comes at the cost of decreased signal-to-noise ratio and higher oscillations in the experimental temperature. Electrical stimulation further stresses the brain tissue, making it difficult to pursue prolonged recording/stimulation epochs. Moreover, electrical modulation of brain slice activity needs to target specific structures/pathways within the brain slice, requiring that electrode mapping be easily and quickly performed live during the experiment. Here, we illustrate how to perform the recording and electrical modulation of 4-aminopyridine (4AP)-induced epileptiform activity in rodent brain slices using planar MEAs. We show that the brain tissue obtained from mice outperforms rat brain tissue and is thus better suited for MEA experiments. This protocol guarantees the generation and maintenance of a stable epileptiform pattern that faithfully reproduces the electrophysiological features observed with conventional field potential recording, persists for several hours, and outlasts sustained electrical stimulation for prolonged epochs. Tissue viability throughout the experiment is achieved thanks to the use of a small-volume custom recording chamber allowing for laminar flow and quick solution exchange even at low (1 mL/min) perfusion rates. Quick MEA mapping for real-time monitoring and selection of stimulating electrodes is performed by a custom graphic user interface (GUI).

Optimization of multifocal transcranial current stimulation for weighted cortical pattern targeting from realistic modeling of electric fields

PubMed Central

Ruffini, Giulio; Fox, Michael D.; Ripolles, Oscar; Miranda, Pedro Cavaleiro; Pascual-Leone, Alvaro

2014-01-01

Recently, multifocal transcranial current stimulation (tCS) devices using several relatively small electrodes have been used to achieve more focal stimulation of specific cortical targets. However, it is becoming increasingly recognized that many behavioral manifestations of neurological and psychiatric disease are not solely the result of abnormality in one isolated brain region but represent alterations in brain networks. In this paper we describe a method for optimizing the configuration of multifocal tCS for stimulation of brain networks, represented by spatially extended cortical targets. We show how, based on fMRI, PET, EEG or other data specifying a target map on the cortical surface for excitatory, inhibitory or neutral stimulation and a constraint of the maximal number of electrodes, a solution can be produced with the optimal currents and locations of the electrodes. The method described here relies on a fast calculation of multifocal tCS electric fields (including components normal and tangential to the cortical boundaries) using a five layer finite element model of a realistic head. Based on the hypothesis that the effects of current stimulation are to first order due to the interaction of electric fields with populations of elongated cortical neurons, it is argued that the optimization problem for tCS stimulation can be defined in terms of the component of the electric field normal to the cortical surface. Solutions are found using constrained least squares to optimize current intensities, while electrode number and their locations are selected using a genetic algorithm. For direct current tCS (tDCS) applications, we provide some examples of this technique using an available tCS system providing 8 small Ag/AgCl stimulation electrodes. We demonstrate the approach both for localized and spatially extended targets defined using rs-fcMRI and PET data, with clinical applications in stroke and depression. Finally, we extend these ideas to more general stimulation protocols, such as alternating current tCS (tACS). PMID:24345389

Effect of electrical stimulation therapy on upper extremity functional recovery and cerebral cortical changes in patients with chronic hemiplegia.

PubMed

Sasaki, Kana; Matsunaga, Toshiki; Tomite, Takenori; Yoshikawa, Takayuki; Shimada, Yoichi

2012-04-01

Hemiplegia is a common sequel of stroke and assisted living care is needed in many cases. The purpose of this study was to evaluate the effect of using surface electrode stimulation device in rehabilitation, in terms of functional improvement in upper limb and the changes in brain activation related to central nervous system reconstruction. Five patients with chronic hemiplegia received electrical stimulation therapy using the orthosis-type surface electrode stimulation device for 12 weeks. Training time was 30 min/day for the first weeks, and increased 30 min/day in every 4 weeks. Upper limb outcome measures included Brunnstrom stage, range of motion, Fugl-Meyer assessment and manual function test. Brain activation was measured using functional MRI. After therapy with therapeutic electrical stimulation (TES) for 12 weeks upper limb function improved in all cases. The results of brain activation showed two patterns. In the first, the stimulation produced an activity in the bilateral somatosensory cortices (SMC), which was seen to continue over time. The second, activation was bilateral and extensive before stimulation, but localized to the SMC after intervention. Treatment with TES using an orthosis-type electrode stimulation device improves upper limb function in chronic hemiplegia patients. The present findings suggest that there are not only efferent but also afferent effects that may promote central nervous system remodeling.

Novel bifunctional cap for simultaneous electroencephalography and transcranial electrical stimulation.

PubMed

Wunder, Sophia; Hunold, Alexander; Fiedler, Patrique; Schlegelmilch, Falk; Schellhorn, Klaus; Haueisen, Jens

2018-05-08

Neuromodulation induced by transcranial electric stimulation (TES) exhibited promising potential for clinical practice. However, the underlying mechanisms remain subject of research. The combination of TES and electroencephalography (EEG) offers great potential for investigating these mechanisms and brain function in general, especially when performed simultaneously. In conventional applications, the combination of EEG and TES suffers from limitations on the electrode level (gel for electrode-skin interface) and the usability level (preparation time, reproducibility of positioning). To overcome these limitations, we designed a bifunctional cap for simultaneous TES-EEG applications. We used novel electrode materials, namely textile stimulation electrodes and dry EEG electrodes integrated in a flexible textile cap. We verified the functionality of this cap by analysing the effect of TES on visual evoked potentials (VEPs). In accordance with previous reports using standard TES, the amplitude of the N75 component was significantly decreased post-stimulation, indicating the feasibility of using this novel flexible cap for simultaneous TES and EEG. Further, we found a significant reduction of the P100 component only during TES, indicating a different brain modulation effect during and after TES. In conclusion, the novel bifunctional cap offers a novel tool for simultaneous TES-EEG applications in clinical research, therapy monitoring and closed-loop stimulation.

Optimizing a Rodent Model of Parkinson's Disease for Exploring the Effects and Mechanisms of Deep Brain Stimulation

PubMed Central

Nowak, Karl; Mix, Eilhard; Gimsa, Jan; Strauss, Ulf; Sriperumbudur, Kiran Kumar; Benecke, Reiner; Gimsa, Ulrike

2011-01-01

Deep brain stimulation (DBS) has become a treatment for a growing number of neurological and psychiatric disorders, especially for therapy-refractory Parkinson's disease (PD). However, not all of the symptoms of PD are sufficiently improved in all patients, and side effects may occur. Further progress depends on a deeper insight into the mechanisms of action of DBS in the context of disturbed brain circuits. For this, optimized animal models have to be developed. We review not only charge transfer mechanisms at the electrode/tissue interface and strategies to increase the stimulation's energy-efficiency but also the electrochemical, electrophysiological, biochemical and functional effects of DBS. We introduce a hemi-Parkinsonian rat model for long-term experiments with chronically instrumented rats carrying a backpack stimulator and implanted platinum/iridium electrodes. This model is suitable for (1) elucidating the electrochemical processes at the electrode/tissue interface, (2) analyzing the molecular, cellular and behavioral stimulation effects, (3) testing new target regions for DBS, (4) screening for potential neuroprotective DBS effects, and (5) improving the efficacy and safety of the method. An outlook is given on further developments of experimental DBS, including the use of transgenic animals and the testing of closed-loop systems for the direct on-demand application of electric stimulation. PMID:21603182

Flexible Neural Electrode Array Based-on Porous Graphene for Cortical Microstimulation and Sensing

NASA Astrophysics Data System (ADS)

Lu, Yichen; Lyu, Hongming; Richardson, Andrew G.; Lucas, Timothy H.; Kuzum, Duygu

2016-09-01

Neural sensing and stimulation have been the backbone of neuroscience research, brain-machine interfaces and clinical neuromodulation therapies for decades. To-date, most of the neural stimulation systems have relied on sharp metal microelectrodes with poor electrochemical properties that induce extensive damage to the tissue and significantly degrade the long-term stability of implantable systems. Here, we demonstrate a flexible cortical microelectrode array based on porous graphene, which is capable of efficient electrophysiological sensing and stimulation from the brain surface, without penetrating into the tissue. Porous graphene electrodes show superior impedance and charge injection characteristics making them ideal for high efficiency cortical sensing and stimulation. They exhibit no physical delamination or degradation even after 1 million biphasic stimulation cycles, confirming high endurance. In in vivo experiments with rodents, same array is used to sense brain activity patterns with high spatio-temporal resolution and to control leg muscles with high-precision electrical stimulation from the cortical surface. Flexible porous graphene array offers a minimally invasive but high efficiency neuromodulation scheme with potential applications in cortical mapping, brain-computer interfaces, treatment of neurological disorders, where high resolution and simultaneous recording and stimulation of neural activity are crucial.

Current steering to activate targeted neural pathways during deep brain stimulation of the subthalamic region

PubMed Central

Chaturvedi, Ashutosh; Foutz, Thomas J.; McIntyre, Cameron C.

2012-01-01

Deep brain stimulation (DBS) has steadily evolved into an established surgical therapy for numerous neurological disorders, most notably Parkinson’s disease (PD). Traditional DBS technology relies on voltage-controlled stimulation with a single source; however, recent engineering advances are providing current-controlled devices with multiple independent sources. These new stimulators deliver constant current to the brain tissue, irrespective of impedance changes that occur around the electrode, and enable more specific steering of current towards targeted regions of interest. In this study, we examined the impact of current steering between multiple electrode contacts to directly activate three distinct neural populations in the subthalamic region commonly stimulated for the treatment of PD: projection neurons of the subthalamic nucleus (STN), globus pallidus internus (GPi) fibers of the lenticular fasiculus, and internal capsule (IC) fibers of passage. We used three-dimensional finite element electric field models, along with detailed multi-compartment cable models of the three neural populations to determine their activations using a wide range of stimulation parameter settings. Our results indicate that selective activation of neural populations largely depends on the location of the active electrode(s). Greater activation of the GPi and STN populations (without activating any side-effect related IC fibers) was achieved by current steering with multiple independent sources, compared to a single current source. Despite this potential advantage, it remains to be seen if these theoretical predictions result in a measurable clinical effect that outweighs the added complexity of the expanded stimulation parameter search space generated by the more flexible technology. PMID:22277548

Fractal Interfaces for Stimulating and Recording Neural Implants

NASA Astrophysics Data System (ADS)

Watterson, William James

From investigating movement in an insect to deciphering cognition in a human brain to treating Parkinson's disease, hearing loss, or even blindness, electronic implants are an essential tool for understanding the brain and treating neural diseases. Currently, the stimulating and recording resolution of these implants remains low. For instance, they can record all the neuron activity associated with movement in an insect, but are quite far from recording, at an individual neuron resolution, the large volumes of brain tissue associated with cognition. Likewise, there is remarkable success in the cochlear implant restoring hearing due to the relatively simple anatomy of the auditory nerves, but are failing to restore vision to the blind due to poor signal fidelity and transmission in stimulating the more complex anatomy of the visual nerves. The critically important research needed to improve the resolution of these implants is to optimize the neuron-electrode interface. This thesis explores geometrical and material modifications to both stimulating and recording electrodes which can improve the neuron-electrode interface. First, we introduce a fractal electrode geometry which radically improves the restored visual acuity achieved by retinal implants and leads to safe, long-term operation of the implant. Next, we demonstrate excellent neuron survival and neurite outgrowth on carbon nanotube electrodes, thus providing a safe biomaterial which forms a strong connection between the electrode and neurons. Additional preliminary evidence suggests carbon nanotubes patterned into a fractal geometry will provide further benefits in improving the electrode-neuron interface. Finally, we propose a novel implant based off field effect transistor technology which utilizes an interconnecting fractal network of semiconducting carbon nanotubes to record from thousands of neurons simutaneously at an individual neuron resolution. Taken together, these improvements have the potential to radically improve our understanding of the brain and our ability to restore function to patients of neural diseases.

Evidence of transcranial direct current stimulation-generated electric fields at subthalamic level in human brain in vivo.

PubMed

Chhatbar, Pratik Y; Kautz, Steven A; Takacs, Istvan; Rowland, Nathan C; Revuelta, Gonzalo J; George, Mark S; Bikson, Marom; Feng, Wuwei

2018-03-13

Transcranial direct current stimulation (tDCS) is a promising brain modulation technique for several disease conditions. With this technique, some portion of the current penetrates through the scalp to the cortex and modulates cortical excitability, but a recent human cadaver study questions the amount. This insufficient intracerebral penetration of currents may partially explain the inconsistent and mixed results in tDCS studies to date. Experimental validation of a transcranial alternating current stimulation-generated electric field (EF) in vivo has been performed on the cortical (using electrocorticography, ECoG, electrodes), subcortical (using stereo electroencephalography, SEEG, electrodes) and deeper thalamic/subthalamic levels (using DBS electrodes). However, tDCS-generated EF measurements have never been attempted. We aimed to demonstrate that tDCS generates biologically relevant EF as deep as the subthalamic level in vivo. Patients with movement disorders who have implanted deep brain stimulation (DBS) electrodes serve as a natural experimental model for thalamic/subthalamic recordings of tDCS-generated EF. We measured voltage changes from DBS electrodes and body resistance from tDCS electrodes in three subjects while applying direct current to the scalp at 2 mA and 4 mA over two tDCS montages. Voltage changes at the level of deep nuclei changed proportionally with the level of applied current and varied with different tDCS montages. Our findings suggest that scalp-applied tDCS generates biologically relevant EF. Incorporation of these experimental results may improve finite element analysis (FEA)-based models. Copyright © 2018 Elsevier Inc. All rights reserved.

Electrical Neural Stimulation and Simultaneous in Vivo Monitoring with Transparent Graphene Electrode Arrays Implanted in GCaMP6f Mice.

PubMed

Park, Dong-Wook; Ness, Jared P; Brodnick, Sarah K; Esquibel, Corinne; Novello, Joseph; Atry, Farid; Baek, Dong-Hyun; Kim, Hyungsoo; Bong, Jihye; Swanson, Kyle I; Suminski, Aaron J; Otto, Kevin J; Pashaie, Ramin; Williams, Justin C; Ma, Zhenqiang

2018-01-23

Electrical stimulation using implantable electrodes is widely used to treat various neuronal disorders such as Parkinson's disease and epilepsy and is a widely used research tool in neuroscience studies. However, to date, devices that help better understand the mechanisms of electrical stimulation in neural tissues have been limited to opaque neural electrodes. Imaging spatiotemporal neural responses to electrical stimulation with minimal artifact could allow for various studies that are impossible with existing opaque electrodes. Here, we demonstrate electrical brain stimulation and simultaneous optical monitoring of the underlying neural tissues using carbon-based, fully transparent graphene electrodes implanted in GCaMP6f mice. Fluorescence imaging of neural activity for varying electrical stimulation parameters was conducted with minimal image artifact through transparent graphene electrodes. In addition, full-field imaging of electrical stimulation verified more efficient neural activation with cathode leading stimulation compared to anode leading stimulation. We have characterized the charge density limitation of capacitive four-layer graphene electrodes as 116.07-174.10 μC/cm 2 based on electrochemical impedance spectroscopy, cyclic voltammetry, failure bench testing, and in vivo testing. This study demonstrates the transparent ability of graphene neural electrodes and provides a method to further increase understanding and potentially improve therapeutic electrical stimulation in the central and peripheral nervous systems.

In vitro and in vivo evaluation of poly(3,4-ethylenedioxythiophene)/poly(styrene sulfonate)/dopamine-coated electrodes for dopamine delivery.

PubMed

Sui, L; Song, X J; Ren, J; Cai, W J; Ju, L H; Wang, Y; Wang, L Y; Chen, M

2014-06-01

Poly(3,4-ethylenedioxythiophene) (PEDOT) doped with poly(styrene sulfonate) (PSS) has a variety of chemical and biomedical applications. The application of PEDOT/PSS polymers in drug delivery has attracted attention. However, whether conducting polymers of PEDOT/PSS could be used for dopamine delivery has not clear. In the present study, the PEDOT/PSS coatings incorporated with dopamine were fabricated on 0.5 mm diameter platinum electrodes, electrochemical properties, and dopamine delivery capacities of these electrodes were evaluated in vitro and in vivo through implanting these electrodes into brain striatum area. The findings demonstrated that the PEDOT/PSS/dopamine coatings on platinum electrodes could reduce electrodes impedances, increase charge storage capacities, and release significant levels of dopamine upon electrical stimulation of these electrodes. These results indicated that polymers of PEDOT/PSS/dopamine could be used for dopamine delivery, implicating potential application of PEDOT/PSS/dopamine-coated implantable electrodes in the treatment of some diseases associated with dopamine deficits, such as, electrodes for the treatment of Parkinson's disease during deep brain stimulation. Copyright © 2013 Wiley Periodicals, Inc.

Utility of a tripolar stimulating electrode for eliciting dopamine release in the rat striatum.

PubMed

Bergstrom, B P; Garris, P A

1999-03-01

The present study evaluated tripolar stimulating electrodes for eliciting dopamine release in the rat brain in vivo. Stimulating electrodes were placed either in the medial forebrain bundle or in the ventral mesencephalon associated with the ventral tegmental area and substantia nigra. The concentration of extracellular dopamine was monitored in dopamine terminal fields at 100-ms intervals using fast-scan cyclic voltammetry at carbon-fiber microelectrodes. To characterize the stimulated area, recordings were collected in several striatal regions including the caudate putamen and the core and shell of the nucleus accumbens. The tripolar electrode was equally effective in stimulating dopamine release in medial and lateral regions of the striatum. In contrast, responses evoked by a bipolar electrode were typically greater in one mediolateral edge versus the other. The added size of the tripolar electrode did not appear to cause complications as signals were stable over the course of the experiment (3 h). Subsets of mesostriatal dopamine neurons could also be selectively activated using the tripolar electrode in excellent agreement with previously described topography. Taken together, these results suggested that the tripolar stimulating electrode is well suited for studying the regulation of midbrain dopamine neurons in vivo.

Long-term implantation of deep brain stimulation electrodes in the pontine micturition centre of the Göttingen minipig.

PubMed

Jensen, Kristian N; Deding, Dorthe; Sørensen, Jens Christian; Bjarkam, Carsten R

2009-07-01

To implant deep brain stimulation (DBS) electrodes in the porcine pontine micturition centre (PMC) in order to establish a large animal model of PMC-DBS. Brain stems from four Göttingen minipigs were sectioned coronally into 40-mum-thick histological sections and stained with Nissl, auto-metallographic myelin stain, tyrosine hydroxylase and corticotrophin-releasing factor immunohistochemistry in order to identify the porcine PMC. DBS electrodes were then stereotaxically implanted on the right side into the PMC in four Göttingen minipigs, and the bladder response to electrical stimulation was evaluated by subsequent cystometry performed immediately after the operation and several weeks later. A paired CRF-dense area homologous to the PMC in other species was encountered in the rostral pontine tegmentum medial to the locus coeruleus and ventral to the floor of the fourth ventricle. Electrical stimulation of the CRF-dense area resulted in an increased detrusor pressure followed by visible voiding in some instances. The pigs were allowed to survive between 14 and 55 days, and electrical stimulation resulting in an increased detrusor pressure was performed on more than one occasion without affecting consciousness or general thriving. None of the pigs developed postoperative infections or died prematurely. DBS electrodes can be implanted for several weeks in the identified CRF-dense area resulting in a useful large animal model for basic research on micturition and the future clinical use of this treatment modality in neurogenic supra-pontine voiding disorders.

Mechanisms and targets of deep brain stimulation in movement disorders.

PubMed

Johnson, Matthew D; Miocinovic, Svjetlana; McIntyre, Cameron C; Vitek, Jerrold L

2008-04-01

Chronic electrical stimulation of the brain, known as deep brain stimulation (DBS), has become a preferred surgical treatment for medication-refractory movement disorders. Despite its remarkable clinical success, the therapeutic mechanisms of DBS are still not completely understood, limiting opportunities to improve treatment efficacy and simplify selection of stimulation parameters. This review addresses three questions essential to understanding the mechanisms of DBS. 1) How does DBS affect neuronal tissue in the vicinity of the active electrode or electrodes? 2) How do these changes translate into therapeutic benefit on motor symptoms? 3) How do these effects depend on the particular site of stimulation? Early hypotheses proposed that stimulation inhibited neuronal activity at the site of stimulation, mimicking the outcome of ablative surgeries. Recent studies have challenged that view, suggesting that although somatic activity near the DBS electrode may exhibit substantial inhibition or complex modulation patterns, the output from the stimulated nucleus follows the DBS pulse train by direct axonal excitation. The intrinsic activity is thus replaced by high-frequency activity that is time-locked to the stimulus and more regular in pattern. These changes in firing pattern are thought to prevent transmission of pathologic bursting and oscillatory activity, resulting in the reduction of disease symptoms through compensatory processing of sensorimotor information. Although promising, this theory does not entirely explain why DBS improves motor symptoms at different latencies. Understanding these processes on a physiological level will be critically important if we are to reach the full potential of this powerful tool.

Probing the Human Brain with Stimulating Electrodes: The Story of Roberts Bartholow's (1874) Experiment on Mary Rafferty

ERIC Educational Resources Information Center

Harris, Lauren Julius; Almerigi, Jason B.

2009-01-01

Roberts Bartholow's 1874 experiment on Mary Rafferty is widely cited as the first demonstration, by direct application of stimulating electrodes, of the motor excitability of the human cerebral cortex. The many accounts of the experiment, however, leave certain questions and details unexamined or unresolved, especially about Bartholow's goals, the…

Optimized multi-electrode stimulation increases focality and intensity at target

NASA Astrophysics Data System (ADS)

Dmochowski, Jacek P.; Datta, Abhishek; Bikson, Marom; Su, Yuzhuo; Parra, Lucas C.

2011-08-01

Transcranial direct current stimulation (tDCS) provides a non-invasive tool to elicit neuromodulation by delivering current through electrodes placed on the scalp. The present clinical paradigm uses two relatively large electrodes to inject current through the head resulting in electric fields that are broadly distributed over large regions of the brain. In this paper, we present a method that uses multiple small electrodes (i.e. 1.2 cm diameter) and systematically optimize the applied currents to achieve effective and targeted stimulation while ensuring safety of stimulation. We found a fundamental trade-off between achievable intensity (at the target) and focality, and algorithms to optimize both measures are presented. When compared with large pad-electrodes (approximated here by a set of small electrodes covering 25cm2), the proposed approach achieves electric fields which exhibit simultaneously greater focality (80% improvement) and higher target intensity (98% improvement) at cortical targets using the same total current applied. These improvements illustrate the previously unrecognized and non-trivial dependence of the optimal electrode configuration on the desired electric field orientation and the maximum total current (due to safety). Similarly, by exploiting idiosyncratic details of brain anatomy, the optimization approach significantly improves upon prior un-optimized approaches using small electrodes. The analysis also reveals the optimal use of conventional bipolar montages: maximally intense tangential fields are attained with the two electrodes placed at a considerable distance from the target along the direction of the desired field; when radial fields are desired, the maximum-intensity configuration consists of an electrode placed directly over the target with a distant return electrode. To summarize, if a target location and stimulation orientation can be defined by the clinician, then the proposed technique is superior in terms of both focality and intensity as compared to previous solutions and is thus expected to translate into improved patient safety and increased clinical efficacy.

Electroencephalography: Subdural Multi-Electrode Brain Chip.

DTIC Science & Technology

1995-12-01

showing a blind subject reading Braille letters that had been inserted into his visual cortex by stimulating appropriate sets of electrodes. The...subject in Dobelle’s experiment 50 had been blind for 10 years and was able to read Braille at 30 letters a minute using a 64 electrode array for...Evans, "’ Braille ’ Reading by a Blind Volunteer by Visual cortex Stimulation," Nature, 259: 111-112 (January 1976). A.K. Engel, et al. "Temporal Coding

Induction of panic attack by stimulation of the ventromedial hypothalamus.

PubMed

Wilent, W Bryan; Oh, Michael Y; Buetefisch, Cathrin M; Bailes, Julian E; Cantella, Diane; Angle, Cindy; Whiting, Donald M

2010-06-01

Panic attacks are sudden debilitating attacks of intense distress often accompanied by physical symptoms such as shortness of breath and heart palpitations. Numerous brain regions, hormones, and neurotransmitter systems are putatively involved, but the etiology and neurocircuitry of panic attacks is far from established. One particular brain region of interest is the ventromedial hypothalamus (VMH). In cats and rats, electrical stimulation delivered to the VMH has been shown to evoke an emotional "panic attack-like" escape behavior, and in humans, stimulation targeting nuclei just posterior or anterior to the VMH has reportedly induced panic attacks. The authors report findings obtained in an awake patient undergoing bilateral implantation of deep brain stimulation electrodes into the hypothalamus that strongly implicates the VMH as being critically involved in the genesis of panic attacks. First, as the stimulating electrode progressed deeper into the VMH, the intensity of stimulation required to evoke an attack systematically decreased; second, while stimulation of the VMH in either hemisphere evoked panic, stimulation that appeared to be in the center of the VMH was more potent. Thus, this evidence supports the role of the VMH in the induction of panic attacks purported by animal studies.

Differential effects of deep brain stimulation on verbal fluency.

PubMed

Ehlen, Felicitas; Schoenecker, Thomas; Kühn, Andrea A; Klostermann, Fabian

2014-07-01

We aimed at gaining insights into principles of subcortical lexical processing. Therefore, effects of deep brain stimulation (DBS) in different target structures on verbal fluency (VF) were tested. VF was assessed with active vs. inactivated DBS in 13 and 14 patients with DBS in the vicinity of the thalamic ventral intermediate nucleus (VIM) and, respectively, of the subthalamic nucleus (STN). Results were correlated to electrode localizations in postoperative MRI, and compared to those of 12 age-matched healthy controls. Patients' VF performance was generally below normal. However, while activation of DBS in the vicinity of VIM provoked marked VF decline, it induced subtle phonemic VF enhancement in the vicinity of STN. The effects correlated with electrode localizations in left hemispheric stimulation sites. The results show distinct dependencies of VF on DBS in the vicinity of VIM vs. STN. Particular risks for deterioration occur in patients with relatively ventromedial thalamic electrodes. Copyright © 2014 Elsevier Inc. All rights reserved.

Individual differences in transcranial electrical stimulation current density

PubMed Central

Russell, Michael J; Goodman, Theodore; Pierson, Ronald; Shepherd, Shane; Wang, Qiang; Groshong, Bennett; Wiley, David F

2013-01-01

Transcranial electrical stimulation (TCES) is effective in treating many conditions, but it has not been possible to accurately forecast current density within the complex anatomy of a given subject's head. We sought to predict and verify TCES current densities and determine the variability of these current distributions in patient-specific models based on magnetic resonance imaging (MRI) data. Two experiments were performed. The first experiment estimated conductivity from MRIs and compared the current density results against actual measurements from the scalp surface of 3 subjects. In the second experiment, virtual electrodes were placed on the scalps of 18 subjects to model simulated current densities with 2 mA of virtually applied stimulation. This procedure was repeated for 4 electrode locations. Current densities were then calculated for 75 brain regions. Comparison of modeled and measured external current in experiment 1 yielded a correlation of r = .93. In experiment 2, modeled individual differences were greatest near the electrodes (ten-fold differences were common), but simulated current was found in all regions of the brain. Sites that were distant from the electrodes (e.g. hypothalamus) typically showed two-fold individual differences. MRI-based modeling can effectively predict current densities in individual brains. Significant variation occurs between subjects with the same applied electrode configuration. Individualized MRI-based modeling should be considered in place of the 10-20 system when accurate TCES is needed. PMID:24285948

Optimization of multifocal transcranial current stimulation for weighted cortical pattern targeting from realistic modeling of electric fields.

PubMed

Ruffini, Giulio; Fox, Michael D; Ripolles, Oscar; Miranda, Pedro Cavaleiro; Pascual-Leone, Alvaro

2014-04-01

Recently, multifocal transcranial current stimulation (tCS) devices using several relatively small electrodes have been used to achieve more focal stimulation of specific cortical targets. However, it is becoming increasingly recognized that many behavioral manifestations of neurological and psychiatric disease are not solely the result of abnormality in one isolated brain region but represent alterations in brain networks. In this paper we describe a method for optimizing the configuration of multifocal tCS for stimulation of brain networks, represented by spatially extended cortical targets. We show how, based on fMRI, PET, EEG or other data specifying a target map on the cortical surface for excitatory, inhibitory or neutral stimulation and a constraint on the maximal number of electrodes, a solution can be produced with the optimal currents and locations of the electrodes. The method described here relies on a fast calculation of multifocal tCS electric fields (including components normal and tangential to the cortical boundaries) using a five layer finite element model of a realistic head. Based on the hypothesis that the effects of current stimulation are to first order due to the interaction of electric fields with populations of elongated cortical neurons, it is argued that the optimization problem for tCS stimulation can be defined in terms of the component of the electric field normal to the cortical surface. Solutions are found using constrained least squares to optimize current intensities, while electrode number and their locations are selected using a genetic algorithm. For direct current tCS (tDCS) applications, we provide some examples of this technique using an available tCS system providing 8 small Ag/AgCl stimulation electrodes. We demonstrate the approach both for localized and spatially extended targets defined using rs-fcMRI and PET data, with clinical applications in stroke and depression. Finally, we extend these ideas to more general stimulation protocols, such as alternating current tCS (tACS). Copyright © 2013 Elsevier Inc. All rights reserved.

Computationally optimized ECoG stimulation with local safety constraints.

PubMed

Guler, Seyhmus; Dannhauer, Moritz; Roig-Solvas, Biel; Gkogkidis, Alexis; Macleod, Rob; Ball, Tonio; Ojemann, Jeffrey G; Brooks, Dana H

2018-06-01

Direct stimulation of the cortical surface is used clinically for cortical mapping and modulation of local activity. Future applications of cortical modulation and brain-computer interfaces may also use cortical stimulation methods. One common method to deliver current is through electrocorticography (ECoG) stimulation in which a dense array of electrodes are placed subdurally or epidurally to stimulate the cortex. However, proximity to cortical tissue limits the amount of current that can be delivered safely. It may be desirable to deliver higher current to a specific local region of interest (ROI) while limiting current to other local areas more stringently than is guaranteed by global safety limits. Two commonly used global safety constraints bound the total injected current and individual electrode currents. However, these two sets of constraints may not be sufficient to prevent high current density locally (hot-spots). In this work, we propose an efficient approach that prevents current density hot-spots in the entire brain while optimizing ECoG stimulus patterns for targeted stimulation. Specifically, we maximize the current along a particular desired directional field in the ROI while respecting three safety constraints: one on the total injected current, one on individual electrode currents, and the third on the local current density magnitude in the brain. This third set of constraints creates a computational barrier due to the huge number of constraints needed to bound the current density at every point in the entire brain. We overcome this barrier by adopting an efficient two-step approach. In the first step, the proposed method identifies the safe brain region, which cannot contain any hot-spots solely based on the global bounds on total injected current and individual electrode currents. In the second step, the proposed algorithm iteratively adjusts the stimulus pattern to arrive at a solution that exhibits no hot-spots in the remaining brain. We report on simulations on a realistic finite element (FE) head model with five anatomical ROIs and two desired directional fields. We also report on the effect of ROI depth and desired directional field on the focality of the stimulation. Finally, we provide an analysis of optimization runtime as a function of different safety and modeling parameters. Our results suggest that optimized stimulus patterns tend to differ from those used in clinical practice. Copyright © 2018 Elsevier Inc. All rights reserved.

What is the optimal anodal electrode position for inducing corticomotor excitability changes in transcranial direct current stimulation?

PubMed

Lee, Minji; Kim, Yun-Hee; Im, Chang-Hwan; Kim, Jung-Hoon; Park, Chang-hyun; Chang, Won Hyuk; Lee, Ahee

2015-01-01

Transcranial direct current stimulation (tDCS) non-invasively modulates brain function by inducing neuronal excitability. The conventional hot spot for inducing the highest current density in the hand motor area may not be the optimal site for effective stimulation. In this study, we investigated the influence of the center position of the anodal electrode on changes in motor cortical excitability. We considered three tDCS conditions in 16 healthy subjects: (i) real stimulation with the anodal electrode located at the conventional hand motor hot spot determined by motor evoked potentials (MEPs); (ii) real stimulation with the anodal electrode located at the point with the highest current density in the hand motor area as determined by electric current simulation; and (iii) sham stimulation. Motor cortical excitability as measured by MEP amplitude increased after both real stimulation conditions, but not after sham stimulation. Stimulation using the simulation-derived anodal electrode position, which was found to be posterior to the MEP hot spot for all subjects, induced higher motor cortical excitability. Individual positioning of the anodal electrode, based on the consideration of anatomical differences between subjects, appears to be important for maximizing the effects of tDCS. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Mirth and laughter elicited during brain stimulation.

PubMed

Fernández-Baca Vaca, Guadalupe; Lüders, Hans O; Basha, Maysaa Merhi; Miller, Jonathan P

2011-12-01

There are few reports of laughter and/or mirth evoked by electrical stimulation of the brain. In this study, we present a patient with intractable epilepsy in whom mirth and laughter was consistently produced during stimulation of the left inferior frontal gyrus (opercular part) using stereotactically placed depth electrodes. A review of the literature shows that cortical sites that produce mirth when stimulated are located in the dominant hemisphere close to language areas or cortical negative motor areas.

Complications of deep brain stimulation: a collective review.

PubMed

Chan, Danny T M; Zhu, Xian Lun; Yeung, Jonas H M; Mok, Vincent C T; Wong, Edith; Lau, Clara; Wong, Rosanna; Lau, Christine; Poon, Wai S

2009-10-01

Since the first deep brain stimulation (DBS) performed for movement disorder more than a decade ago, DBS has become a standard operation for advanced Parkinson's disease. Its indications are expanding to areas of dystonia, psychiatric conditions and refractory epilepsy. Additionally, a new set of DBS-related complications have arisen. Many teams found a slow learning curve from this complication-prone operation. We would like to investigate complications arising from 100 DBS electrode insertions and its prevention. We performed an audit in all DBS patients for operation-related complications in our centre from 1997 to 2008. Complications were classified into operation-related, hardware-related and stimulation-related. Operation-related complications included intracranial haemorrhages and electrode malposition. Hardware-related complications included fracture of electrodes, electrode migration, infection and erosion. Stimulation-related complications included sensorimotor conditions, psychiatric conditions and life-threatening conditions. From 1997 to the end of 2008, 100 DBS electrodes were inserted in 55 patients for movement disorders, mostly for Parkinsons disease (50 patients). There was one symptomatic cerebral haemorrhage (1%) and two electrode malpositions (2%). Meticulous surgical planning, use of microdriver and a reliable electrode anchorage device would minimise this group of complications. There were two electrode fractures, one electrode migration and one pulse-generator infection which contributed to the hardware-related complication rate of 5%. There were no sensorimotor or life-threatening complications in our group. However, three patients suffered from reversible psychiatric symptoms after DBS. DBS is, on the one hand, an effective surgical treatment for movement disorders. On the other hand, it is a complication-prone operation. A dedicated "Movement Disorder Team" consisting of neurologists, neurophysiologists, functional neurosurgeons, neuropsychologists and nursing specialists is essential. Liaison among team members in peri-operative periods and postoperative care is the key to avoiding complications and having a successful patient outcome.

External trial deep brain stimulation device for the application of desynchronizing stimulation techniques.

PubMed

Hauptmann, C; Roulet, J-C; Niederhauser, J J; Döll, W; Kirlangic, M E; Lysyansky, B; Krachkovskyi, V; Bhatti, M A; Barnikol, U B; Sasse, L; Bührle, C P; Speckmann, E-J; Götz, M; Sturm, V; Freund, H-J; Schnell, U; Tass, P A

2009-12-01

In the past decade deep brain stimulation (DBS)-the application of electrical stimulation to specific target structures via implanted depth electrodes-has become the standard treatment for medically refractory Parkinson's disease and essential tremor. These diseases are characterized by pathological synchronized neuronal activity in particular brain areas. We present an external trial DBS device capable of administering effectively desynchronizing stimulation techniques developed with methods from nonlinear dynamics and statistical physics according to a model-based approach. These techniques exploit either stochastic phase resetting principles or complex delayed-feedback mechanisms. We explain how these methods are implemented into a safe and user-friendly device.

Deep brain stimulation can regulate arterial blood pressure in awake humans.

PubMed

Green, Alexander L; Wang, Shouyan; Owen, Sarah L F; Xie, Kangning; Liu, Xuguang; Paterson, David J; Stein, John F; Bain, Peter G; Aziz, Tipu Z

2005-11-07

The periaqueductal grey matter is known to play a role in cardiovascular control in animals. Cardiovascular responses to electrical stimulation of the periventricular/periaqueductal grey matter were measured in 15 awake human study participants following implantation of deep brain stimulating electrodes for treatment of chronic pain. We found that stimulation of the ventral periventricular/periaqueductal grey matter caused a mean reduction in systolic blood pressure of 14.2+/-3.6 mmHg in seven patients and stimulation of the dorsal periventricular/periaqueductal grey matter caused a mean increase of 16.7+/-5.9 mmHg in six patients. A comparison between ventral and dorsal electrodes demonstrated significant differences (P<0.05). These changes were accompanied by analogous changes in diastolic blood pressure, pulse pressure, maximum dP/dt but not in the time interval between each R wave on the electrocardiogram.

PET Mapping for Brain-Computer Interface Stimulation of the Ventroposterior Medial Nucleus of the Thalamus in Rats with Implanted Electrodes.

PubMed

Zhu, Yunqi; Xu, Kedi; Xu, Caiyun; Zhang, Jiacheng; Ji, Jianfeng; Zheng, Xiaoxiang; Zhang, Hong; Tian, Mei

2016-07-01

Brain-computer interface (BCI) technology has great potential for improving the quality of life for neurologic patients. This study aimed to use PET mapping for BCI-based stimulation in a rat model with electrodes implanted in the ventroposterior medial (VPM) nucleus of the thalamus. PET imaging studies were conducted before and after stimulation of the right VPM. Stimulation induced significant orienting performance. (18)F-FDG uptake increased significantly in the paraventricular thalamic nucleus, septohippocampal nucleus, olfactory bulb, left crus II of the ansiform lobule of the cerebellum, and bilaterally in the lateral septum, amygdala, piriform cortex, endopiriform nucleus, and insular cortex, but it decreased in the right secondary visual cortex, right simple lobule of the cerebellum, and bilaterally in the somatosensory cortex. This study demonstrated that PET mapping after VPM stimulation can identify specific brain regions associated with orienting performance. PET molecular imaging may be an important approach for BCI-based research and its clinical applications. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

SPECT-imaging of activity-dependent changes in regional cerebral blood flow induced by electrical and optogenetic self-stimulation in mice.

PubMed

Kolodziej, Angela; Lippert, Michael; Angenstein, Frank; Neubert, Jenni; Pethe, Annette; Grosser, Oliver S; Amthauer, Holger; Schroeder, Ulrich H; Reymann, Klaus G; Scheich, Henning; Ohl, Frank W; Goldschmidt, Jürgen

2014-12-01

Electrical and optogenetic methods for brain stimulation are widely used in rodents for manipulating behavior and analyzing functional connectivities in neuronal circuits. High-resolution in vivo imaging of the global, brain-wide, activation patterns induced by these stimulations has remained challenging, in particular in awake behaving mice. We here mapped brain activation patterns in awake, intracranially self-stimulating mice using a novel protocol for single-photon emission computed tomography (SPECT) imaging of regional cerebral blood flow (rCBF). Mice were implanted with either electrodes for electrical stimulation of the medial forebrain bundle (mfb-microstim) or with optical fibers for blue-light stimulation of channelrhodopsin-2 expressing neurons in the ventral tegmental area (vta-optostim). After training for self-stimulation by current or light application, respectively, mice were implanted with jugular vein catheters and intravenously injected with the flow tracer 99m-technetium hexamethylpropyleneamine oxime (99mTc-HMPAO) during seven to ten minutes of intracranial self-stimulation or ongoing behavior without stimulation. The 99mTc-brain distributions were mapped in anesthetized animals after stimulation using multipinhole SPECT. Upon self-stimulation rCBF strongly increased at the electrode tip in mfb-microstim mice. In vta-optostim mice peak activations were found outside the stimulation site. Partly overlapping brain-wide networks of activations and deactivations were found in both groups. When testing all self-stimulating mice against all controls highly significant activations were found in the rostromedial nucleus accumbens shell. SPECT-imaging of rCBF using intravenous tracer-injection during ongoing behavior is a new tool for imaging regional brain activation patterns in awake behaving rodents providing higher spatial and temporal resolutions than 18F-2-fluoro-2-dexoyglucose positron emission tomography. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Flexible, foldable, actively multiplexed, high-density electrode array for mapping brain activity in vivo.

PubMed

Viventi, Jonathan; Kim, Dae-Hyeong; Vigeland, Leif; Frechette, Eric S; Blanco, Justin A; Kim, Yun-Soung; Avrin, Andrew E; Tiruvadi, Vineet R; Hwang, Suk-Won; Vanleer, Ann C; Wulsin, Drausin F; Davis, Kathryn; Gelber, Casey E; Palmer, Larry; Van der Spiegel, Jan; Wu, Jian; Xiao, Jianliang; Huang, Yonggang; Contreras, Diego; Rogers, John A; Litt, Brian

2011-11-13

Arrays of electrodes for recording and stimulating the brain are used throughout clinical medicine and basic neuroscience research, yet are unable to sample large areas of the brain while maintaining high spatial resolution because of the need to individually wire each passive sensor at the electrode-tissue interface. To overcome this constraint, we developed new devices that integrate ultrathin and flexible silicon nanomembrane transistors into the electrode array, enabling new dense arrays of thousands of amplified and multiplexed sensors that are connected using fewer wires. We used this system to record spatial properties of cat brain activity in vivo, including sleep spindles, single-trial visual evoked responses and electrographic seizures. We found that seizures may manifest as recurrent spiral waves that propagate in the neocortex. The developments reported here herald a new generation of diagnostic and therapeutic brain-machine interface devices.

Individualized model predicts brain current flow during transcranial direct-current stimulation treatment in responsive stroke patient.

PubMed

Datta, Abhishek; Baker, Julie M; Bikson, Marom; Fridriksson, Julius

2011-07-01

Although numerous published reports have demonstrated the beneficial effects of transcranial direct-current stimulation (tDCS) on task performance, fundamental questions remain regarding the optimal electrode configuration on the scalp. Moreover, it is expected that lesioned brain tissue will influence current flow and should therefore be considered (and perhaps leveraged) in the design of individualized tDCS therapies for stroke. The current report demonstrates how different electrode configurations influence the flow of electrical current through brain tissue in a patient who responded positively to a tDCS treatment targeting aphasia. The patient, a 60-year-old man, sustained a left hemisphere ischemic stroke (lesion size = 87.42 mL) 64 months before his participation. In this study, we present results from the first high-resolution (1 mm(3)) model of tDCS in a brain with considerable stroke-related damage; the model was individualized for the patient who received anodal tDCS to his left frontal cortex with the reference cathode electrode placed on his right shoulder. We modeled the resulting brain current flow and also considered three additional reference electrode positions: right mastoid, right orbitofrontal cortex, and a "mirror" configuration with the anode over the undamaged right cortex. Our results demonstrate the profound effect of lesioned tissue on resulting current flow and the ability to modulate current pattern through the brain, including perilesional regions, through electrode montage design. The complexity of brain current flow modulation by detailed normal and pathologic anatomy suggest: (1) That computational models are critical for the rational interpretation and design of individualized tDCS stroke-therapy; and (2) These models must accurately reproduce head anatomy as shown here. Copyright © 2011 Elsevier Inc. All rights reserved.

Combined use of transcranial magnetic stimulation and metal electrode implants: a theoretical assessment of safety considerations

NASA Astrophysics Data System (ADS)

Golestanirad, Laleh; Rouhani, Hossein; Elahi, Behzad; Shahim, Kamal; Chen, Robert; Mosig, Juan R.; Pollo, Claudio; Graham, Simon J.

2012-12-01

This paper provides a theoretical assessment of the safety considerations encountered in the simultaneous use of transcranial magnetic stimulation (TMS) and neurological interventions involving implanted metallic electrodes, such as electrocorticography. Metal implants are subject to magnetic forces due to fast alternating magnetic fields produced by the TMS coil. The question of whether the mechanical movement of the implants leads to irreversible damage of brain tissue is addressed by an electromagnetic simulation which quantifies the magnitude of imposed magnetic forces. The assessment is followed by a careful mechanical analysis determining the maximum tolerable force which does not cause irreversible tissue damage. Results of this investigation provide useful information on the range of TMS stimulator output powers which can be safely used in patients having metallic implants. It is shown that conventional TMS applications can be considered safe when applied on patients with typical electrode implants as the induced stress in the brain tissue remains well below the limit of tissue damage.

Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization

PubMed Central

Calabrese, Evan; Hickey, Patrick; Hulette, Christine; Zhang, Jingxian; Parente, Beth; Lad, Shivanand P.; Johnson, G. Allan

2015-01-01

Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved 3D reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate accurate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms. PMID:26043869

Assessing the direct effects of deep brain stimulation using embedded axon models

NASA Astrophysics Data System (ADS)

Sotiropoulos, Stamatios N.; Steinmetz, Peter N.

2007-06-01

To better understand the spatial extent of the direct effects of deep brain stimulation (DBS) on neurons, we implemented a geometrically realistic finite element electrical model incorporating anisotropic and inhomogenous conductivities. The model included the subthalamic nucleus (STN), substantia nigra (SN), zona incerta (ZI), fields of Forel H2 (FF), internal capsule (IC) and Medtronic 3387/3389 electrode. To quantify the effects of stimulation, we extended previous studies by using multi-compartment axon models with geometry and orientation consistent with anatomical features of the brain regions of interest. Simulation of axonal firing produced a map of relative changes in axonal activation. Voltage-controlled stimulation, with clinically typical parameters at the dorso-lateral STN, caused axon activation up to 4 mm from the target. This activation occurred within the FF, IC, SN and ZI with current intensities close to the average injected during DBS (3 mA). A sensitivity analysis of model parameters (fiber size, fiber orientation, degree of inhomogeneity, degree of anisotropy, electrode configuration) revealed that the FF and IC were consistently activated. Direct activation of axons outside the STN suggests that other brain regions may be involved in the beneficial effects of DBS when treating Parkinsonian symptoms.

Electric Field Comparison between Microelectrode Recording and Deep Brain Stimulation Systems—A Simulation Study

PubMed Central

Johansson, Johannes; Wårdell, Karin; Hemm, Simone

2018-01-01

The success of deep brain stimulation (DBS) relies primarily on the localization of the implanted electrode. Its final position can be chosen based on the results of intraoperative microelectrode recording (MER) and stimulation tests. The optimal position often differs from the final one selected for chronic stimulation with the DBS electrode. The aim of the study was to investigate, using finite element method (FEM) modeling and simulations, whether lead design, electrical setup, and operating modes induce differences in electric field (EF) distribution and in consequence, the clinical outcome. Finite element models of a MER system and a chronic DBS lead were developed. Simulations of the EF were performed for homogenous and patient-specific brain models to evaluate the influence of grounding (guide tube vs. stimulator case), parallel MER leads, and non-active DBS contacts. Results showed that the EF is deformed depending on the distance between the guide tube and stimulating contact. Several parallel MER leads and the presence of the non-active DBS contacts influence the EF distribution. The DBS EF volume can cover the intraoperatively produced EF, but can also extend to other anatomical areas. In conclusion, EF deformations between stimulation tests and DBS should be taken into consideration as they can alter the clinical outcome. PMID:29415442

The habenula in neurosurgery for depression: A convergence of functional neuroanatomy, psychiatry and imaging.

PubMed

Skandalakis, Georgios P; Koutsarnakis, Christos; Kalyvas, Aristotelis V; Skandalakis, Panagiotis; Johnson, Elizabeth O; Stranjalis, George

2018-05-05

The habenula is a small, mostly underrated structure in the pineal region. Multidisciplinary findings demonstrate an underlying complex connectivity of the habenula with the rest of the brain, subserving its major role in normal behavior and the pathophysiology of depression. These findings suggest the potential application of "habenular psychosurgery" in the treatment of mental disorders. The remission of two patients with treatment-resistant major depression treated with deep brain stimulation of the habenula supported the hypothesis that the habenula is an effective target for deep brain stimulation and initiated a surge of basic science research. This review aims to assess the viability of the deep brain stimulation of the habenula as a treatment option for treatment resistant depression. PubMed and the Cochrane Library databases were searched with no chronological restrictions for the identification of relevant articles. The results of this review are presented in a narrative form describing the functional neuroanatomy of the human habenula, its implications in major depression, findings of electrode implantation of this region and findings of deep brain stimulation of the habenula for the treatment of depression. Data assessing the hypothesis are scarce. Nonetheless, findings highlight the major role of the habenula in normal, as well as in pathological brain function, particularly in depression disorders. Moreover, findings of studies utilizing electrode implantation in the region of the habenula underscore our growing realization that research in neuroscience and deep brain stimulation complement each other in a reciprocal relationship; they are as self-reliant, as much as they depend on each other. Copyright © 2018. Published by Elsevier B.V.

Sensor integration of multiple tripolar concentric ring electrodes improves pentylenetetrazole-induced seizure onset detection in rats.

PubMed

Makeyev, Oleksandr; Ding, Quan; Kay, Steven M; Besio, Walter G

2012-01-01

As epilepsy affects approximately one percent of the world population, electrical stimulation of the brain has recently shown potential for additive seizure control therapy. Previously, we applied noninvasive transcranial focal stimulation via tripolar concentric ring electrodes on the scalp of rats after inducing seizures with pentylenetetrazole. We developed a system to detect seizures and automatically trigger the stimulation and evaluated the system on the electrographic activity from rats. In this preliminary study we propose and validate a novel seizure onset detection algorithm based on exponentially embedded family. Unlike the previously proposed approach it integrates the data from multiple electrodes allowing an improvement of the detector performance.

Systems for deep brain stimulation: review of technical features.

PubMed

Amon, A; Alesch, F

2017-09-01

The use of deep brain stimulation (DBS) is an important treatment option for movement disorders and other medical conditions. Today, three major manufacturers provide implantable systems for DBS. Although the underlying principle is basically the same for all available systems, the differences in the technical features vary considerably. This article outlines aspects regarding the technical features of DBS systems. The differences between voltage and current sources are addressed and their effect on stimulation is shown. To maintain clinical benefit and minimize side effects the stimulation field has to be adapted to the requirements of the patient. Shaping of the stimulation field can be achieved by the electrode design and polarity configuration. Furthermore, the electric signal consisting of stimulation rate, stimulation amplitude and pulse width affect the stimulation field. Interleaving stimulation is an additional concept, which permits improved treatment outcomes. Therefore, the electrode design, the polarity, the electric signal, and the concept of interleaving stimulation are presented. The investigated systems can be also categorized as rechargeable and non-rechargeable, which is briefly discussed. Options for interconnecting different system components from various manufacturers are presented. The present paper summarizes the technical features and their combination possibilities, which can have a major impact on the therapeutic effect.

A Stepwise Approach: Decreasing Infection in Deep Brain Stimulation for Childhood Dystonic Cerebral Palsy.

PubMed

Johans, Stephen J; Swong, Kevin N; Hofler, Ryan C; Anderson, Douglas E

2017-09-01

Dystonia is a movement disorder characterized by involuntary muscle contractions, which cause twisting movements or abnormal postures. Deep brain stimulation has been used to improve the quality of life for secondary dystonia caused by cerebral palsy. Despite being a viable treatment option for childhood dystonic cerebral palsy, deep brain stimulation is associated with a high rate of infection in children. The authors present a small series of patients with dystonic cerebral palsy who underwent a stepwise approach for bilateral globus pallidus interna deep brain stimulation placement in order to decrease the rate of infection. Four children with dystonic cerebral palsy who underwent a total of 13 surgical procedures (electrode and battery placement) were identified via a retrospective review. There were zero postoperative infections. Using a multistaged surgical plan for pediatric patients with dystonic cerebral palsy undergoing deep brain stimulation may help to reduce the risk of infection.

Transcranial direct current stimulation in obsessive-compulsive disorder: emerging clinical evidence and considerations for optimal montage of electrodes.

PubMed

Senço, Natasha M; Huang, Yu; D'Urso, Giordano; Parra, Lucas C; Bikson, Marom; Mantovani, Antonio; Shavitt, Roseli G; Hoexter, Marcelo Q; Miguel, Eurípedes C; Brunoni, André R

2015-07-01

Neuromodulation techniques for obsessive-compulsive disorder (OCD) treatment have expanded with greater understanding of the brain circuits involved. Transcranial direct current stimulation (tDCS) might be a potential new treatment for OCD, although the optimal montage is unclear. To perform a systematic review on meta-analyses of repetitive transcranianal magnetic stimulation (rTMS) and deep brain stimulation (DBS) trials for OCD, aiming to identify brain stimulation targets for future tDCS trials and to support the empirical evidence with computer head modeling analysis. Systematic reviews of rTMS and DBS trials on OCD in Pubmed/MEDLINE were searched. For the tDCS computational analysis, we employed head models with the goal of optimally targeting current delivery to structures of interest. Only three references matched our eligibility criteria. We simulated four different electrodes montages and analyzed current direction and intensity. Although DBS, rTMS and tDCS are not directly comparable and our theoretical model, based on DBS and rTMS targets, needs empirical validation, we found that the tDCS montage with the cathode over the pre-supplementary motor area and extra-cephalic anode seems to activate most of the areas related to OCD.

An Automated Method for High-Definition Transcranial Direct Current Stimulation Modeling*

PubMed Central

Huang, Yu; Su, Yuzhuo; Rorden, Christopher; Dmochowski, Jacek; Datta, Abhishek; Parra, Lucas C.

2014-01-01

Targeted transcranial stimulation with electric currents requires accurate models of the current flow from scalp electrodes to the human brain. Idiosyncratic anatomy of individual brains and heads leads to significant variability in such current flows across subjects, thus, necessitating accurate individualized head models. Here we report on an automated processing chain that computes current distributions in the head starting from a structural magnetic resonance image (MRI). The main purpose of automating this process is to reduce the substantial effort currently required for manual segmentation, electrode placement, and solving of finite element models. In doing so, several weeks of manual labor were reduced to no more than 4 hours of computation time and minimal user interaction, while current-flow results for the automated method deviated by less than 27.9% from the manual method. Key facilitating factors are the addition of three tissue types (skull, scalp and air) to a state-of-the-art automated segmentation process, morphological processing to correct small but important segmentation errors, and automated placement of small electrodes based on easily reproducible standard electrode configurations. We anticipate that such an automated processing will become an indispensable tool to individualize transcranial direct current stimulation (tDCS) therapy. PMID:23367144

In vivo electrochemical characterization and inflammatory response of multiwalled carbon nanotube-based electrodes in rat hippocampus

NASA Astrophysics Data System (ADS)

Minnikanti, Saugandhika; Pereira, Marilia G. A. G.; Jaraiedi, Sanaz; Jackson, Kassandra; Costa-Neto, Claudio M.; Li, Qiliang; Peixoto, Nathalia

2010-02-01

Stimulating neural electrodes are required to deliver charge to an environment that presents itself as hostile. The electrodes need to maintain their electrical characteristics (charge and impedance) in vivo for a proper functioning of neural prostheses. Here we design implantable multi-walled carbon nanotubes coating for stainless steel substrate electrodes, targeted at wide frequency stimulation of deep brain structures. In well-controlled, low-frequency stimulation acute experiments, we show that multi-walled carbon nanotube electrodes maintain their charge storage capacity (CSC) and impedance in vivo. The difference in average CSCs (n = 4) between the in vivo (1.111 mC cm-2) and in vitro (1.008 mC cm-2) model was statistically insignificant (p > 0.05 or P-value = 0.715, two tailed). We also report on the transcription levels of the pro-inflammatory cytokine IL-1β and TLR2 receptor as an immediate response to low-frequency stimulation using RT-PCR. We show here that the IL-1β is part of the inflammatory response to low-frequency stimulation, but TLR2 is not significantly increased in stimulated tissue when compared to controls. The early stages of neuroinflammation due to mechanical and electrical trauma induced by implants can be better understood by detection of pro-inflammatory molecules rather than by histological studies. Tracking of such quantitative response profits from better analysis methods over several temporal and spatial scales. Our results concerning the evaluation of such inflammatory molecules revealed that transcripts for the cytokine IL-1β are upregulated in response to low-frequency stimulation, whereas no modulation was observed for TLR2. This result indicates that the early response of the brain to mechanical trauma and low-frequency stimulation activates the IL-1β signaling cascade but not that of TLR2.

Visualizing Simulated Electrical Fields from Electroencephalography and Transcranial Electric Brain Stimulation: A Comparative Evaluation

PubMed Central

Eichelbaum, Sebastian; Dannhauer, Moritz; Hlawitschka, Mario; Brooks, Dana; Knösche, Thomas R.; Scheuermann, Gerik

2014-01-01

Electrical activity of neuronal populations is a crucial aspect of brain activity. This activity is not measured directly but recorded as electrical potential changes using head surface electrodes (electroencephalogram - EEG). Head surface electrodes can also be deployed to inject electrical currents in order to modulate brain activity (transcranial electric stimulation techniques) for therapeutic and neuroscientific purposes. In electroencephalography and noninvasive electric brain stimulation, electrical fields mediate between electrical signal sources and regions of interest (ROI). These fields can be very complicated in structure, and are influenced in a complex way by the conductivity profile of the human head. Visualization techniques play a central role to grasp the nature of those fields because such techniques allow for an effective conveyance of complex data and enable quick qualitative and quantitative assessments. The examination of volume conduction effects of particular head model parameterizations (e.g., skull thickness and layering), of brain anomalies (e.g., holes in the skull, tumors), location and extent of active brain areas (e.g., high concentrations of current densities) and around current injecting electrodes can be investigated using visualization. Here, we evaluate a number of widely used visualization techniques, based on either the potential distribution or on the current-flow. In particular, we focus on the extractability of quantitative and qualitative information from the obtained images, their effective integration of anatomical context information, and their interaction. We present illustrative examples from clinically and neuroscientifically relevant cases and discuss the pros and cons of the various visualization techniques. PMID:24821532

Comparison of neural damage induced by electrical stimulation with faradaic and capacitor electrodes.

PubMed

McCreery, D B; Agnew, W F; Yuen, T G; Bullara, L A

1988-01-01

Arrays of platinum (faradaic) and anodized, sintered tantalum pentoxide (capacitor) electrodes were implanted bilaterally in the subdural space of the parietal cortex of the cat. Two weeks after implantation both types of electrodes were pulsed for seven hours with identical waveforms consisting of controlled-current, charge-balanced, symmetric, anodic-first pulse pairs, 400 microseconds/phase and a charge density of 80-100 microC/cm2 (microcoulombs per square cm) at 50 pps (pulses per second). One group of animals was sacrificed immediately following stimulation and a second smaller group one week after stimulation. Tissues beneath both types of pulsed electrodes were damaged, but the difference in damage for the two electrode types was not statistically significant. Tissue beneath unpulsed electrodes was normal. At the ultrastructural level, in animals killed immediately after stimulation, shrunken and hyperchromic neurons were intermixed with neurons showing early intracellular edema. Glial cells appeared essentially normal. In animals killed one week after stimulation most of the damaged neurons had recovered, but the presence of shrunken, vacuolated and degenerating neurons showed that some of the cells were damaged irreversibly. It is concluded that most of the neural damage from stimulations of the brain surface at the level used in this study derives from processes associated with passage of the stimulus current through tissue, such as neuronal hyperactivity rather than electrochemical reactions associated with current injection across the electrode-tissue interface, since such reactions occur only with the faradaic electrodes.

Electric fields in hippocampus due to transcranial focal electrical stimulation via concentric ring electrodes.

PubMed

Besio, Walter G; Hadidi, Ruba; Makeyev, Oleksandr; Luna-Munguía, Hiram; Rocha, Luisa

2011-01-01

As epilepsy affects approximately one percent of the world population, electrical stimulation of brain has recently shown potential as an additive seizure control therapy. In this study we applied focal transcranial electrical stimulation (TFS) on the surface of the skull of rats via concentric ring electrodes. We recorded electric potentials with a bipolar electrode consisting of two stainless steel wires implanted into the left ventral hippocampus. TFS current was gradually increased by 20% starting at 103 μA allowing us to assess the relationship between TFS current and both potentials recorded from the bipolar electrode and the resulting electric field. Generally, increases in TFS current resulted in increases in the electric field. This allows us to estimate what extra-cranial TFS current would be sufficient to cause the activation of neurons in the hippocampus.

Multiple sensor integration for seizure onset detection in human patients comparing conventional disc versus novel tripolar concentric ring electrodes.

PubMed

Makeyev, Oleksandr; Ding, Quan; Martínez-Juárez, Iris E; Gaitanis, John; Kay, Steven M; Besio, Walter G

2013-01-01

As epilepsy affects approximately one percent of the world population, electrical stimulation of the brain has recently shown potential for additive seizure control therapy. Closed-loop systems that apply electrical stimulation when seizure onset is automatically detected require high accuracy of automatic seizure detection based on electrographic brain activity. To improve this accuracy we propose to use noninvasive tripolar concentric ring electrodes that have been shown to have significantly better signal-to-noise ratio, spatial selectivity, and mutual information compared to conventional disc electrodes. The proposed detection methodology is based on integration of multiple sensors using exponentially embedded family (EEF). In this preliminary study it is validated on over 26.3 hours of data collected using both tripolar concentric ring and conventional disc electrodes concurrently each from 7 human patients with epilepsy including five seizures. For a cross-validation based group model EEF correctly detected 100% and 80% of seizures respectively with <0.76 and <1.56 false positive detections per hour respectively for the two electrode modalities. These results clearly suggest the potential of seizure onset detection based on data from tripolar concentric ring electrodes.

Characteristics of electrode impedance and stimulation efficacy of a chronic cortical implant using novel annulus electrodes in rat motor cortex

NASA Astrophysics Data System (ADS)

Wang, Chun; Brunton, Emma; Haghgooie, Saman; Cassells, Kahli; Lowery, Arthur; Rajan, Ramesh

2013-08-01

Objective. Cortical neural prostheses with implanted electrode arrays have been used to restore compromised brain functions but concerns remain regarding their long-term stability and functional performance. Approach. Here we report changes in electrode impedance and stimulation thresholds for a custom-designed electrode array implanted in rat motor cortex for up to three months. Main Results. The array comprises four 2000 µm long electrodes with a large annular stimulating surface (7860-15700 µm2) displaced from the penetrating insulated tip. Compared to pre-implantation in vitro values there were three phases of impedance change: (1) an immediate large increase of impedance by an average of two-fold on implantation; (2) a period of continued impedance increase, albeit with considerable variability, which reached a peak at approximately four weeks post-implantation and remained high over the next two weeks; (3) finally, a period of 5-6 weeks when impedance stabilized at levels close to those seen immediately post-implantation. Impedance could often be temporarily decreased by applying brief trains of current stimulation, used to evoke motor output. The stimulation threshold to induce observable motor behaviour was generally between 75-100 µA, with charge density varying from 48-128 µC cm-2, consistent with the lower current density generated by electrodes with larger stimulating surface area. No systematic change in thresholds occurred over time, suggesting that device functionality was not compromised by the factors that caused changes in electrode impedance. Significance. The present results provide support for the use of annulus electrodes in future applications in cortical neural prostheses.

Deep brain stimulation reveals emotional impact processing in ventromedial prefrontal cortex.

PubMed

Gjedde, Albert; Geday, Jacob

2009-12-07

We tested the hypothesis that modulation of monoaminergic tone with deep-brain stimulation (DBS) of subthalamic nucleus would reveal a site of reactivity in the ventromedial prefrontal cortex that we previously identified by modulating serotonergic and noradrenergic mechanisms by blocking serotonin-noradrenaline reuptake sites. We tested the hypothesis in patients with Parkinson's disease in whom we had measured the changes of blood flow everywhere in the brain associated with the deep brain stimulation of the subthalamic nucleus. We determined the emotional reactivity of the patients as the average impact of emotive images rated by the patients off the DBS. We then searched for sites in the brain that had significant correlation of the changes of blood flow with the emotional impact rated by the patients. The results indicate a significant link between the emotional impact when patients are not stimulated and the change of blood flow associated with the DBS. In subjects with a low emotional impact, activity measured as blood flow rose when the electrode was turned on, while in subjects of high impact, the activity at this site in the ventromedial prefrontal cortex declined when the electrode was turned on. We conclude that changes of neurotransmission in the ventromedial prefrontal cortex had an effect on the tissue that depends on changes of monoamine concentration interacting with specific combinations of inhibitory and excitatory monoamine receptors.

Computational modeling of an endovascular approach to deep brain stimulation

NASA Astrophysics Data System (ADS)

Teplitzky, Benjamin A.; Connolly, Allison T.; Bajwa, Jawad A.; Johnson, Matthew D.

2014-04-01

Objective. Deep brain stimulation (DBS) therapy currently relies on a transcranial neurosurgical technique to implant one or more electrode leads into the brain parenchyma. In this study, we used computational modeling to investigate the feasibility of using an endovascular approach to target DBS therapy. Approach. Image-based anatomical reconstructions of the human brain and vasculature were used to identify 17 established and hypothesized anatomical targets of DBS, of which five were found adjacent to a vein or artery with intraluminal diameter ≥1 mm. Two of these targets, the fornix and subgenual cingulate white matter (SgCwm) tracts, were further investigated using a computational modeling framework that combined segmented volumes of the vascularized brain, finite element models of the tissue voltage during DBS, and multi-compartment axon models to predict the direct electrophysiological effects of endovascular DBS. Main results. The models showed that: (1) a ring-electrode conforming to the vessel wall was more efficient at neural activation than a guidewire design, (2) increasing the length of a ring-electrode had minimal effect on neural activation thresholds, (3) large variability in neural activation occurred with suboptimal placement of a ring-electrode along the targeted vessel, and (4) activation thresholds for the fornix and SgCwm tracts were comparable for endovascular and stereotactic DBS, though endovascular DBS was able to produce significantly larger contralateral activation for a unilateral implantation. Significance. Together, these results suggest that endovascular DBS can serve as a complementary approach to stereotactic DBS in select cases.

Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization.

PubMed

Calabrese, Evan; Hickey, Patrick; Hulette, Christine; Zhang, Jingxian; Parente, Beth; Lad, Shivanand P; Johnson, G Allan

2015-08-01

Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved three-dimensional (3D) reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms. © 2015 Wiley Periodicals, Inc.

Impact of uncertain head tissue conductivity in the optimization of transcranial direct current stimulation for an auditory target

NASA Astrophysics Data System (ADS)

Schmidt, Christian; Wagner, Sven; Burger, Martin; van Rienen, Ursula; Wolters, Carsten H.

2015-08-01

Objective. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique to modify neural excitability. Using multi-array tDCS, we investigate the influence of inter-individually varying head tissue conductivity profiles on optimal electrode configurations for an auditory cortex stimulation. Approach. In order to quantify the uncertainty of the optimal electrode configurations, multi-variate generalized polynomial chaos expansions of the model solutions are used based on uncertain conductivity profiles of the compartments skin, skull, gray matter, and white matter. Stochastic measures, probability density functions, and sensitivity of the quantities of interest are investigated for each electrode and the current density at the target with the resulting stimulation protocols visualized on the head surface. Main results. We demonstrate that the optimized stimulation protocols are only comprised of a few active electrodes, with tolerable deviations in the stimulation amplitude of the anode. However, large deviations in the order of the uncertainty in the conductivity profiles could be noted in the stimulation protocol of the compensating cathodes. Regarding these main stimulation electrodes, the stimulation protocol was most sensitive to uncertainty in skull conductivity. Finally, the probability that the current density amplitude in the auditory cortex target region is supra-threshold was below 50%. Significance. The results suggest that an uncertain conductivity profile in computational models of tDCS can have a substantial influence on the prediction of optimal stimulation protocols for stimulation of the auditory cortex. The investigations carried out in this study present a possibility to predict the probability of providing a therapeutic effect with an optimized electrode system for future auditory clinical and experimental procedures of tDCS applications.

Carbon Nanofiber Nanoelectrodes for Biosensing Applications

NASA Technical Reports Server (NTRS)

Koehne, Jessica Erin

2014-01-01

A sensor platform based on vertically aligned carbon nanofibers (CNFs) has been developed. Their inherent nanometer scale, high conductivity, wide potential window, good biocompatibility and well-defined surface chemistry make them ideal candidates as biosensor electrodes. Here, we report two studies using vertically aligned CNF nanoelectrodes for biomedical applications. CNF arrays are investigated as neural stimulation and neurotransmitter recording electrodes for application in deep brain stimulation (DBS). Polypyrrole coated CNF nanoelectrodes have shown great promise as stimulating electrodes due to their large surface area, low impedance, biocompatibility and capacity for highly localized stimulation. CNFs embedded in SiO2 have been used as sensing electrodes for neurotransmitter detection. Our approach combines a multiplexed CNF electrode chip, developed at NASA Ames Research Center, with the Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS) system, developed at the Mayo Clinic. Preliminary results indicate that the CNF nanoelectrode arrays are easily integrated with WINCS for neurotransmitter detection in a multiplexed array format. In the future, combining CNF based stimulating and recording electrodes with WINCS may lay the foundation for an implantable smart therapeutic system that utilizes neurochemical feedback control while likely resulting in increased DBS application in various neuropsychiatric disorders. In total, our goal is to take advantage of the nanostructure of CNF arrays for biosensing studies requiring ultrahigh sensitivity, high-degree of miniaturization, and selective biofunctionalization.

Deep Brain Stimulation for Essential Tremor: Aligning Thalamic and Posterior Subthalamic Targets in 1 Surgical Trajectory.

PubMed

Bot, Maarten; van Rootselaar, Fleur; Contarino, Maria Fiorella; Odekerken, Vincent; Dijk, Joke; de Bie, Rob; Schuurman, Richard; van den Munckhof, Pepijn

2017-12-21

Ventral intermediate nucleus (VIM) deep brain stimulation (DBS) and posterior subthalamic area (PSA) DBS suppress tremor in essential tremor (ET) patients, but it is not clear which target is optimal. Aligning both targets in 1 surgical trajectory would facilitate exploring stimulation of either target in a single patient. To evaluate aligning VIM and PSA in 1 surgical trajectory for DBS in ET. Technical aspects of trajectories, intraoperative stimulation findings, final electrode placement, target used for chronic stimulation, and adverse and beneficial effects were evaluated. In 17 patients representing 33 trajectories, we successfully aligned VIM and PSA targets in 26 trajectories. Trajectory distance between targets averaged 7.2 (range 6-10) mm. In all but 4 aligned trajectories, optimal intraoperative tremor suppression was obtained in the PSA. During follow-up, active electrode contacts were located in PSA in the majority of cases. Overall, successful tremor control was achieved in 69% of patients. Stimulation-induced dysarthria or gait ataxia occurred in, respectively, 56% and 44% of patients. Neither difference in tremor suppression or side effects was noted between aligned and nonaligned leads nor between the different locations of chronic stimulation. Alignment of VIM and PSA for DBS in ET is feasible and enables intraoperative exploration of both targets in 1 trajectory. This facilitates positioning of electrode contacts in both areas, where multiple effective points of stimulation can be found. In the majority of aligned leads, optimal intraoperative and chronic stimulation were located in the PSA. Copyright © 2017 by the Congress of Neurological Surgeons

Focal Hemodynamic Responses in the Stimulated Hemisphere During High-Definition Transcranial Direct Current Stimulation.

PubMed

Muthalib, Makii; Besson, Pierre; Rothwell, John; Perrey, Stéphane

2017-07-17

High-definition transcranial direct current stimulation (HD-tDCS) using a 4 × 1 electrode montage has been previously shown using modeling and physiological studies to constrain the electric field within the spatial extent of the electrodes. The aim of this proof-of-concept study was to determine if functional near-infrared spectroscopy (fNIRS) neuroimaging can be used to determine a hemodynamic correlate of this 4 × 1 HD-tDCS electric field on the brain. In a three session cross-over study design, 13 healthy males received one sham (2 mA, 30 sec) and two real (HD-tDCS-1 and HD-tDCS-2, 2 mA, 10 min) anodal HD-tDCS targeting the left M1 via a 4 × 1 electrode montage (anode on C3 and 4 return electrodes 3.5 cm from anode). The two real HD-tDCS sessions afforded a within-subject replication of the findings. fNIRS was used to measure changes in brain hemodynamics (oxygenated hemoglobin integral-O 2 Hb int ) during each 10 min session from two regions of interest (ROIs) in the stimulated left hemisphere that corresponded to "within" (L in ) and "outside" (L out ) the spatial extent of the 4 × 1 electrode montage, and two corresponding ROIs (R in and R out ) in the right hemisphere. The ANOVA showed that both real anodal HD-tDCS compared to sham induced a significantly greater O 2 Hb int in the L in than L out ROIs of the stimulated left hemisphere; while there were no significant differences between the real and sham sessions for the right hemisphere ROIs. Intra-class correlation coefficients showed "fair-to-good" reproducibility for the left stimulated hemisphere ROIs. The greater O 2 Hb int "within" than "outside" the spatial extent of the 4 × 1 electrode montage represents a hemodynamic correlate of the electrical field distribution, and thus provides a prospective reliable method to determine the dose of stimulation that is necessary to optimize HD-tDCS parameters in various applications. © 2017 International Neuromodulation Society.

Visual-spatial memory may be enhanced with theta burst deep brain stimulation of the fornix: a preliminary investigation with four cases.

PubMed

Miller, Jonathan P; Sweet, Jennifer A; Bailey, Christopher M; Munyon, Charles N; Luders, Hans O; Fastenau, Philip S

2015-07-01

Memory loss after brain injury can be a source of considerable morbidity, but there are presently few therapeutic options for restoring memory function. We have previously demonstrated that burst stimulation of the fornix is able to significantly improve memory in a rodent model of traumatic brain injury. The present study is a preliminary investigation with a small group of cases to explore whether theta burst stimulation of the fornix might improve memory in humans. Four individuals undergoing stereo-electroencephalography evaluation for drug-resistant epilepsy were enrolled. All participants were implanted with an electrode into the proximal fornix and dorsal hippocampal commissure on the language dominant (n = 3) or language non-dominant (n = 1) side, and stimulation of this electrode reliably produced a diffuse evoked potential in the head and body of the ipsilateral hippocampus. Each participant underwent testing of verbal memory (Rey Auditory-Verbal Learning Test), visual-spatial memory (Medical College of Georgia Complex Figure Test), and visual confrontational naming (Boston Naming Test Short Form) once per day over at least two consecutive days using novel test forms each day. For 50% of the trials, the fornix electrode was continuously stimulated using a burst pattern (200 Hz in 100 ms trains, five trains per second, 100 µs, 7 mA) and was compared with sham stimulation. Participants and examiners were blinded to whether stimulation was active or not, and the order of stimulation was randomized. The small sample size precluded use of inferential statistics; therefore, data were analysed using descriptive statistics and graphic analysis. Burst stimulation of the fornix was not perceived by any of the participants but was associated with a robust reversible improvement in immediate and delayed performance on the Medical College of Georgia Complex Figure Test. There were no apparent differences on either Rey Auditory-Verbal Learning Test or Boston Naming Test. There was no apparent relationship between performance and side of stimulation (language dominant or non-dominant). There were no complications. Preliminary evidence in this small sample of patients with drug-resistant epilepsy suggests that theta burst stimulation of the fornix may be associated with improvement in visual-spatial memory. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Influence of the implanted pulse generator as reference electrode in finite element model of monopolar deep brain stimulation.

PubMed

Walckiers, Grégoire; Fuchs, Benjamin; Thiran, Jean-Philippe; Mosig, Juan R; Pollo, Claudio

2010-01-30

Electrical deep brain stimulation (DBS) is an efficient method to treat movement disorders. Many models of DBS, based mostly on finite elements, have recently been proposed to better understand the interaction between the electrical stimulation and the brain tissues. In monopolar DBS, clinically widely used, the implanted pulse generator (IPG) is used as reference electrode (RE). In this paper, the influence of the RE model of monopolar DBS is investigated. For that purpose, a finite element model of the full electric loop including the head, the neck and the superior chest is used. Head, neck and superior chest are made of simple structures such as parallelepipeds and cylinders. The tissues surrounding the electrode are accurately modelled from data provided by the diffusion tensor magnetic resonance imaging (DT-MRI). Three different configurations of RE are compared with a commonly used model of reduced size. The electrical impedance seen by the DBS system and the potential distribution are computed for each model. Moreover, axons are modelled to compute the area of tissue activated by stimulation. Results show that these indicators are influenced by the surface and position of the RE. The use of a RE model corresponding to the implanted device rather than the usually simplified model leads to an increase of the system impedance (+48%) and a reduction of the area of activated tissue (-15%). (c) 2009 Elsevier B.V. All rights reserved.

EDITORIAL: Focus on the neural interface Focus on the neural interface

NASA Astrophysics Data System (ADS)

Durand, Dominique M.

2009-10-01

The possibility of an effective connection between neural tissue and computers has inspired scientists and engineers to develop new ways of controlling and obtaining information from the nervous system. These applications range from `brain hacking' to neural control of artificial limbs with brain signals. Notwithstanding the significant advances in neural prosthetics in the last few decades and the success of some stimulation devices such as cochlear prosthesis, neurotechnology remains below its potential for restoring neural function in patients with nervous system disorders. One of the reasons for this limited impact can be found at the neural interface and close attention to the integration between electrodes and tissue should improve the possibility of successful outcomes. The neural interfaces research community consists of investigators working in areas such as deep brain stimulation, functional neuromuscular/electrical stimulation, auditory prostheses, cortical prostheses, neuromodulation, microelectrode array technology, brain-computer/machine interfaces. Following the success of previous neuroprostheses and neural interfaces workshops, funding (from NIH) was obtained to establish a biennial conference in the area of neural interfaces. The first Neural Interfaces Conference took place in Cleveland, OH in 2008 and several topics from this conference have been selected for publication in this special section of the Journal of Neural Engineering. Three `perspectives' review the areas of neural regeneration (Corredor and Goldberg), cochlear implants (O'Leary et al) and neural prostheses (Anderson). Seven articles focus on various aspects of neural interfacing. One of the most popular of these areas is the field of brain-computer interfaces. Fraser et al, report on a method to generate robust control with simple signal processing algorithms of signals obtained with electrodes implanted in the brain. One problem with implanted electrode arrays, however, is that they can fail to record reliably neural signals for long periods of time. McConnell et al show that by measuring the impedance of the tissue, one can evaluate the extent of the tissue response to the presence of the electrode. Another problem with the neural interface is the mismatch of the mechanical properties between electrode and tissue. Basinger et al use finite element modeling to analyze this mismatch in retinal prostheses and guide the design of new implantable devices. Electrical stimulation has been the method of choice to activate externally the nervous system. However, Zhang et al show that a novel dual hybrid device integrating electrical and optical stimulation can provide an effective interface for simultaneous recording and stimulation. By interfacing an EMG recording system and a movement detection system, Johnson and Fuglevand develop a model capable of predicting muscle activity during movement that could be important for the development of motor prostheses. Sensory restoration is another unsolved problem in neural prostheses. By developing a novel interface between the dorsal root ganglia and electrodes arrays, Gaunt et al show that it is possible to recruit afferent fibers for sensory substitution. Finally, by interfacing directly with muscles, Jung and colleagues show that stimulation of muscles involved in locomotion following spinal cord damage in rats can provide an effective treatment modality for incomplete spinal cord injury. This series of articles clearly shows that the interface is indeed one of the keys to successful therapeutic neural devices. The next Neural Interfaces Conference will take place in Los Angeles, CA in June 2010 and one can expect to see new developments in neural engineering obtained by focusing on the neural interface.

Fundamentals of Transcranial Electric and Magnetic Stimulation Dose: Definition, Selection, and Reporting Practices

PubMed Central

Peterchev, Angel V.; Wagner, Timothy A.; Miranda, Pedro C.; Nitsche, Michael A.; Paulus, Walter; Lisanby, Sarah H.; Pascual-Leone, Alvaro; Bikson, Marom

2011-01-01

The growing use of transcranial electric and magnetic (EM) brain stimulation in basic research and in clinical applications necessitates a clear understanding of what constitutes the dose of EM stimulation and how it should be reported. The biological effects of EM stimulation are mediated through an electromagnetic field injected (via electric stimulation) or induced (via magnetic stimulation) in the body. Therefore, transcranial EM stimulation dose ought to be defined by all parameters of the stimulation device that affect the electromagnetic field generated in the body, including the stimulation electrode or coil configuration parameters: shape, size, position, and electrical properties, as well as the electrode or coil current (or voltage) waveform parameters: pulse shape, amplitude, width, polarity, and repetition frequency; duration of and interval between bursts or trains of pulses; total number of pulses; and interval between stimulation sessions and total number of sessions. Knowledge of the electromagnetic field generated in the body may not be sufficient but is necessary to understand the biological effects of EM stimulation. We believe that reporting of EM stimulation dose should be guided by the principle of reproducibility: sufficient information about the stimulation parameters should be provided so that the dose can be replicated. This paper provides fundamental definition and principles for reporting of dose that encompass any transcranial EM brain stimulation protocol. PMID:22305345

Fundamentals of transcranial electric and magnetic stimulation dose: definition, selection, and reporting practices.

PubMed

Peterchev, Angel V; Wagner, Timothy A; Miranda, Pedro C; Nitsche, Michael A; Paulus, Walter; Lisanby, Sarah H; Pascual-Leone, Alvaro; Bikson, Marom

2012-10-01

The growing use of transcranial electric and magnetic (EM) brain stimulation in basic research and in clinical applications necessitates a clear understanding of what constitutes the dose of EM stimulation and how it should be reported. This paper provides fundamental definitions and principles for reporting of dose that encompass any transcranial EM brain stimulation protocol. The biologic effects of EM stimulation are mediated through an electromagnetic field injected (via electric stimulation) or induced (via magnetic stimulation) in the body. Therefore, transcranial EM stimulation dose ought to be defined by all parameters of the stimulation device that affect the electromagnetic field generated in the body, including the stimulation electrode or coil configuration parameters: shape, size, position, and electrical properties, as well as the electrode or coil current (or voltage) waveform parameters: pulse shape, amplitude, width, polarity, and repetition frequency; duration of and interval between bursts or trains of pulses; total number of pulses; and interval between stimulation sessions and total number of sessions. Knowledge of the electromagnetic field generated in the body may not be sufficient but is necessary to understand the biologic effects of EM stimulation. We believe that reporting of EM stimulation dose should be guided by the principle of reproducibility: sufficient information about the stimulation parameters should be provided so that the dose can be replicated. Copyright © 2012 Elsevier Inc. All rights reserved.

Validation of a Portable Low-Power Deep Brain Stimulation Device Through Anxiolytic Effects in a Laboratory Rat Model.

PubMed

Kouzani, Abbas Z; Kale, Rajas P; Zarate-Garza, Pablo Patricio; Berk, Michael; Walder, Ken; Tye, Susannah J

2017-09-01

Deep brain stimulation (DBS) devices deliver electrical pulses to neural tissue through an electrode. To study the mechanisms and therapeutic benefits of deep brain stimulation, murine preclinical research is necessary. However, conducting naturalistic long-term, uninterrupted animal behavioral experiments can be difficult with bench-top systems. The reduction of size, weight, power consumption, and cost of DBS devices can assist the progress of this research in animal studies. A low power, low weight, miniature DBS device is presented in this paper. This device consists of electronic hardware and software components including a low-power microcontroller, an adjustable current source, an n-channel metal-oxide-semiconductor field-effect transistor, a coin-cell battery, electrode wires and a software program to operate the device. Evaluation of the performance of the device in terms of battery lifetime and device functionality through bench and in vivo tests was conducted. The bench test revealed that this device can deliver continuous stimulation current pulses of strength [Formula: see text], width [Formula: see text], and frequency 130 Hz for over 22 days. The in vivo tests demonstrated that chronic stimulation of the nucleus accumbens (NAc) with this device significantly increased psychomotor activity, together with a dramatic reduction in anxiety-like behavior in the elevated zero-maze test.

Technical nuances to minimize common complications of deep brain stimulation.

PubMed

House, Paul

2017-04-01

The implantation of deep brain stimulator electrodes is associated with infrequent complications. These complications are consistent across prospective trials and include infection, skin erosion, hemorrhage, and lead misplacement. Nuances of surgical technique can be used to minimize the risk of these commonly noted complications. Several of these technical nuances are highlighted in this video submission. The video can be found here: https://youtu.be/GL09W9p013g .

Particle Swarm Optimization for Programming Deep Brain Stimulation Arrays

PubMed Central

Peña, Edgar; Zhang, Simeng; Deyo, Steve; Xiao, YiZi; Johnson, Matthew D.

2017-01-01

Objective Deep brain stimulation (DBS) therapy relies on both precise neurosurgical targeting and systematic optimization of stimulation settings to achieve beneficial clinical outcomes. One recent advance to improve targeting is the development of DBS arrays (DBSAs) with electrodes segmented both along and around the DBS lead. However, increasing the number of independent electrodes creates the logistical challenge of optimizing stimulation parameters efficiently. Approach Solving such complex problems with multiple solutions and objectives is well known to occur in biology, in which complex collective behaviors emerge out of swarms of individual organisms engaged in learning through social interactions. Here, we developed a particle swarm optimization (PSO) algorithm to program DBSAs using a swarm of individual particles representing electrode configurations and stimulation amplitudes. Using a finite element model of motor thalamic DBS, we demonstrate how the PSO algorithm can efficiently optimize a multi-objective function that maximizes predictions of axonal activation in regions of interest (ROI, cerebellar-receiving area of motor thalamus), minimizes predictions of axonal activation in regions of avoidance (ROA, somatosensory thalamus), and minimizes power consumption. Main Results The algorithm solved the multi-objective problem by producing a Pareto front. ROI and ROA activation predictions were consistent across swarms (<1% median discrepancy in axon activation). The algorithm was able to accommodate for (1) lead displacement (1 mm) with relatively small ROI (≤9.2%) and ROA (≤1%) activation changes, irrespective of shift direction; (2) reduction in maximum per-electrode current (by 50% and 80%) with ROI activation decreasing by 5.6% and 16%, respectively; and (3) disabling electrodes (n=3 and 12) with ROI activation reduction by 1.8% and 14%, respectively. Additionally, comparison between PSO predictions and multi-compartment axon model simulations showed discrepancies of <1% between approaches. Significance The PSO algorithm provides a computationally efficient way to program DBS systems especially those with higher electrode counts. PMID:28068291

Particle swarm optimization for programming deep brain stimulation arrays

NASA Astrophysics Data System (ADS)

Peña, Edgar; Zhang, Simeng; Deyo, Steve; Xiao, YiZi; Johnson, Matthew D.

2017-02-01

Objective. Deep brain stimulation (DBS) therapy relies on both precise neurosurgical targeting and systematic optimization of stimulation settings to achieve beneficial clinical outcomes. One recent advance to improve targeting is the development of DBS arrays (DBSAs) with electrodes segmented both along and around the DBS lead. However, increasing the number of independent electrodes creates the logistical challenge of optimizing stimulation parameters efficiently. Approach. Solving such complex problems with multiple solutions and objectives is well known to occur in biology, in which complex collective behaviors emerge out of swarms of individual organisms engaged in learning through social interactions. Here, we developed a particle swarm optimization (PSO) algorithm to program DBSAs using a swarm of individual particles representing electrode configurations and stimulation amplitudes. Using a finite element model of motor thalamic DBS, we demonstrate how the PSO algorithm can efficiently optimize a multi-objective function that maximizes predictions of axonal activation in regions of interest (ROI, cerebellar-receiving area of motor thalamus), minimizes predictions of axonal activation in regions of avoidance (ROA, somatosensory thalamus), and minimizes power consumption. Main results. The algorithm solved the multi-objective problem by producing a Pareto front. ROI and ROA activation predictions were consistent across swarms (<1% median discrepancy in axon activation). The algorithm was able to accommodate for (1) lead displacement (1 mm) with relatively small ROI (⩽9.2%) and ROA (⩽1%) activation changes, irrespective of shift direction; (2) reduction in maximum per-electrode current (by 50% and 80%) with ROI activation decreasing by 5.6% and 16%, respectively; and (3) disabling electrodes (n  =  3 and 12) with ROI activation reduction by 1.8% and 14%, respectively. Additionally, comparison between PSO predictions and multi-compartment axon model simulations showed discrepancies of  <1% between approaches. Significance. The PSO algorithm provides a computationally efficient way to program DBS systems especially those with higher electrode counts.

Control of a brain-computer interface using stereotactic depth electrodes in and adjacent to the hippocampus

NASA Astrophysics Data System (ADS)

Krusienski, D. J.; Shih, J. J.

2011-04-01

A brain-computer interface (BCI) is a device that enables severely disabled people to communicate and interact with their environments using their brain waves. Most research investigating BCI in humans has used scalp-recorded electroencephalography or intracranial electrocorticography. The use of brain signals obtained directly from stereotactic depth electrodes to control a BCI has not previously been explored. In this study, event-related potentials (ERPs) recorded from bilateral stereotactic depth electrodes implanted in and adjacent to the hippocampus were used to control a P300 Speller paradigm. The ERPs were preprocessed and used to train a linear classifier to subsequently predict the intended target letters. The classifier was able to predict the intended target character at or near 100% accuracy using fewer than 15 stimulation sequences in the two subjects tested. Our results demonstrate that ERPs from hippocampal and hippocampal adjacent depth electrodes can be used to reliably control the P300 Speller BCI paradigm.

Motor outcome and electrode location in deep brain stimulation in Parkinson's disease.

PubMed

Koivu, Maija; Huotarinen, Antti; Scheperjans, Filip; Laakso, Aki; Kivisaari, Riku; Pekkonen, Eero

2018-05-30

To evaluate the efficacy and adverse effects of subthalamic deep brain stimulation (STN-DBS) in patients with advanced Parkinson's disease (PD) and the possible correlation between electrode location and clinical outcome. We retrospectively reviewed 87 PD-related STN-DBS operations at Helsinki University Hospital (HUH) from 2007 to 2014. The changes of Unified Parkinson's Disease Rating Scale (UPDRS) part III score, Hoehn & Yahr stage, antiparkinson medication, and adverse effects were studied. We estimated the active electrode location in three different coordinate systems: direct visual analysis of MRI correlated to brain atlas, location in relation to the nucleus borders and location in relation to the midcommisural point. At 6 months after operation, both levodopa equivalent doses (LEDs; 35%, Wilcoxon signed-rank test = 0.000) and UPDRS part III scores significantly decreased (38%, Wilcoxon signed-rank test = 0.000). Four patients (5%) suffered from moderate DBS-related dysarthria. The generator and electrodes had to be removed in one patient due to infection (1%). Electrode coordinates in the three coordinate systems correlated well with each other. On the left side, more ventral location of the active contact was associated with greater LED decrease. STN-DBS improves motor function and enables the reduction in antiparkinson medication with an acceptable adverse effect profile. More ventral location of the active contact may allow stronger LED reduction. Further research on the correlation between contact location, clinical outcome, and LED reduction is warranted. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

Effect of brain shift on the creation of functional atlases for deep brain stimulation surgery

PubMed Central

Pallavaram, Srivatsan; Remple, Michael S.; Neimat, Joseph S.; Kao, Chris; Konrad, Peter E.; D’Haese, Pierre-François

2011-01-01

Purpose In the recent past many groups have tried to build functional atlases of the deep brain using intra-operatively acquired information such as stimulation responses or micro-electrode recordings. An underlying assumption in building such atlases is that anatomical structures do not move between pre-operative imaging and intra-operative recording. In this study, we present evidences that this assumption is not valid. We quantify the effect of brain shift between pre-operative imaging and intra-operative recording on the creation of functional atlases using intra-operative somatotopy recordings and stimulation response data. Methods A total of 73 somatotopy points from 24 bilateral subthalamic nucleus (STN) implantations and 52 eye deviation stimulation response points from 17 bilateral STN implantations were used. These points were spatially normalized on a magnetic resonance imaging (MRI) atlas using a fully automatic non-rigid registration algorithm. Each implantation was categorized as having low, medium or large brain shift based on the amount of pneumocephalus visible on post-operative CT. The locations of somatotopy clusters and stimulation maps were analyzed for each category. Results The centroid of the large brain shift cluster of the somatotopy data (posterior, lateral, inferior: 3.06, 11.27, 5.36 mm) was found posterior, medial and inferior to that of the medium cluster (2.90, 13.57, 4.53 mm) which was posterior, medial and inferior to that of the low shift cluster (1.94, 13.92, 3.20 mm). The coordinates are referenced with respect to the mid-commissural point. Euclidean distances between the centroids were 1.68, 2.44 and 3.59 mm, respectively for low-medium, medium-large and low-large shift clusters. We found similar trends for the positions of the stimulation maps. The Euclidian distance between the highest probability locations on the low and medium-large shift maps was 4.06 mm. Conclusion The effect of brain shift in deep brain stimulation (DBS) surgery has been demonstrated using intra-operative somatotopy recordings as well as stimulation response data. The results not only indicate that considerable brain shift happens before micro-electrode recordings in DBS but also that brain shift affects the creation of accurate functional atlases. Therefore, care must be taken when building and using such atlases of intra-operative data and also when using intra-operative data to validate anatomical atlases. PMID:20033503

Minimum Electric Field Exposure for Seizure Induction with Electroconvulsive Therapy and Magnetic Seizure Therapy.

PubMed

Lee, Won H; Lisanby, Sarah H; Laine, Andrew F; Peterchev, Angel V

2017-05-01

Lowering and individualizing the current amplitude in electroconvulsive therapy (ECT) has been proposed as a means to produce stimulation closer to the neural activation threshold and more focal seizure induction, which could potentially reduce cognitive side effects. However, the effect of current amplitude on the electric field (E-field) in the brain has not been previously linked to the current amplitude threshold for seizure induction. We coupled MRI-based E-field models with amplitude titrations of motor threshold (MT) and seizure threshold (ST) in four nonhuman primates (NHPs) to determine the strength, distribution, and focality of stimulation in the brain for four ECT electrode configurations (bilateral, bifrontal, right-unilateral, and frontomedial) and magnetic seizure therapy (MST) with cap coil on vertex. At the amplitude-titrated ST, the stimulated brain subvolume (23-63%) was significantly less than for conventional ECT with high, fixed current (94-99%). The focality of amplitude-titrated right-unilateral ECT (25%) was comparable to cap coil MST (23%), demonstrating that ECT with a low current amplitude and focal electrode placement can induce seizures with E-field as focal as MST, although these electrode and coil configurations affect differently specific brain regions. Individualizing the current amplitude reduced interindividual variation in the stimulation focality by 40-53% for ECT and 26% for MST, supporting amplitude individualization as a means of dosing especially for ECT. There was an overall significant correlation between the measured amplitude-titrated ST and the prediction of the E-field models, supporting a potential role of these models in dosing of ECT and MST. These findings may guide the development of seizure therapy dosing paradigms with improved risk/benefit ratio.

iELVis: An open source MATLAB toolbox for localizing and visualizing human intracranial electrode data.

PubMed

Groppe, David M; Bickel, Stephan; Dykstra, Andrew R; Wang, Xiuyuan; Mégevand, Pierre; Mercier, Manuel R; Lado, Fred A; Mehta, Ashesh D; Honey, Christopher J

2017-04-01

Intracranial electrical recordings (iEEG) and brain stimulation (iEBS) are invaluable human neuroscience methodologies. However, the value of such data is often unrealized as many laboratories lack tools for localizing electrodes relative to anatomy. To remedy this, we have developed a MATLAB toolbox for intracranial electrode localization and visualization, iELVis. NEW METHOD: iELVis uses existing tools (BioImage Suite, FSL, and FreeSurfer) for preimplant magnetic resonance imaging (MRI) segmentation, neuroimaging coregistration, and manual identification of electrodes in postimplant neuroimaging. Subsequently, iELVis implements methods for correcting electrode locations for postimplant brain shift with millimeter-scale accuracy and provides interactive visualization on 3D surfaces or in 2D slices with optional functional neuroimaging overlays. iELVis also localizes electrodes relative to FreeSurfer-based atlases and can combine data across subjects via the FreeSurfer average brain. It takes 30-60min of user time and 12-24h of computer time to localize and visualize electrodes from one brain. We demonstrate iELVis's functionality by showing that three methods for mapping primary hand somatosensory cortex (iEEG, iEBS, and functional MRI) provide highly concordant results. COMPARISON WITH EXISTING METHODS: iELVis is the first public software for electrode localization that corrects for brain shift, maps electrodes to an average brain, and supports neuroimaging overlays. Moreover, its interactive visualizations are powerful and its tutorial material is extensive. iELVis promises to speed the progress and enhance the robustness of intracranial electrode research. The software and extensive tutorial materials are freely available as part of the EpiSurg software project: https://github.com/episurg/episurg. Copyright © 2017 Elsevier B.V. All rights reserved.

Determinants of the electric field during transcranial direct current stimulation.

PubMed

Opitz, Alexander; Paulus, Walter; Will, Susanne; Antunes, Andre; Thielscher, Axel

2015-04-01

Transcranial direct current stimulation (tDCS) causes a complex spatial distribution of the electric current flow in the head which hampers the accurate localization of the stimulated brain areas. In this study we show how various anatomical features systematically shape the electric field distribution in the brain during tDCS. We constructed anatomically realistic finite element (FEM) models of two individual heads including conductivity anisotropy and different skull layers. We simulated a widely employed electrode montage to induce motor cortex plasticity and moved the stimulating electrode over the motor cortex in small steps to examine the resulting changes of the electric field distribution in the underlying cortex. We examined the effect of skull thickness and composition on the passing currents showing that thinner skull regions lead to higher electric field strengths. This effect is counteracted by a larger proportion of higher conducting spongy bone in thicker regions leading to a more homogenous current over the skull. Using a multiple regression model we could identify key factors that determine the field distribution to a significant extent, namely the thicknesses of the cerebrospinal fluid and the skull, the gyral depth and the distance to the anode and cathode. These factors account for up to 50% of the spatial variation of the electric field strength. Further, we demonstrate that individual anatomical factors can lead to stimulation "hotspots" which are partly resistant to electrode positioning. Our results give valuable novel insights in the biophysical foundation of tDCS and highlight the importance to account for individual anatomical factors when choosing an electrode montage. Copyright © 2015 Elsevier Inc. All rights reserved.

Electrodes for high-definition transcutaneous DC stimulation for applications in drug delivery and electrotherapy, including tDCS.

PubMed

Minhas, Preet; Bansal, Varun; Patel, Jinal; Ho, Johnson S; Diaz, Julian; Datta, Abhishek; Bikson, Marom

2010-07-15

Transcutaneous electrical stimulation is applied in a range of biomedical applications including transcranial direct current stimulation (tDCS). tDCS is a non-invasive procedure where a weak direct current (<2 mA) is applied across the scalp to modulate brain function. High-definition tDCS (HD-tDCS) is a technique used to increase the spatial focality of tDCS by passing current across the scalp using <12 mm diameter electrodes. The purpose of this study was to design and optimize "high-definition" electrode-gel parameters for electrode durability, skin safety and subjective pain. Anode and cathode electrode potential, temperature, pH and subjective sensation over time were assessed during application of 2 mA direct current, for up to 22 min on agar gel or subject forearms. A selection of five types of solid-conductors (Ag pellet, Ag/AgCl pellet, rubber pellet, Ag/AgCl ring and Ag/AgCl disc) and seven conductive gels (Signa, Spectra, Tensive, Redux, BioGel, Lectron and CCNY-4) were investigated. The Ag/AgCl ring in combination with CCNY-4 gel resulted in the most favorable outcomes. Under anode stimulations, electrode potential and temperature rises were generally observed in all electrode-gel combinations except for Ag/AgCl ring and disc electrodes. pH remained constant for all solid-conductors except for both Ag and rubber pellet electrodes with Signa and CCNY-4 gels. Sensation ratings were independent of stimulation polarity. Ag/AgCl ring electrodes were found to be the most comfortable followed by Ag, rubber and Ag/AgCl pellet electrodes across all gels. Copyright 2010 Elsevier B.V. All rights reserved.

Electrodes for high-definition transcutaneous DC stimulation for applications in drug-delivery and electrotherapy, including tDCS

PubMed Central

Minhas, Preet; Bansal, Varun; Patel, Jinal; Ho, Johnson S.; Diaz, Julian; Datta, Abhishek; Bikson, Marom

2010-01-01

Transcutaneous electrical stimulation is applied in a range of biomedical applications including Transcranial Direct Current Stimulation (tDCS). tDCS is a non-invasive procedure where a weak direct current (<2 mA) is applied across the scalp to modulate brain function. High-Definition tDCS (HD-tDCS) is a technique used to increase the spatial focality of tDCS by passing current across the scalp using <12 mm diameter electrodes. The purpose of this study was to design and optimize “high-definition” electrode-gel parameters for electrode durability, skin safety, and subjective pain. Anode and cathode electrode potential, temperature, pH, and subjective sensation over time were assessed during application of 2 mA direct current, for up to 22 minutes on agar gel or subject forearms. A selection of 5 types of solid-conductors (Ag pellet, Ag/AgCl pellet, Rubber pellet, Ag/AgCl ring, and Ag/AgCl disc) and 7 conductive gels (Signa, Spectra, Tensive, Redux, BioGel, Lectron, and CCNY-4) were investigated. The Ag/AgCl ring in combination with CCNY-4 gel resulted in the most favorable outcomes. Under anode stimulations, electrode potential and temperature rises were generally observed in all electrode-gel combinations except for Ag/AgCl ring and disc electrodes. pH remained constant for all solid-conductors except for both Ag and Rubber pellet electrodes with Signa and CCNY-4 gels. Sensation ratings were independent of stimulation polarity. Ag/AgCl ring electrodes were found to be the most comfortable followed by Ag, Rubber, and Ag/AgCl pellet electrodes across all gels. PMID:20488204

Cranial electrotherapy stimulation and transcranial pulsed current stimulation: a computer based high-resolution modeling study.

PubMed

Datta, Abhishek; Dmochowski, Jacek P; Guleyupoglu, Berkan; Bikson, Marom; Fregni, Felipe

2013-01-15

The field of non-invasive brain stimulation has developed significantly over the last two decades. Though two techniques of noninvasive brain stimulation--transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS)--are becoming established tools for research in neuroscience and for some clinical applications, related techniques that also show some promising clinical results have not been developed at the same pace. One of these related techniques is cranial electrotherapy stimulation (CES), a class of transcranial pulsed current stimulation (tPCS). In order to understand further the mechanisms of CES, we aimed to model CES using a magnetic resonance imaging (MRI)-derived finite element head model including cortical and also subcortical structures. Cortical electric field (current density) peak intensities and distributions were analyzed. We evaluated different electrode configurations of CES including in-ear and over-ear montages. Our results confirm that significant amounts of current pass the skull and reach cortical and subcortical structures. In addition, depending on the montage, induced currents at subcortical areas, such as midbrain, pons, thalamus and hypothalamus are of similar magnitude than that of cortical areas. Incremental variations of electrode position on the head surface also influence which cortical regions are modulated. The high-resolution modeling predictions suggest that details of electrode montage influence current flow through superficial and deep structures. Finally we present laptop based methods for tPCS dose design using dominant frequency and spherical models. These modeling predictions and tools are the first step to advance rational and optimized use of tPCS and CES. Copyright © 2012 Elsevier Inc. All rights reserved.

MEG Can Map Short and Long-Term Changes in Brain Activity following Deep Brain Stimulation for Chronic Pain

PubMed Central

Mohseni, Hamid R.; Smith, Penny P.; Parsons, Christine E.; Young, Katherine S.; Hyam, Jonathan A.; Stein, Alan; Stein, John F.; Green, Alexander L.; Aziz, Tipu Z.; Kringelbach, Morten L.

2012-01-01

Deep brain stimulation (DBS) has been shown to be clinically effective for some forms of treatment-resistant chronic pain, but the precise mechanisms of action are not well understood. Here, we present an analysis of magnetoencephalography (MEG) data from a patient with whole-body chronic pain, in order to investigate changes in neural activity induced by DBS for pain relief over both short- and long-term. This patient is one of the few cases treated using DBS of the anterior cingulate cortex (ACC). We demonstrate that a novel method, null-beamforming, can be used to localise accurately brain activity despite the artefacts caused by the presence of DBS electrodes and stimulus pulses. The accuracy of our source localisation was verified by correlating the predicted DBS electrode positions with their actual positions. Using this beamforming method, we examined changes in whole-brain activity comparing pain relief achieved with deep brain stimulation (DBS ON) and compared with pain experienced with no stimulation (DBS OFF). We found significant changes in activity in pain-related regions including the pre-supplementary motor area, brainstem (periaqueductal gray) and dissociable parts of caudal and rostral ACC. In particular, when the patient reported experiencing pain, there was increased activity in different regions of ACC compared to when he experienced pain relief. We were also able to demonstrate long-term functional brain changes as a result of continuous DBS over one year, leading to specific changes in the activity in dissociable regions of caudal and rostral ACC. These results broaden our understanding of the underlying mechanisms of DBS in the human brain. PMID:22675503

Comparison of current distributions in electroconvulsive therapy and transcranial magnetic stimulation

NASA Astrophysics Data System (ADS)

Sekino, Masaki; Ueno, Shoogo

2002-05-01

We compared current density distributions in electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) by numerical calculations. The model consisted of an air region and three types of tissues with different conductivities representing the brain, the skull, and the scalp. In the ECT model, electric currents were applied through electrodes with a voltage of 100 V. In the TMS model, a figure-eight coil (6 cm diameter per coil) was placed on the vertex of the head model. An alternating current with a peak intensity of 3.0 kA and a frequency of 4.2 kHz was applied to the coil. The maximum current densities inside the brain in ECT (bilateral electrode position) and TMS were 234 and 322 A/m2, respectively. The results indicate that magnetic stimulators can generate comparable current densities to ECT. While the skull significantly affected current distributions in ECT, TMS efficiently induced eddy currents in the brain. In addition, TMS is more beneficial than ECT because the localized current distribution reduces the risk of adverse side effects.

A Low Power Micro Deep Brain Stimulation Device for Murine Preclinical Research.

PubMed

Kouzani, Abbas Z; Abulseoud, Osama A; Tye, Susannah J; Hosain, M D Kamal; Berk, Michael

2013-01-01

Deep brain stimulation has emerged as an effective medical procedure that has therapeutic efficacy in a number of neuropsychiatric disorders. Preclinical research involving laboratory animals is being conducted to study the principles, mechanisms, and therapeutic effects of deep brain stimulation. A bottleneck is, however, the lack of deep brain stimulation devices that enable long term brain stimulation in freely moving laboratory animals. Most of the existing devices employ complex circuitry, and are thus bulky. These devices are usually connected to the electrode that is implanted into the animal brain using long fixed wires. In long term behavioral trials, however, laboratory animals often need to continuously receive brain stimulation for days without interruption, which is difficult with existing technology. This paper presents a low power and lightweight portable microdeep brain stimulation device for laboratory animals. Three different configurations of the device are presented as follows: 1) single piece head mountable; 2) single piece back mountable; and 3) two piece back mountable. The device can be easily carried by the animal during the course of a clinical trial, and that it can produce non-stop stimulation current pulses of desired characteristics for over 12 days on a single battery. It employs passive charge balancing to minimize undesirable effects on the target tissue. The results of bench, in-vitro, and in-vivo tests to evaluate the performance of the device are presented.

Bio-heat transfer model of deep brain stimulation-induced temperature changes

NASA Astrophysics Data System (ADS)

Elwassif, Maged M.; Kong, Qingjun; Vazquez, Maribel; Bikson, Marom

2006-12-01

There is a growing interest in the use of chronic deep brain stimulation (DBS) for the treatment of medically refractory movement disorders and other neurological and psychiatric conditions. Fundamental questions remain about the physiologic effects of DBS. Previous basic research studies have focused on the direct polarization of neuronal membranes by electrical stimulation. The goal of this paper is to provide information on the thermal effects of DBS using finite element models to investigate the magnitude and spatial distribution of DBS-induced temperature changes. The parameters investigated include stimulation waveform, lead selection, brain tissue electrical and thermal conductivities, blood perfusion, metabolic heat generation during the stimulation and lead thermal conductivity/heat dissipation through the electrode. Our results show that clinical DBS protocols will increase the temperature of surrounding tissue by up to 0.8 °C depending on stimulation/tissue parameters.

Increasing propensity to mind-wander with transcranial direct current stimulation

PubMed Central

Axelrod, Vadim; Rees, Geraint; Lavidor, Michal; Bar, Moshe

2015-01-01

Humans mind-wander quite intensely. Mind wandering is markedly different from other cognitive behaviors because it is spontaneous, self-generated, and inwardly directed (inner thoughts). However, can such an internal and intimate mental function also be modulated externally by means of brain stimulation? Addressing this question could also help identify the neural correlates of mind wandering in a causal manner, in contrast to the correlational methods used previously (primarily functional MRI). In our study, participants performed a monotonous task while we periodically sampled their thoughts to assess mind wandering. Concurrently, we applied transcranial direct current stimulation (tDCS). We found that stimulation of the frontal lobes [anode electrode at the left dorsolateral prefrontal cortex (DLPFC), cathode electrode at the right supraorbital area], but not of the occipital cortex or sham stimulation, increased the propensity to mind-wander. These results demonstrate for the first time, to our knowledge, that mind wandering can be enhanced externally using brain stimulation, and that the frontal lobes play a causal role in mind-wandering behavior. These results also suggest that the executive control network associated with the DLPFC might be an integral part of mind-wandering neural machinery. PMID:25691738

Increasing propensity to mind-wander with transcranial direct current stimulation.

PubMed

Axelrod, Vadim; Rees, Geraint; Lavidor, Michal; Bar, Moshe

2015-03-17

Humans mind-wander quite intensely. Mind wandering is markedly different from other cognitive behaviors because it is spontaneous, self-generated, and inwardly directed (inner thoughts). However, can such an internal and intimate mental function also be modulated externally by means of brain stimulation? Addressing this question could also help identify the neural correlates of mind wandering in a causal manner, in contrast to the correlational methods used previously (primarily functional MRI). In our study, participants performed a monotonous task while we periodically sampled their thoughts to assess mind wandering. Concurrently, we applied transcranial direct current stimulation (tDCS). We found that stimulation of the frontal lobes [anode electrode at the left dorsolateral prefrontal cortex (DLPFC), cathode electrode at the right supraorbital area], but not of the occipital cortex or sham stimulation, increased the propensity to mind-wander. These results demonstrate for the first time, to our knowledge, that mind wandering can be enhanced externally using brain stimulation, and that the frontal lobes play a causal role in mind-wandering behavior. These results also suggest that the executive control network associated with the DLPFC might be an integral part of mind-wandering neural machinery.

Mechanisms of electrode induced injury. Part 2: Clinical experience.

PubMed

Patterson, Terry; Stecker, Mark M; Netherton, Brett L

2007-06-01

In the previous paper in this series, basic mechanisms of electrode related injuries were discussed. In this paper, the discussion begins with some of the clinical aspects of burns. This is followed by a summary of the clinical literature on injuries produced by surface and subdermal electrodes. This clinical literature demonstrates that most electrode burns are related to the presence of high frequency electric fields (RF) created either by an electrosurgical unit or a magnetic resonance imaging (MRI) scanner. A smaller number of lesions are produced by low current, long duration direct current (DC) stimulation and during high current stimulation such as defibrillation. A discussion of the clinical complications from indwelling intracranial electrodes centers on electrodes placed for deep brain stimulation (DBS) that are currently used therapeutically in a wide array of neurologic disorders. The probability of considering a post-implant MRI scan is high and the safety of such scans is the focus of discussion. A very small number of adverse incidents have indicated a downward revision in the specific absorption rate recommendations for MRI examination with those patients who present with indwelling DBS leads and internal pulse generators. Continued vigilance when any type of electrode is used is important.

Optimized beamforming for simultaneous MEG and intracranial local field potential recordings in deep brain stimulation patients.

PubMed

Litvak, Vladimir; Eusebio, Alexandre; Jha, Ashwani; Oostenveld, Robert; Barnes, Gareth R; Penny, William D; Zrinzo, Ludvic; Hariz, Marwan I; Limousin, Patricia; Friston, Karl J; Brown, Peter

2010-05-01

Insight into how brain structures interact is critical for understanding the principles of functional brain architectures and may lead to better diagnosis and therapy for neuropsychiatric disorders. We recorded, simultaneously, magnetoencephalographic (MEG) signals and subcortical local field potentials (LFP) in a Parkinson's disease (PD) patient with bilateral deep brain stimulation (DBS) electrodes in the subthalamic nucleus (STN). These recordings offer a unique opportunity to characterize interactions between the subcortical structures and the neocortex. However, high-amplitude artefacts appeared in the MEG. These artefacts originated from the percutaneous extension wire, rather than from the actual DBS electrode and were locked to the heart beat. In this work, we show that MEG beamforming is capable of suppressing these artefacts and quantify the optimal regularization required. We demonstrate how beamforming makes it possible to localize cortical regions whose activity is coherent with the STN-LFP, extract artefact-free virtual electrode time-series from regions of interest and localize cortical areas exhibiting specific task-related power changes. This furnishes results that are consistent with previously reported results using artefact-free MEG data. Our findings demonstrate that physiologically meaningful information can be extracted from heavily contaminated MEG signals and pave the way for further analysis of combined MEG-LFP recordings in DBS patients. 2009 Elsevier Inc. All rights reserved.

Stretchable Transparent Electrode Arrays for Simultaneous Electrical and Optical Interrogation of Neural Circuits in Vivo.

PubMed

Zhang, Jing; Liu, Xiaojun; Xu, Wenjing; Luo, Wenhan; Li, Ming; Chu, Fangbing; Xu, Lu; Cao, Anyuan; Guan, Jisong; Tang, Shiming; Duan, Xiaojie

2018-05-09

Recent developments of transparent electrode arrays provide a unique capability for simultaneous optical and electrical interrogation of neural circuits in the brain. However, none of these electrode arrays possess the stretchability highly desired for interfacing with mechanically active neural systems, such as the brain under injury, the spinal cord, and the peripheral nervous system (PNS). Here, we report a stretchable transparent electrode array from carbon nanotube (CNT) web-like thin films that retains excellent electrochemical performance and broad-band optical transparency under stretching and is highly durable under cyclic stretching deformation. We show that the CNT electrodes record well-defined neuronal response signals with negligible light-induced artifacts from cortical surfaces under optogenetic stimulation. Simultaneous two-photon calcium imaging through the transparent CNT electrodes from cortical surfaces of GCaMP-expressing mice with epilepsy shows individual activated neurons in brain regions from which the concurrent electrical recording is taken, thus providing complementary cellular information in addition to the high-temporal-resolution electrical recording. Notably, the studies on rats show that the CNT electrodes remain operational during and after brain contusion that involves the rapid deformation of both the electrode array and brain tissue. This enables real-time, continuous electrophysiological monitoring of cortical activity under traumatic brain injury. These results highlight the potential application of the stretchable transparent CNT electrode arrays in combining electrical and optical modalities to study neural circuits, especially under mechanically active conditions, which could potentially provide important new insights into the local circuit dynamics of the spinal cord and PNS as well as the mechanism underlying traumatic injuries of the nervous system.

Vertically aligned carbon nanofiber as nano-neuron interface for monitoring neural function.

PubMed

Yu, Zhe; McKnight, Timothy E; Ericson, M Nance; Melechko, Anatoli V; Simpson, Michael L; Morrison, Barclay

2012-05-01

Neural chips, which are capable of simultaneous multisite neural recording and stimulation, have been used to detect and modulate neural activity for almost thirty years. As neural interfaces, neural chips provide dynamic functional information for neural decoding and neural control. By improving sensitivity and spatial resolution, nano-scale electrodes may revolutionize neural detection and modulation at cellular and molecular levels as nano-neuron interfaces. We developed a carbon-nanofiber neural chip with lithographically defined arrays of vertically aligned carbon nanofiber electrodes and demonstrated its capability of both stimulating and monitoring electrophysiological signals from brain tissues in vitro and monitoring dynamic information of neuroplasticity. This novel nano-neuron interface may potentially serve as a precise, informative, biocompatible, and dual-mode neural interface for monitoring of both neuroelectrical and neurochemical activity at the single-cell level and even inside the cell. The authors demonstrate the utility of a neural chip with lithographically defined arrays of vertically aligned carbon nanofiber electrodes. The new device can be used to stimulate and/or monitor signals from brain tissue in vitro and for monitoring dynamic information of neuroplasticity both intracellularly and at the single cell level including neuroelectrical and neurochemical activities. Copyright © 2012 Elsevier Inc. All rights reserved.

Multi-electrode stimulation in somatosensory cortex increases probability of detection

NASA Astrophysics Data System (ADS)

Zaaimi, Boubker; Ruiz-Torres, Ricardo; Solla, Sara A.; Miller, Lee E.

2013-10-01

Objective. Brain machine interfaces (BMIs) that decode control signals from motor cortex have developed tremendously in the past decade, but virtually all rely exclusively on vision to provide feedback. There is now increasing interest in developing an afferent interface to replace natural somatosensation, much as the cochlear implant has done for the sense of hearing. Preliminary experiments toward a somatosensory neuroprosthesis have mostly addressed the sense of touch, but proprioception, the sense of limb position and movement, is also critical for the control of movement. However, proprioceptive areas of cortex lack the precise somatotopy of tactile areas. We showed previously that there is only a weak tendency for neighboring neurons in area 2 to signal similar directions of hand movement. Consequently, stimulation with the relatively large currents used in many studies is likely to activate a rather heterogeneous set of neurons. Approach. Here, we have compared the effect of single-electrode stimulation at subthreshold levels to the effect of stimulating as many as seven electrodes in combination. Main results. We found a mean enhancement in the sensitivity to the stimulus (d‧) of 0.17 for pairs compared to individual electrodes (an increase of roughly 30%), and an increase of 2.5 for groups of seven electrodes (260%). Significance. We propose that a proprioceptive interface made up of several hundred electrodes may yield safer, more effective sensation than a BMI using fewer electrodes and larger currents.

Asleep Deep Brain Stimulation Reduces Incidence of Intracranial Air during Electrode Implantation.

PubMed

Ko, Andrew L; Magown, Philippe; Ozpinar, Alp; Hamzaoglu, Vural; Burchiel, Kim J

2018-05-30

Asleep deep brain stimulation (aDBS) implantation replaces microelectrode recording for image-guided implantation, shortening the operative time and reducing cerebrospinal fluid egress. This may decrease pneumocephalus, thus decreasing brain shift during implantation. To compare the incidence and volume of pneumocephalus during awake (wkDBS) and aDBS procedures. A retrospective review of bilateral DBS cases performed at Oregon Health & Science University from 2009 to 2017 was undertaken. Postimplantation imaging was reviewed to determine the presence and volume of intracranial air and measure cortical brain shift. Among 371 patients, pneumocephalus was noted in 66% of wkDBS and 15.6% of aDBS. The average volume of air was significantly higher in wkDBS than aDBS (8.0 vs. 1.8 mL). Volumes of air greater than 7 mL, which have previously been linked to brain shift, occurred significantly more frequently in wkDBS than aDBS (34 vs 5.6%). wkDBS resulted in significantly larger cortical brain shifts (5.8 vs. 1.2 mm). We show that aDBS reduces the incidence of intracranial air, larger air volumes, and cortical brain shift. Large volumes of intracranial air have been correlated to shifting of brain structures during DBS procedures, a variable that could impact accuracy of electrode placement. © 2018 S. Karger AG, Basel.

Transcranial current stimulation focality using disc and ring electrode configurations: FEM analysis

NASA Astrophysics Data System (ADS)

Datta, Abhishek; Elwassif, Maged; Battaglia, Fortunato; Bikson, Marom

2008-06-01

We calculated the electric fields induced in the brain during transcranial current stimulation (TCS) using a finite-element concentric spheres human head model. A range of disc electrode configurations were simulated: (1) distant-bipolar; (2) adjacent-bipolar; (3) tripolar; and three ring designs, (4) belt, (5) concentric ring, and (6) double concentric ring. We compared the focality of each configuration targeting cortical structures oriented normal to the surface ('surface-radial' and 'cross-section radial'), cortical structures oriented along the brain surface ('surface-tangential' and 'cross-section tangential') and non-oriented cortical surface structures ('surface-magnitude' and 'cross-section magnitude'). For surface-radial fields, we further considered the 'polarity' of modulation (e.g. superficial cortical neuron soma hyper/depolarizing). The distant-bipolar configuration, which is comparable with commonly used TCS protocols, resulted in diffuse (un-focal) modulation with bi-directional radial modulation under each electrode and tangential modulation between electrodes. Increasing the proximity of the two electrodes (adjacent-bipolar electrode configuration) increased focality, at the cost of more surface current. At similar electrode distances, the tripolar-electrodes configuration produced comparable peak focality, but reduced radial bi-directionality. The concentric-ring configuration resulted in the highest spatial focality and uni-directional radial modulation, at the expense of increased total surface current. Changing ring dimensions, or use of two concentric rings, allow titration of this balance. The concentric-ring design may thus provide an optimized configuration for targeted modulation of superficial cortical neurons.

A Strange Case of Downward Displacement of a Deep Brain Stimulation Electrode 10 Years Following Implantation: The Gliding Movement of Snakes Theory.

PubMed

Iacopino, Domenico Gerardo; Maugeri, Rosario; Giugno, Antonella; Giller, Cole A

2015-08-01

Despite the best efforts to ensure stereotactic precision, deep brain stimulation (DBS) electrodes can wander from their intended position after implantation. We report a case of downward electrode migration 10 years following successful implantation in a patient with Parkinson disease. A 53-year-old man with Parkinson disease underwent bilateral implantation of DBS electrodes connected to a subclavicular 2-channel pulse generator. The generator was replaced 7 years later, and a computed tomography (CT) scan confirmed the correct position of both leads. The patient developed a gradual worsening affecting his right side 3 years later, 10 years after the original implantation. A CT scan revealed displacement of the left electrode inferiorly into the pons. The new CT scans and the CT scans obtained immediately after the implantation were merged within a stereotactic planning workstation (Brainlab). Comparing the CT scans, the distal end of the electrode was in the same position, the proximal tip being significantly more inferior. The size and configuration of the coiled portions of the electrode had not changed. At implantation, the length was 27.7 cm; after 10 years, the length was 30.6 cm. These data suggests that the electrode had been stretched into its new position rather than pushed. Clinicians evaluating patients with a delayed worsening should be aware of this rare event. Copyright © 2015 Elsevier Inc. All rights reserved.

Deep brain stimulation for movement disorders.

PubMed

Thevathasan, Wesley; Gregory, Ralph

2010-02-01

Deep brain stimulation is now considered a routine treatment option for selected patients with advanced Parkinson's disease, primary segmental and generalised dystonia, and essential tremor. The neurosurgeon is responsible for the accurate and safe placement of the electrodes and the neurologist for the careful selection of patients and titration of medication against the effects of stimulation. A multidisciplinary team approach involving specialist nurses, neuropsychologists and neurophysiologists is required for a successful outcome. In this article we will summarise the key points in patient selection, provide an overview of the surgical technique, and discuss the beneficial and adverse outcomes that can occur.

Safety of externally stimulated intracranial electrodes during functional MRI at 1.5T.

PubMed

Bhattacharyya, Pallab K; Mullin, Jeffery; Lee, Bryan S; Gonzalez-Martinez, Jorge A; Jones, Stephen E

2017-05-01

Surgical resection of the epileptogenic zone (EZ) is a potential cure for medically refractory focal epilepsy. Proper identification of the EZ is essential for such resection. Synergistic application of functional magnetic resonance imaging (fMRI) simultaneously with stimulation of a single externalized intracranial stereotactic EEG (SEEG) electrode has the potential to improve identification of the EZ. While most EEG-fMRI studies use the electrodes passively to record electrical activity, it is possible to stimulate the brain using the electrodes by connecting them with conducting cables to the stimulation hardware. In this study, we investigated the effect of MRI-induced heating on a single SEEG electrode and its sensitivity to geometry, configuration, and associated connections required for the stimulation. The temperature increase of a single electrode embedded within a gel phantom and connected to an external stimulation system was measured during 1.5T MRI scans using adjacent fluoroptic temperature sensors. A receive-only split-array head coil and a transmit-receive head coil were used for testing. Sequences included a standard localizer, T1-weighted axial fast low-angle shot (FLASH), gradient echo-planar imaging (GE-EPI) axial fMRI, and a high specific absorption rate T2-weighted turbo spin-echo (TSE) axial scan. Variations of the electrode location and connecting cable configuration were tested. No unacceptable heating was observed with the standard sequences used for evaluation of the EZ. Considerable heating (up to 14°C) was observed with the TSE sequence, which is not used clinically. The temperature increase was insignificant (<0.05°C) for electrode contacts closest to the isocenter and connecting cables lying along the isocenter, and varied with configurations of the connecting cable assembly. Simultaneous intracranial electrode stimulation during fMRI using an externalized stimulation system may be safe with strict adherence to settings tested prior to the fMRI. Localizer, FLASH, and GE-EPI fMRI may be safely performed in patients with a single SEEG electrode following the configurations tested in this study, but high SAR TSE scans should not be performed in these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Modeling deep brain stimulation: point source approximation versus realistic representation of the electrode

NASA Astrophysics Data System (ADS)

Zhang, Tianhe C.; Grill, Warren M.

2010-12-01

Deep brain stimulation (DBS) has emerged as an effective treatment for movement disorders; however, the fundamental mechanisms by which DBS works are not well understood. Computational models of DBS can provide insights into these fundamental mechanisms and typically require two steps: calculation of the electrical potentials generated by DBS and, subsequently, determination of the effects of the extracellular potentials on neurons. The objective of this study was to assess the validity of using a point source electrode to approximate the DBS electrode when calculating the thresholds and spatial distribution of activation of a surrounding population of model neurons in response to monopolar DBS. Extracellular potentials in a homogenous isotropic volume conductor were calculated using either a point current source or a geometrically accurate finite element model of the Medtronic DBS 3389 lead. These extracellular potentials were coupled to populations of model axons, and thresholds and spatial distributions were determined for different electrode geometries and axon orientations. Median threshold differences between DBS and point source electrodes for individual axons varied between -20.5% and 9.5% across all orientations, monopolar polarities and electrode geometries utilizing the DBS 3389 electrode. Differences in the percentage of axons activated at a given amplitude by the point source electrode and the DBS electrode were between -9.0% and 12.6% across all monopolar configurations tested. The differences in activation between the DBS and point source electrodes occurred primarily in regions close to conductor-insulator interfaces and around the insulating tip of the DBS electrode. The robustness of the point source approximation in modeling several special cases—tissue anisotropy, a long active electrode and bipolar stimulation—was also examined. Under the conditions considered, the point source was shown to be a valid approximation for predicting excitation of populations of neurons in response to DBS.

From Nose to Brain: Un-Sensed Electrical Currents Applied in the Nose Alter Activity in Deep Brain Structures

PubMed Central

Weiss, Tali; Shushan, Sagit; Ravia, Aharon; Hahamy, Avital; Secundo, Lavi; Weissbrod, Aharon; Ben-Yakov, Aya; Holtzman, Yael; Cohen-Atsmoni, Smadar; Roth, Yehudah; Sobel, Noam

2016-01-01

Rules linking patterns of olfactory receptor neuron activation in the nose to activity patterns in the brain and ensuing odor perception remain poorly understood. Artificially stimulating olfactory neurons with electrical currents and measuring ensuing perception may uncover these rules. We therefore inserted an electrode into the nose of 50 human volunteers and applied various currents for about an hour in each case. This induced assorted non-olfactory sensations but never once the perception of odor. To validate contact with the olfactory path, we used functional magnetic resonance imaging to measure resting-state brain activity in 18 subjects before and after un-sensed stimulation. We observed stimulation-induced neural decorrelation specifically in primary olfactory cortex, implying contact with the olfactory path. These results suggest that indiscriminate olfactory activation does not equate with odor perception. Moreover, this effort serendipitously uncovered a novel path for minimally invasive brain stimulation through the nose. PMID:27591145

[Neurological and technical aspects of deep brain stimulation].

PubMed

Voges, J; Krauss, J K

2010-06-01

Deep brain stimulation (DBS) is an important component of the therapy of movement disorders and has almost completely replaced high-frequency coagulation of brain tissue in stereotactic neurosurgery. Despite the functional efficacy of DBS, which in parts is documented on the highest evidence level, the underlying mechanisms are still not completely understood. According to the current state of knowledge electrophysiological and functional data give evidence that high-frequency DBS has an inhibitory effect around the stimulation electrode whilst at the same time axons entering or leaving the stimulated brain area are excited leading to modulation of neuronal networks. The latter effect modifies pathological discharges of neurons in key structures of the basal ganglia network (e.g. irregular bursting activity, oscillations or synchronization) which are found in particular movement disorders such as Parkinson' s disease or dystonia. The introduction of technical standards, such as the integration of high resolution MRI into computer-assisted treatment planning, in combination with special treatment planning software have contributed significantly to the reduction of severe surgical complications (frequency of intracranial hemorrhaging 1-3%) in recent years. Future developments will address the modification of hardware components of the stimulation system, the evaluation of new brain target areas, the simultaneous stimulation of different brain areas and the assessment of different stimulation paradigms (high-frequency vs low-frequency DBS).

State of the Art: Novel Applications for Cortical Stimulation.

PubMed

De Ridder, Dirk; Perera, Sanjaya; Vanneste, Sven

2017-04-01

Electrical stimulation via implanted electrodes that overlie the cortex of the brain is an upcoming neurosurgical technique that was hindered for a long time by insufficient knowledge of how the brain functions in a dynamic, physiological, and pathological way, as well as by technological limitations of the implantable stimulation devices. This paper provides an overview of cortex stimulation via implantable devices and introduces future possibilities to improve cortex stimulation. Cortex stimulation was initially used preoperatively as a technique to localize functions in the brain and only later evolved into a treatment technique. It was first used for pain, but more recently a multitude of pathologies are being targeted by cortex stimulation. These disorders are being treated by stimulating different cortical areas of the brain. Risks and complications are essentially similar to those related to deep brain stimulation and predominantly include haemorrhage, seizures, infection, and hardware failures. For cortex stimulation to fully mature, further technological development is required to predict its outcomes and improve stimulation designs. This includes the development of network science-based functional connectivity approaches, genetic analyses, development of navigated high definition transcranial alternating current stimulation, and development of pseudorandom stimulation designs for preventing habituation. In conclusion, cortex stimulation is a nascent but very promising approach to treating a variety of diseases, but requires further technological development for predicting outcomes, such as network science based functional connectivity approaches, genetic analyses, development of navigated transcranial electrical stimulation, and development of pseudorandom stimulation designs for preventing habituation. © 2017 International Neuromodulation Society.

A tripolar current-steering stimulator ASIC for field shaping in deep brain stimulation.

PubMed

Valente, Virgilio; Demosthenous, Andreas; Bayford, Richard

2012-06-01

A significant problem with clinical deep brain stimulation (DBS) is the high variability of its efficacy and the frequency of side effects, related to the spreading of current beyond the anatomical target area. This is the result of the lack of control that current DBS systems offer on the shaping of the electric potential distribution around the electrode. This paper presents a stimulator ASIC with a tripolar current-steering output stage, aiming at achieving more selectivity and field shaping than current DBS systems. The ASIC was fabricated in a 0.35-μ m CMOS technology occupying a core area of 0.71 mm(2). It consists of three current sourcing/sinking channels. It is capable of generating square and exponential-decay biphasic current pulses with five different time constants up to 28 ms and delivering up to 1.85 mA of cathodic current, in steps of 4 μA, from a 12 V power supply. Field shaping was validated by mapping the potential distribution when injecting current pulses through a multicontact DBS electrode in saline.

Optimal use of EEG recordings to target active brain areas with transcranial electrical stimulation.

PubMed

Dmochowski, Jacek P; Koessler, Laurent; Norcia, Anthony M; Bikson, Marom; Parra, Lucas C

2017-08-15

To demonstrate causal relationships between brain and behavior, investigators would like to guide brain stimulation using measurements of neural activity. Particularly promising in this context are electroencephalography (EEG) and transcranial electrical stimulation (TES), as they are linked by a reciprocity principle which, despite being known for decades, has not led to a formalism for relating EEG recordings to optimal stimulation parameters. Here we derive a closed-form expression for the TES configuration that optimally stimulates (i.e., targets) the sources of recorded EEG, without making assumptions about source location or distribution. We also derive a duality between TES targeting and EEG source localization, and demonstrate that in cases where source localization fails, so does the proposed targeting. Numerical simulations with multiple head models confirm these theoretical predictions and quantify the achieved stimulation in terms of focality and intensity. We show that constraining the stimulation currents automatically selects optimal montages that involve only a few (4-7) electrodes, with only incremental loss in performance when targeting focal activations. The proposed technique allows brain scientists and clinicians to rationally target the sources of observed EEG and thus overcomes a major obstacle to the realization of individualized or closed-loop brain stimulation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Optimal use of EEG recordings to target active brain areas with transcranial electrical stimulation

PubMed Central

Dmochowski, Jacek P.; Koessler, Laurent; Norcia, Anthony M.; Bikson, Marom; Parra, Lucas C.

2018-01-01

To demonstrate causal relationships between brain and behavior, investigators would like to guide brain stimulation using measurements of neural activity. Particularly promising in this context are electroencephalography (EEG) and transcranial electrical stimulation (TES), as they are linked by a reciprocity principle which, despite being known for decades, has not led to a formalism for relating EEG recordings to optimal stimulation parameters. Here we derive a closed-form expression for the TES configuration that optimally stimulates (i.e., targets) the sources of recorded EEG, without making assumptions about source location or distribution. We also derive a duality between TES targeting and EEG source localization, and demonstrate that in cases where source localization fails, so does the proposed targeting. Numerical simulations with multiple head models confirm these theoretical predictions and quantify the achieved stimulation in terms of focality and intensity. We show that constraining the stimulation currents automatically selects optimal montages that involve only a few (4–7) electrodes, with only incremental loss in performance when targeting focal activations. The proposed technique allows brain scientists and clinicians to rationally target the sources of observed EEG and thus overcomes a major obstacle to the realization of individualized or closed-loop brain stimulation. PMID:28578130

[Twiddler's syndrome in a patient with obsessive-compulsive disorder treated with deep brain stimulation].

PubMed

Moliz, Nicolás; Katati, Majed J; Iañez, Benjamín; García, Asunción; Yagui, Eskandar; Horcajadas, Ángel

2015-01-01

Twiddler's syndrome is a rare complication associated with implantable electrical stimulation devices. First described in a patient with a pacemaker, it is a known complication in the field of cardiology. However, it is not so recognised in the world of neurosurgery, in which it has been described in relation to deep brain stimulation (DBS) devices. Characterised by manipulating either consciously or unconsciously the generator of such devices, which causes it to rotate on itself, the syndrome causes the coiling of the wiring of these systems and can lead to their rupture or the displacement of intracranial electrodes. We describe a case of twiddler's syndrome in a patient treated with DBS for obsessive-compulsive disorder, in which clinical deterioration presented after a good initial response. Control radiographs revealed rotation of the wiring system and displacement of the intracranial electrodes. Copyright © 2013 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

A cognitive neuroprosthetic that uses cortical stimulation for somatosensory feedback.

PubMed

Klaes, Christian; Shi, Ying; Kellis, Spencer; Minxha, Juri; Revechkis, Boris; Andersen, Richard A

2014-10-01

Present day cortical brain-machine interfaces (BMIs) have made impressive advances using decoded brain signals to control extracorporeal devices. Although BMIs are used in a closed-loop fashion, sensory feedback typically is visual only. However medical case studies have shown that the loss of somesthesis in a limb greatly reduces the agility of the limb even when visual feedback is available. To overcome this limitation, this study tested a closed-loop BMI that utilizes intracortical microstimulation to provide 'tactile' sensation to a non-human primate. Using stimulation electrodes in Brodmann area 1 of somatosensory cortex (BA1) and recording electrodes in the anterior intraparietal area, the parietal reach region and dorsal area 5 (area 5d), it was found that this form of feedback can be used in BMI tasks. Providing somatosensory feedback has the poyential to greatly improve the performance of cognitive neuroprostheses especially for fine control and object manipulation. Adding stimulation to a BMI system could therefore improve the quality of life for severely paralyzed patients.

Toward a noninvasive automatic seizure control system in rats with transcranial focal stimulations via tripolar concentric ring electrodes

PubMed Central

Makeyev, Oleksandr; Liu, Xiang; Luna-Munguía, Hiram; Rogel-Salazar, Gabriela; Mucio-Ramirez, Samuel; Liu, Yuhong; Sun, Yan L.; Kay, Steven M.; Besio, Walter G.

2012-01-01

Epilepsy affects approximately one percent of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We are developing a noninvasive, or minimally invasive, transcranial focal electrical stimulation system through our novel tripolar concentric ring electrodes to control seizures. In this study we demonstrate feasibility of an automatic seizure control system in rats with pentylenetetrazole-induced seizures through single and multiple stimulations. These stimulations are automatically triggered by a real-time electrographic seizure activity detector based on a disjunctive combination of detections from a cumulative sum algorithm and a generalized likelihood ratio test. An average seizure onset detection accuracy of 76.14% was obtained for the test set (n = 13). Detection of electrographic seizure activity was accomplished in advance of the early behavioral seizure activity in 76.92% of the cases. Automatically triggered stimulation significantly (p = 0.001) reduced the electrographic seizure activity power in the once stimulated group compared to controls in 70% of the cases. To the best of our knowledge this is the first closed-loop automatic seizure control system based on noninvasive electrical brain stimulation using tripolar concentric ring electrode electrographic seizure activity as feedback. PMID:22772373

Toward a noninvasive automatic seizure control system in rats with transcranial focal stimulations via tripolar concentric ring electrodes.

PubMed

Makeyev, Oleksandr; Liu, Xiang; Luna-Munguía, Hiram; Rogel-Salazar, Gabriela; Mucio-Ramirez, Samuel; Liu, Yuhong; Sun, Yan L; Kay, Steven M; Besio, Walter G

2012-07-01

Epilepsy affects approximately 1% of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We are developing a noninvasive, or minimally invasive, transcranial focal electrical stimulation system through our novel tripolar concentric ring electrodes to control seizures. In this study, we demonstrate feasibility of an automatic seizure control system in rats with pentylenetetrazole-induced seizures through single and multiple stimulations. These stimulations are automatically triggered by a real-time electrographic seizure activity detector based on a disjunctive combination of detections from a cumulative sum algorithm and a generalized likelihood ratio test. An average seizure onset detection accuracy of 76.14% was obtained for the test set (n = 13). Detection of electrographic seizure activity was accomplished in advance of the early behavioral seizure activity in 76.92% of the cases. Automatically triggered stimulation significantly (p = 0.001) reduced the electrographic seizure activity power in the once stimulated group compared to controls in 70% of the cases. To the best of our knowledge this is the first closed-loop automatic seizure control system based on noninvasive electrical brain stimulation using tripolar concentric ring electrode electrographic seizure activity as feedback.

Ultrasoft microwire neural electrodes improve chronic tissue integration

PubMed Central

Du, Zhanhong Jeff; Kolarcik, Christi L.; Kozai, Takashi D.Y.; Luebben, Silvia D.; Sapp, Shawn A.; Zheng, Xin Sally; Nabity, James A.; Cui, X. Tracy

2017-01-01

Chronically implanted neural multi-electrode arrays (MEA) are an essential technology for recording electrical signals from neurons and/or modulating neural activity through stimulation. However, current MEAs, regardless of the type, elicit an inflammatory response that ultimately leads to device failure. Traditionally, rigid materials like tungsten and silicon have been employed to interface with the relatively soft neural tissue. The large stiffness mismatch is thought to exacerbate the inflammatory response. In order to minimize the disparity between the device and the brain, we fabricated novel ultrasoft electrodes consisting of elastomers and conducting polymers with mechanical properties much more similar to those of brain tissue than previous neural implants. In this study, these ultrasoft microelectrodes were inserted and released using a stainless steel shuttle with polyethyleneglycol (PEG) glue. The implanted microwires showed functionality in acute neural stimulation. When implanted for 1 or 8 weeks, the novel soft implants demonstrated significantly reduced inflammatory tissue response at week 8 compared to tungsten wires of similar dimension and surface chemistry. Furthermore, a higher degree of cell body distortion was found next to the tungsten implants compared to the polymer implants. Our results support the use of these novel ultrasoft electrodes for long term neural implants. PMID:28185910

Miniaturized neural interfaces and implants

NASA Astrophysics Data System (ADS)

Stieglitz, Thomas; Boretius, Tim; Ordonez, Juan; Hassler, Christina; Henle, Christian; Meier, Wolfgang; Plachta, Dennis T. T.; Schuettler, Martin

2012-03-01

Neural prostheses are technical systems that interface nerves to treat the symptoms of neurological diseases and to restore sensory of motor functions of the body. Success stories have been written with the cochlear implant to restore hearing, with spinal cord stimulators to treat chronic pain as well as urge incontinence, and with deep brain stimulators in patients suffering from Parkinson's disease. Highly complex neural implants for novel medical applications can be miniaturized either by means of precision mechanics technologies using known and established materials for electrodes, cables, and hermetic packages or by applying microsystems technologies. Examples for both approaches will be introduced and discussed. Electrode arrays for recording of electrocorticograms during presurgical epilepsy diagnosis have been manufactured using approved materials and a marking laser to achieve an integration density that is adequate in the context of brain machine interfaces, e.g. on the motor cortex. Microtechnologies have to be used for further miniaturization to develop polymer-based flexible and light weighted electrode arrays to interface the peripheral and central nervous system. Polyimide as substrate and insulation material will be discussed as well as several application examples for nerve interfaces like cuffs, filament like electrodes and large arrays for subdural implantation.

Getting signals into the brain: visual prosthetics through thalamic microstimulation.

PubMed

Pezaris, John S; Eskandar, Emad N

2009-07-01

Common causes of blindness are diseases that affect the ocular structures, such as glaucoma, retinitis pigmentosa, and macular degeneration, rendering the eyes no longer sensitive to light. The visual pathway, however, as a predominantly central structure, is largely spared in these cases. It is thus widely thought that a device-based prosthetic approach to restoration of visual function will be effective and will enjoy similar success as cochlear implants have for restoration of auditory function. In this article the authors review the potential locations for stimulation electrode placement for visual prostheses, assessing the anatomical and functional advantages and disadvantages of each. Of particular interest to the neurosurgical community is placement of deep brain stimulating electrodes in thalamic structures that has shown substantial promise in an animal model. The theory of operation of visual prostheses is discussed, along with a review of the current state of knowledge. Finally, the visual prosthesis is proposed as a model for a general high-fidelity machine-brain interface.

Magnetic resonance and computed tomography image fusion technology in patients with Parkinson's disease after deep brain stimulation.

PubMed

Xia, Jun; He, Pin; Cai, Xiaodong; Zhang, Doudou; Xie, Ni

2017-10-15

Electrode position after deep brain stimulation (DBS) for Parkinson's disease (PD) needs to be confirmed, but there are concerns about the risk of postoperative magnetic resonance imaging (MRI) after DBS. These issues could be avoided by fusion images obtained from preoperative MRI and postoperative computed tomography (CT). This study aimed to investigate image fusion technology for displaying the position of the electrodes compared with postoperative MRI. This was a retrospective study of 32 patients with PD treated with bilateral subthalamic nucleus (STN) DBS between April 2015 and March 2016. The postoperative (same day) CT and preoperative MRI were fused using the Elekta Leksell 10.1 planning workstation (Elekta Instruments, Stockholm, Sweden). The position of the electrodes was compared between the fusion images and postoperative 1-2-week MRI. The position of the electrodes was highly correlated between the fusion and postoperative MRI (all r between 0.865 and 0.996; all P<0.001). The differences of the left electrode position in the lateral and vertical planes was significantly different between the two methods (0.30 and 0.24mm, respectively, both P<0.05), but there were no significant differences for the other electrode and planes (all P>0.05). The position of the electrodes was highly correlated between the fusion and postoperative MRI. The CT-MRI fusion images could be used to avoid the potential risks of MRI after DBS in patients with PD. Copyright © 2017. Published by Elsevier B.V.

Safety of the Transcranial Focal Electrical Stimulation via Tripolar Concentric Ring Electrodes for Hippocampal CA3 Subregion Neurons in Rats

PubMed Central

2017-01-01

Epilepsy is a neurological disorder that affects approximately one percent of the world population. Noninvasive electrical brain stimulation via tripolar concentric ring electrodes has been proposed as an alternative/complementary therapy for seizure control. Previous results suggest its efficacy attenuating acute seizures in penicillin, pilocarpine-induced status epilepticus, and pentylenetetrazole-induced rat seizure models and its safety for the rat scalp, cortical integrity, and memory formation. In this study, neuronal counting was used to assess possible tissue damage in rats (n = 36) due to the single dose or five doses (given every 24 hours) of stimulation on hippocampal CA3 subregion neurons 24 hours, one week, and one month after the last stimulation dose. Full factorial analysis of variance showed no statistically significant difference in the number of neurons between control and stimulation-treated animals (p = 0.71). Moreover, it showed no statistically significant differences due to the number of stimulation doses (p = 0.71) nor due to the delay after the last stimulation dose (p = 0.96). Obtained results suggest that stimulation at current parameters (50 mA, 200 μs, 300 Hz, biphasic, charge-balanced pulses for 2 minutes) does not induce neuronal damage in the hippocampal CA3 subregion of the brain. PMID:29065603

Safety of the Transcranial Focal Electrical Stimulation via Tripolar Concentric Ring Electrodes for Hippocampal CA3 Subregion Neurons in Rats.

PubMed

Mucio-Ramírez, Samuel; Makeyev, Oleksandr

2017-01-01

Epilepsy is a neurological disorder that affects approximately one percent of the world population. Noninvasive electrical brain stimulation via tripolar concentric ring electrodes has been proposed as an alternative/complementary therapy for seizure control. Previous results suggest its efficacy attenuating acute seizures in penicillin, pilocarpine-induced status epilepticus, and pentylenetetrazole-induced rat seizure models and its safety for the rat scalp, cortical integrity, and memory formation. In this study, neuronal counting was used to assess possible tissue damage in rats ( n = 36) due to the single dose or five doses (given every 24 hours) of stimulation on hippocampal CA3 subregion neurons 24 hours, one week, and one month after the last stimulation dose. Full factorial analysis of variance showed no statistically significant difference in the number of neurons between control and stimulation-treated animals ( p  = 0.71). Moreover, it showed no statistically significant differences due to the number of stimulation doses ( p  = 0.71) nor due to the delay after the last stimulation dose ( p  = 0.96). Obtained results suggest that stimulation at current parameters (50 mA, 200  μ s, 300 Hz, biphasic, charge-balanced pulses for 2 minutes) does not induce neuronal damage in the hippocampal CA3 subregion of the brain.

Anatomical origin of déjà vu and vivid 'memories' in human temporal lobe epilepsy.

PubMed

Bancaud, J; Brunet-Bourgin, F; Chauvel, P; Halgren, E

1994-02-01

Jackson (Brain 1898; 21: 580-90) observed that seizures arising in the medial temporal lobe may result in a 'dreamy state', consisting of vivid memory-like hallucinations, and/or the sense of having previously lived through exactly the same situation (déjà vu). Penfield demonstrated that the dreamy state can sometimes be evoked by electrical stimulation of the lateral temporal neocortex, especially the superior temporal gyrus. Halgren et al. (Brain 1978; 101: 83-117) showed that the dreamy state can be evoked by stimulation of the hippocampal formation and amygdala and Gloor (Brain 1990; 113: 1673-94) has suggested that it is evoked by lateral stimulation only when the resulting after-discharge spreads medially. In order to resolve the relative importance of these areas, we considered the mental phenomena observed in epileptic patients with electrodes stereotaxically implanted into different brain areas for seizure localization prior to surgical treatment. Sixteen patients, all with seizures involving the temporal lobe, experienced the dreamy state either as a result of spontaneous seizures (nine dreamy states in six patients), or due to electrical stimulation (43 in 14) or to chemical activation (five in three). Déjà vu and hallucinations of scenes were often evoked by different stimulations of the same electrode in the same patient. As Jackson had also observed, the dreamy state could occur alone but was often associated with epigastric phenomena and fear, and followed by loss of contact and oro-alimentary automatisms, and then by simple gestural automatisms, all characteristic of partial seizures beginning in the medial temporal lobe. Furthermore, as also emphasized by Jackson, the dreamy state was seldom associated with sensory illusions. Stimulation of either the neocortex (15 occurrences), anterior hippocampus (17) or amygdala (10) could evoke a dreamy state. However, since fewer hippocampal and amygdala leads were stimulated than temporal neocortical, the proportion of medial temporal electrodes where dreamy states could be evoked was much higher than in the neocortex. Most responsive lateral temporal sites were located in the superior temporal gyrus, rather than the middle temporal gyrus which was significantly less responsive. In 85% of dreamy states evoked by medial temporal lobe stimulation, the discharge spread to the temporal neocortex; and in 53% of dreamy states evoked by lateral temporal stimulation, the discharge spread medially. Considering all dreamy states, the amygdala was involved (as the stimulated structure, or as the site of ictal- or after-discharge) in 73% of cases, the anterior hippocampus in 83% and the temporal neocortex in 88%.(ABSTRACT TRUNCATED AT 400 WORDS)

Hypothalamic self-stimulation and stimulation escape in relation to feeding and mating.

PubMed

Hoebel, B G

1979-10-01

This review begins with James Olds' discovery that self-stimulation at various brain sites can be influenced by food intake or androgen treatment. It then describes our research designed to reveal the functional significance of self-stimulation. The evidence suggests that lateral hypothalamic self-stimulation is controlled by many of the same factors that control feeding. We believe this control is exerted by at least two neural mechanisms. One is the classical, medial hypothalamic satiety system. Another is an adrenergic system ascending from the midbrain to the lateral hypothalamus. Damage to either one can disinhibit self-stimulation and feeding, thus contributing to obesity. Some of our studies use rats with two electrodes, one that induces feeding and one that induces mating. There are two response levers in the test cage, one for self-stimulation and one for escape from automatic stimulation. With the feeding electrode, rats self-stimulated less and escaped more after a meal than before. The same shift occurred after an anorectic dose of insulin or the commercial appetite suppressant phenylpropanolamine. With the sex electrode the shift from reward to aversion occurred after ejaculation. The review ends with credit to James Olds for pioneering this line of research into the neuropsychology of reinforcement.

Preoperative DTI and probabilistic tractography in an amputee with deep brain stimulation for lower limb stump pain.

PubMed

Owen, S L F; Heath, J; Kringelbach, M L; Stein, J F; Aziz, T Z

2007-10-01

This study aimed to find out whether preoperative diffusion tensor imaging (DTI) and probabilistic tractography could help with surgical planning for deep brain stimulation in the periaqueductal/periventricular grey area (PAG/PVG) in a patient with lower leg stump pain. A preoperative DTI was obtained from the patient, who then received DBS surgery in the PAG/PVG area with good pain relief. The postoperative MRI scan showing electrode placement was used to calculate four seed areas to represent the contacts on the Medtronic 3387 electrode. Probabilistic tractography was then performed from the pre-operative DTI image. Tracts were seen to connect to many areas within the pain network from the four different contacts. These initial findings suggest that preoperative DTI scanning and probabilistic tractography may be able to assist surgical planning in the future.

Functional neuroanatomy of the insular lobe.

PubMed

Stephani, C; Fernandez-Baca Vaca, G; Maciunas, R; Koubeissi, M; Lüders, H O

2011-06-01

The insula is the fifth lobe of the brain and it is the least known. Hidden under the temporal, frontal and parietal opercula, as well as under dense arterial and venous vessels, its accessibility is particularly restricted. Functional data on this region in humans, therefore, are scarce and the existing evidence makes conclusions on its functional and somatotopic organization difficult. 5 patients with intractable epilepsy underwent an invasive presurgical evaluation with implantation of diagnostic invasive-depth electrodes, including insular electrodes that were inserted using a mesiocaudodorsal to laterorostroventral approach. Altogether 113 contacts were found to be in the insula and were stimulated with alternating currents during preoperative monitoring. Different viscerosensitive and somatosensory phenomena were elicited by stimulation of these electrodes. A relatively high density of electrode contacts enabled us to delineate several functionally distinct areas within the insula. We found somatosensory symptoms to be restricted to the posterior insula and a subgroup of warmth or painful sensations in the dorsal posterior insula. Viscerosensory symptoms were elicited by more anterior electrode contacts with a subgroup of gustatory symptoms occurring after stimulation of electrode contacts in the central part of the insula. The anterior insula did not show reproducible responses to stimulation. In line with previous studies, we found evidence for somato- and viscerosensory cortex in the insula. In addition, our results suggest that there is a predominantly posterior and central distribution of these functions in the insular lobe.

Noninvasive techniques for probing neurocircuitry and treating illness: vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS)

PubMed Central

George, Mark S; Aston-Jones, Gary

2010-01-01

Although the preceding chapters discuss much of the new knowledge of neurocircuitry of neuropsychiatric diseases, and an invasive approach to treatment, this chapter describes and reviews the noninvasive methods of testing circuit-based theories and treating neuropsychiatric diseases that do not involve implanting electrodes into the brain or on its surface. These techniques are transcranial magnetic stimulation, vagus nerve stimulation, and transcranial direct current stimulation. Two of these approaches have FDA approval as therapies. PMID:19693003

The nature of tremor circuits in parkinsonian and essential tremor

PubMed Central

Cagnan, Hayriye; Little, Simon; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Cheeran, Binith; Fitzgerald, James; Green, Alexander L.; Aziz, Tipu

2014-01-01

Tremor is a cardinal feature of Parkinson’s disease and essential tremor, the two most common movement disorders. Yet, the mechanisms underlying tremor generation remain largely unknown. We hypothesized that driving deep brain stimulation electrodes at a frequency closely matching the patient’s own tremor frequency should interact with neural activity responsible for tremor, and that the effect of stimulation on tremor should reveal the role of different deep brain stimulation targets in tremor generation. Moreover, tremor responses to stimulation might reveal pathophysiological differences between parkinsonian and essential tremor circuits. Accordingly, we stimulated 15 patients with Parkinson’s disease with either thalamic or subthalamic electrodes (13 male and two female patients, age: 50–77 years) and 10 patients with essential tremor with thalamic electrodes (nine male and one female patients, age: 34–74 years). Stimulation at near-to tremor frequency entrained tremor in all three patient groups (ventrolateral thalamic stimulation in Parkinson’s disease, P = 0.0078, subthalamic stimulation in Parkinson’s disease, P = 0.0312; ventrolateral thalamic stimulation in essential tremor, P = 0.0137; two-tailed paired Wilcoxon signed-rank tests). However, only ventrolateral thalamic stimulation in essential tremor modulated postural tremor amplitude according to the timing of stimulation pulses with respect to the tremor cycle (e.g. P = 0.0002 for tremor amplification, two-tailed Wilcoxon rank sum test). Parkinsonian rest and essential postural tremor severity (i.e. tremor amplitude) differed in their relative tolerance to spontaneous changes in tremor frequency when stimulation was not applied. Specifically, the amplitude of parkinsonian rest tremor remained unchanged despite spontaneous changes in tremor frequency, whereas that of essential postural tremor reduced when tremor frequency departed from median values. Based on these results we conclude that parkinsonian rest tremor is driven by a neural network, which includes the subthalamic nucleus and ventrolateral thalamus and has broad frequency-amplitude tolerance. We propose that it is this tolerance to changes in tremor frequency that dictates that parkinsonian rest tremor may be significantly entrained by low frequency stimulation without stimulation timing-dependent amplitude modulation. In contrast, the circuit influenced by low frequency thalamic stimulation in essential tremor has a narrower frequency-amplitude tolerance so that tremor entrainment through extrinsic driving is necessarily accompanied by amplitude modulation. Such differences in parkinsonian rest and essential tremor will be important in selecting future strategies for closed loop deep brain stimulation for tremor control. PMID:25200741

Potentiated antibodies to mu-opiate receptors: effect on integrative activity of the brain.

PubMed

Geiko, V V; Vorob'eva, T M; Berchenko, O G; Epstein, O I

2003-01-01

The effect of homeopathically potentiated antibodies to mu-receptors (10(-100) wt %) on integrative activity of rat brain was studied using the models of self-stimulation of the lateral hypothalamus and convulsions produced by electric current. Electric current was delivered through electrodes implanted into the ventromedial hypothalamus. Single treatment with potentiated antibodies to mu-receptors increased the rate of self-stimulation and decreased the threshold of convulsive seizures. Administration of these antibodies for 7 days led to further activation of the positive reinforcement system and decrease in seizure thresholds. Distilled water did not change the rate of self-stimulation and seizure threshold.

Systematic study of the effects of stimulus parameters and stimulus location on afterdischarges elicited by electrical stimulation in the rat.

PubMed

Shigeto, Hiroshi; Boongird, Atthaporn; Baker, Kenneth; Kellinghaus, Christoph; Najm, Imad; Lüders, Hans

2013-03-01

Electrical brain stimulation is used in a variety of clinical situations, including cortical mapping for epilepsy surgery, cortical stimulation therapy to terminate seizure activity in the cortex, and in deep brain stimulation therapy. However, the effects of stimulus parameters are not fully understood. In this study, we systematically tested the impact of various stimulation parameters on the generation of motor symptoms and afterdischarges (ADs). Focal electrical stimulation was delivered at subdural cortical, intracortical, and hippocampal sites in a rat model. The effects of stimulus parameter on the generation of motor symptoms and on the occurrence of ADs were examined. The effect of stimulus irregularity was tested using random or regular 50Hz stimulation through subdural electrodes. Hippocampal stimulation produced ADs at lower thresholds than neocortical stimulation. Hippocampal stimulation also produced significantly longer ADs. Both in hippocampal and cortical stimulation, when the total current was kept constant with changing pulse width, the threshold for motor symptom or AD was lowest between 50 and 100Hz and higher at both low and high frequencies. However, if the pulse width was fixed, the threshold did not increase above 100Hz and it apparently continued to decrease through 800Hz even if the difference did not reach statistical significance. There was no significant difference between random and regular stimulation. Overall, these results indicate that electrode location and several stimulus parameters including frequency, pulse width, and total electricity are important in electrical stimulation to produce motor symptoms and ADs. Copyright © 2012 Elsevier B.V. All rights reserved.

Electrophoretic deposition of ligand-free platinum nanoparticles on neural electrodes affects their impedance in vitro and in vivo with no negative effect on reactive gliosis.

PubMed

Angelov, Svilen D; Koenen, Sven; Jakobi, Jurij; Heissler, Hans E; Alam, Mesbah; Schwabe, Kerstin; Barcikowski, Stephan; Krauss, Joachim K

2016-01-12

Electrodes for neural stimulation and recording are used for the treatment of neurological disorders. Their features critically depend on impedance and interaction with brain tissue. The effect of surface modification on electrode impedance was examined in vitro and in vivo after intracranial implantation in rats. Electrodes coated by electrophoretic deposition with platinum nanoparticles (NP; <10 and 50 nm) as well as uncoated references were implanted into the rat's subthalamic nucleus. After postoperative recovery, rats were electrostimulated for 3 weeks. Impedance was measured before implantation, after recovery and then weekly during stimulation. Finally, local field potential was recorded and tissue-to-implant reaction was immunohistochemically studied. Coating with NP significantly increased electrode's impedance in vitro. Postoperatively, the impedance of all electrodes was temporarily further increased. This effect was lowest for the electrodes coated with particles <10 nm, which also showed the most stable impedance dynamics during stimulation for 3 weeks and the lowest total power of local field potential during neuronal activity recording. Histological analysis revealed that NP-coating did not affect glial reactions or neural cell-count. Coating with NP <10 nm may improve electrode's impedance stability without affecting biocompatibility. Increased impedance after NP-coating may improve neural recording due to better signal-to-noise ratio.

The evolution of endovascular electroencephalography: historical perspective and future applications.

PubMed

Sefcik, Roberta K; Opie, Nicholas L; John, Sam E; Kellner, Christopher P; Mocco, J; Oxley, Thomas J

2016-05-01

Current standard practice requires an invasive approach to the recording of electroencephalography (EEG) for epilepsy surgery, deep brain stimulation (DBS), and brain-machine interfaces (BMIs). The development of endovascular techniques offers a minimally invasive route to recording EEG from deep brain structures. This historical perspective aims to describe the technical progress in endovascular EEG by reviewing the first endovascular recordings made using a wire electrode, which was followed by the development of nanowire and catheter recordings and, finally, the most recent progress in stent-electrode recordings. The technical progress in device technology over time and the development of the ability to record chronic intravenous EEG from electrode arrays is described. Future applications for the use of endovascular EEG in the preoperative and operative management of epilepsy surgery are then discussed, followed by the possibility of the technique's future application in minimally invasive operative approaches to DBS and BMI.

Transcranial electric and magnetic stimulation: technique and paradigms.

PubMed

Paulus, Walter; Peterchev, Angel V; Ridding, Michael

2013-01-01

Transcranial electrical and magnetic stimulation techniques encompass a broad physical variety of stimuli, ranging from static magnetic fields or direct current stimulation to pulsed magnetic or alternating current stimulation with an almost infinite number of possible stimulus parameters. These techniques are continuously refined by new device developments, including coil or electrode design and flexible control of the stimulus waveforms. They allow us to influence brain function acutely and/or by inducing transient plastic after-effects in a range from minutes to days. Manipulation of stimulus parameters such as pulse shape, intensity, duration, and frequency, and location, size, and orientation of the electrodes or coils enables control of the immediate effects and after-effects. Physiological aspects such as stimulation at rest or during attention or activation may alter effects dramatically, as does neuropharmacological drug co-application. Non-linear relationships between stimulus parameters and physiological effects have to be taken into account. © 2013 Elsevier B.V. All rights reserved.

Technical Case Report of Deep Brain Stimulation: Is it Possible Single Electrode Reach to Both of Subthalamic Nucleus and Ventral Intermediate Nucleus in One Stage?

PubMed

Kaptan, Hülagu; Çakmur, Raif

2018-04-15

The primary target of this operation is Ventral Intermediate Nucleus (VIM); however VIM - Subthalamic Nucleus (STN) were tried to be reached with one electrode, adjusting the angle well, the coronal section; medial of VIM can partially reach the STN. Using the properties of the electrode; we believe we could act on a wide area. An analysis was performed on one patient who underwent VIM Deep Brain Stimulation (DBS) in 3 periods (pre - peri - post-operation). A 53 - year - old woman diagnosed with Parkinson's disease 8 years earlier including symptoms of severe tremor on the right than left underwent bilateral DBS VIM. Obtaining a satisfactory improvement of tremor, the patient did well, and postoperative complications were not observed. The patient was discharged from hospital on postoperative thirty day. It is certain that more research and experience are needed. However, we believe that the two targets can reach the same point and the second operations for another target can be avoided.We believe that this initiative is advantageous and promising regarding patient and cost.

Measurements and models of electric fields in the in vivo human brain during transcranial electric stimulation

PubMed Central

Huang, Yu; Liu, Anli A; Lafon, Belen; Friedman, Daniel; Dayan, Michael; Wang, Xiuyuan; Bikson, Marom; Doyle, Werner K; Devinsky, Orrin; Parra, Lucas C

2017-01-01

Transcranial electric stimulation aims to stimulate the brain by applying weak electrical currents at the scalp. However, the magnitude and spatial distribution of electric fields in the human brain are unknown. We measured electric potentials intracranially in ten epilepsy patients and estimated electric fields across the entire brain by leveraging calibrated current-flow models. When stimulating at 2 mA, cortical electric fields reach 0.8 V/m, the lower limit of effectiveness in animal studies. When individual whole-head anatomy is considered, the predicted electric field magnitudes correlate with the recorded values in cortical (r = 0.86) and depth (r = 0.88) electrodes. Accurate models require adjustment of tissue conductivity values reported in the literature, but accuracy is not improved when incorporating white matter anisotropy or different skull compartments. This is the first study to validate and calibrate current-flow models with in vivo intracranial recordings in humans, providing a solid foundation to target stimulation and interpret clinical trials. DOI: http://dx.doi.org/10.7554/eLife.18834.001 PMID:28169833

Postmortem volumetric analysis of the nucleus accumbens in male heroin addicts: implications for deep brain stimulation.

PubMed

Müller, Ulf J; Truebner, Kurt; Schiltz, Kolja; Kuhn, Jens; Mawrin, Christian; Dobrowolny, Henrik; Bernstein, Hans-Gert; Bogerts, Bernhard; Steiner, Johann

2015-12-01

Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is increasingly investigated in neuropsychiatric disorders. DBS requires computer-assisted 3D planning to implant the stimulation electrode precisely. Recently, there has been a debate about the true dimensions of NAc in healthy as well as in mentally ill individuals. Knowing its true dimensions in different neuropsychiatric disorders may improve even more precise targeting of NAc for therapeutic DBS. Volumes of NAc of heroin addicts (n = 14) and healthy controls (n = 12) were calculated by using morphometry of serial whole-brain sections. Total brain volume was larger in the heroin group (mean 1478.85 ± 62.34 vs. mean 1352.38 ± 103.24 cm(3)), as the heroin group was more than 10 years younger (p = 0.001). However, the mean volume of the NAc in heroin addicts was smaller than in controls (0.528 ± 0.166 vs. 0.623 ± 0.196 cm(3); p = 0.019). This group effect did not significantly differ between the hemispheres. When assessed separately, left-hemispheric NAc volume was 15 % lower (p = 0.020), while right-hemispheric NAc volume was 16 % lower (p = 0.047) in the heroin-addicted group compared to controls. Based on these diagnosis-related differences, we believe it is important to further analyze NAc volumes in different psychiatric disorders to further improve precise targeting and electrode placement.

Enhancing motor performance improvement by personalizing non-invasive cortical stimulation with concurrent functional near-infrared spectroscopy and multi-modal motor measurements

NASA Astrophysics Data System (ADS)

Khan, Bilal; Hodics, Timea; Hervey, Nathan; Kondraske, George; Stowe, Ann; Alexandrakis, George

2015-03-01

Transcranial direct current stimulation (tDCS) is a non-invasive cortical stimulation technique that can facilitate task specific plasticity that can improve motor performance. Current tDCS interventions uniformly apply a chosen electrode montage to a subject population without personalizing electrode placement for optimal motor gains. We propose a novel perturbation tDCS (ptDCS) paradigm for determining a personalized electrode montage in which tDCS intervention yields maximal motor performance improvements during stimulation. PtDCS was applied to ten healthy adults and five stroke patients with upper hemiparesis as they performed an isometric wrist flexion task with their non-dominant arm. Simultaneous recordings of torque applied to a stationary handle, muscle activity by electromyography (EMG), and cortical activity by functional near-infrared spectroscopy (fNIRS) during ptDCS helped interpret how cortical activity perturbations by any given electrode montage related to changes in muscle activity and task performance quantified by a Reaction Time (RT) X Error product. PtDCS enabled quantifying the effect on task performance of 20 different electrode pair montages placed over the sensorimotor cortex. Interestingly, the electrode montage maximizing performance in all healthy adults did not match any of the ones being explored in current literature as a means of improving the motor performance of stroke patients. Furthermore, the optimal montage was found to be different in each stroke patient and the resulting motor gains were very significant during stimulation. This study supports the notion that task-specific ptDCS optimization can lend itself to personalizing the rehabilitation of patients with brain injury.

The point spread function of the human head and its implications for transcranial current stimulation

NASA Astrophysics Data System (ADS)

Dmochowski, Jacek P.; Bikson, Marom; Parra, Lucas C.

2012-10-01

Rational development of transcranial current stimulation (tCS) requires solving the ‘forward problem’: the computation of the electric field distribution in the head resulting from the application of scalp currents. Derivation of forward models has represented a major effort in brain stimulation research, with model complexity ranging from spherical shells to individualized head models based on magnetic resonance imagery. Despite such effort, an easily accessible benchmark head model is greatly needed when individualized modeling is either undesired (to observe general population trends as opposed to individual differences) or unfeasible. Here, we derive a closed-form linear system which relates the applied current to the induced electric potential. It is shown that in the spherical harmonic (Fourier) domain, a simple scalar multiplication relates the current density on the scalp to the electric potential in the brain. Equivalently, the current density in the head follows as the spherical convolution between the scalp current distribution and the point spread function of the head, which we derive. Thus, if one knows the spherical harmonic representation of the scalp current (i.e. the electrode locations and current intensity to be employed), one can easily compute the resulting electric field at any point inside the head. Conversely, one may also readily determine the scalp current distribution required to generate an arbitrary electric field in the brain (the ‘backward problem’ in tCS). We demonstrate the simplicity and utility of the model with a series of characteristic curves which sweep across a variety of stimulation parameters: electrode size, depth of stimulation, head size and anode-cathode separation. Finally, theoretically optimal montages for targeting an infinitesimal point in the brain are shown.

Comparison of electric field strength and spatial distribution of electroconvulsive therapy and magnetic seizure therapy in a realistic human head model

PubMed Central

Lee, Won Hee; Lisanby, Sarah H.; Laine, Andrew F.; Peterchev, Angel V.

2017-01-01

Background This study examines the strength and spatial distribution of the electric field induced in the brain by electroconvulsive therapy (ECT) and magnetic seizure therapy (MST). Methods The electric field induced by standard (bilateral, right unilateral, and bifrontal) and experimental (focal electrically administered seizure therapy and frontomedial) ECT electrode configurations as well as a circular MST coil configuration was simulated in an anatomically realistic finite element model of the human head. Maps of the electric field strength relative to an estimated neural activation threshold were used to evaluate the stimulation strength and focality in specific brain regions of interest for these ECT and MST paradigms and various stimulus current amplitudes. Results The standard ECT configurations and current amplitude of 800–900 mA produced the strongest overall stimulation with median of 1.8–2.9 times neural activation threshold and more than 94% of the brain volume stimulated at suprathreshold level. All standard ECT electrode placements exposed the hippocampi to suprathreshold electric field, although there were differences across modalities with bilateral and right unilateral producing respectively the strongest and weakest hippocampal stimulation. MST stimulation is up to 9 times weaker compared to conventional ECT, resulting in direct activation of only 21% of the brain. Reducing the stimulus current amplitude can make ECT as focal as MST. Conclusions The relative differences in electric field strength may be a contributing factor for the cognitive sparing observed with right unilateral compared to bilateral ECT, and MST compared to right unilateral ECT. These simulations could help understand the mechanisms of seizure therapies and develop interventions with superior risk/benefit ratio. PMID:27318858

Electrode Position and Current Amplitude Modulate Impulsivity after Subthalamic Stimulation in Parkinsons Disease—A Computational Study

PubMed Central

Mandali, Alekhya; Chakravarthy, V. Srinivasa; Rajan, Roopa; Sarma, Sankara; Kishore, Asha

2016-01-01

Background: Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) is highly effective in alleviating motor symptoms of Parkinson's disease (PD) which are not optimally controlled by dopamine replacement therapy. Clinical studies and reports suggest that STN-DBS may result in increased impulsivity and de novo impulse control disorders (ICD). Objective/Hypothesis: We aimed to compare performance on a decision making task, the Iowa Gambling Task (IGT), in healthy conditions (HC), untreated and medically-treated PD conditions with and without STN stimulation. We hypothesized that the position of electrode and stimulation current modulate impulsivity after STN-DBS. Methods: We built a computational spiking network model of basal ganglia (BG) and compared the model's STN output with STN activity in PD. Reinforcement learning methodology was applied to simulate IGT performance under various conditions of dopaminergic and STN stimulation where IGT total and bin scores were compared among various conditions. Results: The computational model reproduced neural activity observed in normal and PD conditions. Untreated and medically-treated PD conditions had lower total IGT scores (higher impulsivity) compared to HC (P < 0.0001). The electrode position that happens to selectively stimulate the part of the STN corresponding to an advantageous panel on IGT resulted in de-selection of that panel and worsening of performance (P < 0.0001). Supratherapeutic stimulation amplitudes also worsened IGT performance (P < 0.001). Conclusion(s): In our computational model, STN stimulation led to impulsive decision making in IGT in PD condition. Electrode position and stimulation current influenced impulsivity which may explain the variable effects of STN-DBS reported in patients. PMID:27965590

Improved transcranial magnetic stimulation coil design with realistic head modeling

NASA Astrophysics Data System (ADS)

Crowther, Lawrence; Hadimani, Ravi; Jiles, David

2013-03-01

We are investigating Transcranial magnetic stimulation (TMS) as a noninvasive technique based on electromagnetic induction which causes stimulation of the neurons in the brain. TMS can be used as a pain-free alternative to conventional electroconvulsive therapy (ECT) which is still widely implemented for treatment of major depression. Development of improved TMS coils capable of stimulating subcortical regions could also allow TMS to replace invasive deep brain stimulation (DBS) which requires surgical implantation of electrodes in the brain. Our new designs allow new applications of the technique to be established for a variety of diagnostic and therapeutic applications of psychiatric disorders and neurological diseases. Calculation of the fields generated inside the head is vital for the use of this method for treatment. In prior work we have implemented a realistic head model, incorporating inhomogeneous tissue structures and electrical conductivities, allowing the site of neuronal activation to be accurately calculated. We will show how we utilize this model in the development of novel TMS coil designs to improve the depth of penetration and localization of stimulation produced by stimulator coils.

Simulation and assessment of cerebrovascular damage in deep brain stimulation using a stereotactic atlas of vasculature and structure derived from multiple 3- and 7-tesla scans.

PubMed

Nowinski, Wieslaw L; Chua, Beng Choon; Volkau, Ihar; Puspitasari, Fiftarina; Marchenko, Yevgen; Runge, Val M; Knopp, Michael V

2010-12-01

The most severe complication of deep brain stimulation (DBS) is intracranial hemorrhage. Detailed knowledge of the cerebrovasculature could reduce the rate of this disorder. Morphological scans typically acquired in stereotactic and functional neurosurgery (SFN) by using 1.5-T (or sometimes even 3-T) imaging units poorly depict the vasculature. Advanced angiographic imaging, including 3- and 7-T 3D time-of-flight and susceptibility weighted imaging as well as 320-slice CT angiography, depict the vessels in great detail. However, these acquisitions are not used in SFN clinical practice, and robust methods for their processing are not available yet. Therefore, the authors proposed the use of a detailed 3D stereotactic cerebrovascular atlas to assist in SFN planning and to potentially reduce DBS-induced hemorrhage. A very detailed 3D cerebrovascular atlas of arteries, veins, and dural sinuses was constructed from multiple 3- and 7-T scans. The atlas contained>900 vessels, each labeled with a name and diameter with the smallest having a 90-μm diameter. The cortical areas, ventricular system, and subcortical structures were fully segmented and labeled, including the main stereotactic target structures: subthalamic nucleus, ventral intermediate nucleus of the thalamus, and internal globus pallidus. The authors also developed a computer simulator with the embedded atlas that was able to compute the effective electrode trajectory by minimizing penetration of the cerebrovascular system and vital brain structures by a DBS electrode. The simulator provides the neurosurgeon with functions for atlas manipulation, target selection, trajectory planning and editing, 3D display and manipulation, and electrode-brain penetration calculation. This simulation demonstrated that a DBS electrode inserted in the middle frontal gyrus may intersect several arteries and veins including 1) the anteromedial frontal artery of the anterior cerebral artery as well as the prefrontal artery and the precentral sulcus artery of the middle cerebral artery (range of diameters 0.4-0.6 mm); and 2) the prefrontal, anterior caudate, and medullary veins (range of diameters 0.1-2.3 mm). This work also shows that field strength and pulse sequence have a substantial impact on vessel depiction. The numbers of 3D vascular segments are 215, 363, and 907 for 1.5-, 3-, and 7-T scans, respectively. Inserting devices into the brain during microrecording and stimulation may cause microbleeds not discernible on standard scans. A small change in the location of the DBS electrode can result in a major change for the patient. The described simulation increases the neurosurgeon's awareness of this phenomenon. The simulator enables the neurosurgeon to analyze the spatial relationships between the track and the cerebrovasculature, ventricles, subcortical structures, and cortical areas, which allows the DBS electrode to be placed more effectively, and thus potentially reducing the invasiveness of the stimulation procedure for the patient.

Contributions to singing ability by the posterior portion of the superior temporal gyrus of the non-language-dominant hemisphere: First evidence from subdural cortical stimulation, Wada testing, and fMRI

PubMed Central

Suarez, Ralph O.; Golby, Alexandra; Whalen, Stephen; Sato, Susumu; Theodore, William H.; Kufta, Conrad V.; Devinsky, Orrin; Balish, Marshall; Bromfield, Edward B.

2009-01-01

INTRODUCTION Although the substrates that mediate singing abilities in the human brain are not well understood, invasive brain mapping techniques used for clinical decision making such as intracranial electrocortical testing and Wada testing offer a rare opportunity to examine music-related function in a select group of subjects, affording exceptional spatial and temporal specificity. METHODS We studied eight patients with medically refractory epilepsy undergoing indwelling subdural electrode seizure focus localization. All patients underwent Wada testing for language lateralization. Functional assessment of language and music tasks was done by electrode grid cortical stimulation. One patient was also tested non-invasively with functional MRI. Functional organization of singing ability compared to language ability was determined based on four regions-ofinterest: left and right inferior frontal gyrus (IFG), and left and right posterior superior temporal gyrus (pSTG). RESULTS In some subjects, electrical stimulation of dominant pSTG can interfere with speech and not singing, whereas stimulation of non-dominant pSTG area can interfere with singing and not speech. Stimulation of the dominant IFG tends to interfere with both musical and language expression, while non-dominant IFG stimulation was often observed to cause no interference with either task; and finally, that stimulation of areas adjacent to but not within non-dominant pSTG typically does not affect either ability. FMRI mappings of one subject revealed similar music/language dissociation with respect to activation asymmetry within the regions-of-interest. CONCLUSION Despite inherent limitations with respect to strictly research objectives, invasive clinical techniques offer a rare opportunity to probe musical and language cognitive processes of the brain in a select group of patients. PMID:19570530

A cognitive neuroprosthetic that uses cortical stimulation for somatosensory feedback

PubMed Central

Klaes, Christian; Shi, Ying; Kellis, Spencer; Minxha, Juri; Revechkis, Boris; Andersen, Richard A.

2015-01-01

Present day cortical brain machine interfaces (BMI) have made impressive advances using decoded brain signals to control extracorporeal devices. Although BMIs are used in a closed-loop fashion, sensory feedback typically is visual only. However medical case studies have shown that the loss of somesthesis in a limb greatly reduces the agility of the limb even when visual feedback is available (for review see Robles-De-La-Torre, 2006). To overcome this limitation, this study tested a closed-loop BMI that utilizes intracortical microstimulation (ICMS) to provide ‘tactile’ sensation to a non-human primate (NHP). Using stimulation electrodes in Brodmann area 1 of somatosensory cortex (BA1) and recording electrodes in the anterior intraparietal area (AIP), the parietal reach region (PRR) and dorsal area 5 (area 5d), it was found that this form of feedback can be used in BMI tasks. PMID:25242377

Effect of micro lesions of the basal ganglia on ballistic movements in patients with deep brain stimulation.

PubMed

Singh, Arun; Mehrkens, Jan H; Bötzel, Kai

2012-03-15

Bradykinesia and hypokinesia are the prominent symptoms of substantia nigra degeneration in Parkinson's disease (PD). In segmental dystonia, movements of not affected limbs are not impaired. Here we studied the impact of the mere implantation of stimulation electrodes on the performance of fast movements in these two groups. We investigated 9 PD patients with subthalamic electrodes and 9 patients with segmental dystonia with electrodes in the globus pallidus internum. Patients were studied on the first postoperative day without electrical stimulation of the electrodes. Subjects had to perform boxing movements with either touching the target or stopping the fist in front of the target. PD subjects performed significantly faster movements in the touch-task only as compared to dystonic patients. No difference was seen in the stopping task. In conclusion, our findings suggest that a small subthalamic lesion in individuals with PD specifically reverses bradykinesia during simple ballistic movements (touch) but not during complex ones requiring more pre-programming (no-touch paradigm). Copyright © 2011 Elsevier B.V. All rights reserved.

Integration of sparse electrophysiological measurements with preoperative MRI using 3D surface estimation in deep brain stimulation surgery

NASA Astrophysics Data System (ADS)

Husch, Andreas; Gemmar, Peter; Thunberg, Johan; Hertel, Frank

2017-03-01

Intraoperative microelectrode recordings (MER) have been used for several decades to guide neurosurgeons during the implantation of Deep Brain Stimulation (DBS) electrodes, especially when targeting the subthalamic nucleus (STN) to suppress the symptoms of Parkinson's Disease. The standard approach is to use an array of up to five MER electrodes in a fixed configuration. Interpretation of the recorded signals yields a spatially very sparse set of information about the morphology of the respective brain structures in the targeted area. However, no aid is currently available for surgeons to intraoperatively integrate this information with other data available on the patient's individual morphology (e.g. MR imaging data used for surgical planning). This integration might allow surgeons to better determine the most probable position of the electrodes within the target structure during surgery. This paper suggests a method for reconstructing a surface patch from the sparse MER dataset utilizing additional a priori knowledge about the geometrical configuration of the measurement electrodes. The conventional representation of MER measurements as intervals of target region/non-target region is therefore transformed into an equivalent boundary set representation, allowing ecient point-based calculations. Subsequently, the problem is to integrate the resulting patch with a preoperative model of the target structure, which can be formulated as registration problem minimizing a distance measure between the two surfaces. When restricting this registration procedure to translations, which is reasonable given certain geometric considerations, the problem can be solved globally by employing an exhaustive search with arbitrary precision in polynomial time. The proposed method is demonstrated using bilateral STN/Substantia Nigra segmentation data from preoperative MRIs of 17 Patients with simulated MER electrode placement. When using simulated data of heavily perturbed electrodes and subsequent MER measurements, our optimization resulted in an improvement of the electrode position within 1 mm of the ground truth in 80.29% of the cases.

Carbon Nanofiber Electrode Array for Neurochemical Monitoring

NASA Technical Reports Server (NTRS)

Koehne, Jessica E.

2017-01-01

A sensor platform based on vertically aligned carbon nanofibers (CNFs) has been developed. Their inherent nanometer scale, high conductivity, wide potential window, good biocompatibility and well-defined surface chemistry make them ideal candidates as biosensor electrodes. Here, we report using vertically aligned CNF as neurotransmitter recording electrodes for application in a smart deep brain stimulation (DBS) device. Our approach combines a multiplexed CNF electrode chip, developed at NASA Ames Research Center, with the Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS) system, developed at the Mayo Clinic. Preliminary results indicate that the CNF nanoelectrode arrays are easily integrated with WINCS for neurotransmitter detection in a multiplexed array format. In the future, combining CNF based stimulating and recording electrodes with WINCS may lay the foundation for an implantable smart therapeutic system that utilizes neurochemical feedback control while likely resulting in increased DBS application in various neuropsychiatric disorders. In total, our goal is to take advantage of the nanostructure of CNF arrays for biosensing studies requiring ultrahigh sensitivity, high-degree of miniaturization, and selective biofunctionalization.

Hyperhidrosis associated with subthalamic deep brain stimulation in Parkinson's disease: Insights into central autonomic functional anatomy.

PubMed

Ramirez-Zamora, Adolfo; Smith, Heather; Youn, Youngwon; Durphy, Jennifer; Shin, Damian S; Pilitsis, Julie G

2016-07-15

There is limited evidence regarding the precise location and connections of thermoregulatory centers in humans. We present two patients managed with subthalamic nucleus (STN) Deep Brain Stimulation (DBS) for motor fluctuations in PD that developed reproducible hyperhidrosis with high frequency DBS. To describe the clinical features and analyze the location of the electrodes leading to autonomic activation in both patients. We retrospectively assessed the anatomical localization, electrode programming settings and effects of unilateral STN DBS leading to hyperhidrosis. Unilateral stimulation of anterior and medially located contacts within the STN and zona incerta (Zi) caused bilateral, consistent, reproducible, and reversible sweating in our patients. Adequate control of motor symptoms without autonomic side effects was accomplished with alternative programming settings. Stimulation of the medial Zi and medial and anterior STN causes hyperhidrosis in a pattern similar to that described in primates and rats. We speculate that central autonomic fibers originating in the lateral hypothalamic area project laterally to the ventral/medial Zi and then to brainstem nuclei following an medial and posterior trajectory in relationship to STN. Copyright © 2016 Elsevier B.V. All rights reserved.

Adaptive deep brain stimulation in advanced Parkinson disease.

PubMed

Little, Simon; Pogosyan, Alex; Neal, Spencer; Zavala, Baltazar; Zrinzo, Ludvic; Hariz, Marwan; Foltynie, Thomas; Limousin, Patricia; Ashkan, Keyoumars; FitzGerald, James; Green, Alexander L; Aziz, Tipu Z; Brown, Peter

2013-09-01

Brain-computer interfaces (BCIs) could potentially be used to interact with pathological brain signals to intervene and ameliorate their effects in disease states. Here, we provide proof-of-principle of this approach by using a BCI to interpret pathological brain activity in patients with advanced Parkinson disease (PD) and to use this feedback to control when therapeutic deep brain stimulation (DBS) is delivered. Our goal was to demonstrate that by personalizing and optimizing stimulation in real time, we could improve on both the efficacy and efficiency of conventional continuous DBS. We tested BCI-controlled adaptive DBS (aDBS) of the subthalamic nucleus in 8 PD patients. Feedback was provided by processing of the local field potentials recorded directly from the stimulation electrodes. The results were compared to no stimulation, conventional continuous stimulation (cDBS), and random intermittent stimulation. Both unblinded and blinded clinical assessments of motor effect were performed using the Unified Parkinson's Disease Rating Scale. Motor scores improved by 66% (unblinded) and 50% (blinded) during aDBS, which were 29% (p = 0.03) and 27% (p = 0.005) better than cDBS, respectively. These improvements were achieved with a 56% reduction in stimulation time compared to cDBS, and a corresponding reduction in energy requirements (p < 0.001). aDBS was also more effective than no stimulation and random intermittent stimulation. BCI-controlled DBS is tractable and can be more efficient and efficacious than conventional continuous neuromodulation for PD. Copyright © 2013 American Neurological Association.

Non-invasive brain stimulation to investigate language production in healthy speakers: A meta-analysis.

PubMed

Klaus, Jana; Schutter, Dennis J L G

2018-06-01

Non-invasive brain stimulation (NIBS) has become a common method to study the interrelations between the brain and language functioning. This meta-analysis examined the efficacy of transcranial magnetic stimulation (TMS) and direct current stimulation (tDCS) in the study of language production in healthy volunteers. Forty-five effect sizes from 30 studies which investigated the effects of NIBS on picture naming or verbal fluency in healthy participants were meta-analysed. Further sub-analyses investigated potential influences of stimulation type, control, target site, task, online vs. offline application, and current density of the target electrode. Random effects modelling showed a small, but reliable effect of NIBS on language production. Subsequent analyses indicated larger weighted mean effect sizes for TMS as compared to tDCS studies. No statistical differences for the other sub-analyses were observed. We conclude that NIBS is a useful method for neuroscientific studies on language production in healthy volunteers. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Intraoperative neurophysiological responses in epileptic patients submitted to hippocampal and thalamic deep brain stimulation.

PubMed

Cukiert, Arthur; Cukiert, Cristine Mella; Argentoni-Baldochi, Meire; Baise, Carla; Forster, Cássio Roberto; Mello, Valeria Antakli; Burattini, José Augusto; Lima, Alessandra Moura

2011-12-01

Deep brain stimulation (DBS) has been used in an increasing frequency for treatment of refractory epilepsy. Acute deep brain macrostimulation intraoperative findings were sparsely published in the literature. We report on our intraoperative macrostimulation findings during thalamic and hippocampal DBS implantation. Eighteen patients were studied. All patients underwent routine pre-operative evaluation that included clinical history, neurological examination, interictal and ictal EEG, high resolution 1.5T MRI and neuropsychological testing. Six patients with temporal lobe epilepsy were submitted to hippocampal DBS (Hip-DBS); 6 patients with focal epilepsy were submitted to anterior thalamic nucleus DBS (AN-DBS) and 6 patients with generalized epilepsy were submitted to centro-median thalamic nucleus DBS (CM-DBS). Age ranged from 9 to 40 years (11 males). All patients were submitted to bilateral quadripolar DBS electrode implantation in a single procedure, under general anesthesia, and intraoperative scalp EEG monitoring. Final electrode's position was checked postoperatively using volumetric CT scanning. Bipolar stimulation using the more proximal and distal electrodes was performed. Final standard stimulation parameters were 6Hz, 4V, 300μs (low frequency range: LF) or 130Hz, 4V, 300μs (high frequency range: HF). Bilateral recruiting response (RR) was obtained after unilateral stimulation in all patients submitted to AN and CM-DBS using LF stimulation. RR was widespread but prevailed over the fronto-temporal region bilaterally, and over the stimulated hemisphere. HF stimulation led to background slowing and a DC shift. The mean voltage for the appearance of RR was 4V (CM) and 3V (AN). CM and AN-DBS did not alter inter-ictal spiking frequency or morphology. RR obtained after LF Hip-DBS was restricted to the stimulated temporal lobe and no contralateral activation was noted. HF stimulation yielded no visually recognizable EEG modification. Mean intensity for initial appearance of RR was 3V. In 5 of the 6 patients submitted to Hip-DBS, an increase in inter-ictal spiking was noted unilaterally immediately after electrode insertion. Intraoperative LF stimulation did not modify temporal lobe spiking; on the other hand, HF was effective in abolishing inter-ictal spiking in 4 of the 6 patients studied. There was no immediate morbidity or mortality in this series. Macrostimulation might be used to confirm that the hardware was working properly. There was no typical RR derived from each studied thalamic nuclei after LF stimulation. On the other hand, absence of such RRs was highly suggestive of hardware malfunction or inadequate targeting. Thalamic-DBS (Th-DBS) RR was always bilateral after unilateral stimulation, although they somehow prevailed over the stimulated hemisphere. Contrary to Th-DBS, Hip-DBS gave rise to localized RR over the ipsolateral temporal neocortex, and absence of this response might very likely be related to inadequate targeting or hardware failure. Increased spiking was seen over temporal neocortex during hippocampal electrode insertion; this might point to the more epileptogenic hippocampal region in each individual patient. We did not notice any intraoperative response difference among patients with temporal lobe epilepsy with or without MTS. The relationship between these intraoperative findings and seizure outcome is not yet clear and should be further evaluated. 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Single electrode micro-stimulation of rat auditory cortex: an evaluation of behavioral performance.

PubMed

Rousche, Patrick J; Otto, Kevin J; Reilly, Mark P; Kipke, Daryl R

2003-05-01

A combination of electrophysiological mapping, behavioral analysis and cortical micro-stimulation was used to explore the interrelation between the auditory cortex and behavior in the adult rat. Auditory discriminations were evaluated in eight rats trained to discriminate the presence or absence of a 75 dB pure tone stimulus. A probe trial technique was used to obtain intensity generalization gradients that described response probabilities to mid-level tones between 0 and 75 dB. The same rats were then chronically implanted in the auditory cortex with a 16 or 32 channel tungsten microwire electrode array. Implanted animals were then trained to discriminate the presence of single electrode micro-stimulation of magnitude 90 microA (22.5 nC/phase). Intensity generalization gradients were created to obtain the response probabilities to mid-level current magnitudes ranging from 0 to 90 microA on 36 different electrodes in six of the eight rats. The 50% point (the current level resulting in 50% detections) varied from 16.7 to 69.2 microA, with an overall mean of 42.4 (+/-8.1) microA across all single electrodes. Cortical micro-stimulation induced sensory-evoked behavior with similar characteristics as normal auditory stimuli. The results highlight the importance of the auditory cortex in a discrimination task and suggest that micro-stimulation of the auditory cortex might be an effective means for a graded information transfer of auditory information directly to the brain as part of a cortical auditory prosthesis.

Image-guided preoperative prediction of pyramidal tract side effect in deep brain stimulation

NASA Astrophysics Data System (ADS)

Baumgarten, C.; Zhao, Y.; Sauleau, P.; Malrain, C.; Jannin, P.; Haegelen, C.

2016-03-01

Deep brain stimulation of the medial globus pallidus is a surgical procedure for treating patients suffering from Parkinson's disease. Its therapeutic effect may be limited by the presence of pyramidal tract side effect (PTSE). PTSE is a contraction time-locked to the stimulation when the current spreading reaches the motor fibers of the pyramidal tract within the internal capsule. The lack of side-effect predictive model leads the neurologist to secure an optimal electrode placement by iterating clinical testing on an awake patient during the surgical procedure. The objective of the study was to propose a preoperative predictive model of PTSE. A machine learning based method called PyMAN (for Pyramidal tract side effect Model based on Artificial Neural network) that accounted for the current of the stimulation, the 3D electrode coordinates and the angle of the trajectory, was designed to predict the occurrence of PTSE. Ten patients implanted in the medial globus pallidus have been tested by a clinician to create a labeled dataset of the stimulation parameters that trigger PTSE. The kappa index value between the data predicted by PyMAN and the labeled data was .78. Further evaluation studies are desirable to confirm whether PyMAN could be a reliable tool for assisting the surgeon to prevent PTSE during the preoperative planning.

Programming for Stimulation-Induced Transient Nonmotor Psychiatric Symptoms after Bilateral Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease

PubMed Central

Wu, Xi; Qiu, Yiqing; Simfukwe, Keith; Wang, Jiali; Chen, Jianchun

2017-01-01

Background Stimulation-induced transient nonmotor psychiatric symptoms (STPSs) are side effects following bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) patients. We designed algorithms which (1) determine the electrode contacts that induce STPSs and (2) provide a programming protocol to eliminate STPS and maintain the optimal motor functions. Our objective is to test the effectiveness of these algorithms. Materials and Methods 454 PD patients who underwent programming sessions after STN-DBS implantations were retrospectively analyzed. Only STPS patients were enrolled. In these patients, the contacts inducing STPS were found and the programming protocol algorithms used. Results Eleven patients were diagnosed with STPS. Of these patients, two had four episodes of crying, and two had four episodes of mirthful laughter. In one patient, two episodes of abnormal sense of spatial orientation were observed. Hallucination episodes were observed twice in one patient, while five patients recorded eight episodes of hypomania. There were no statistical differences between the UPDRS-III under the final stimulation parameter (without STPS) and previous optimum UPDRS-III under the STPSs (p = 1.000). Conclusion The flow diagram used for determining electrode contacts that induce STPS and the programming protocol employed in the treatment of these symptoms are effective. PMID:28894620

Improvements in Memory after Medial Septum Stimulation Are Associated with Changes in Hippocampal Cholinergic Activity and Neurogenesis

PubMed Central

Jeong, Da Un; Lee, Ji Eun; Lee, Sung Eun; Chang, Won Seok; Kim, Sung June; Chang, Jin Woo

2014-01-01

Deep brain stimulation (DBS) has been found to have therapeutic effects in patients with dementia, but DBS mechanisms remain elusive. To provide evidence for the effectiveness of DBS as a treatment for dementia, we performed DBS in a rat model of dementia with intracerebroventricular administration of 192 IgG-saporins. We utilized four groups of rats, group 1, unlesioned control; group 2, cholinergic lesion; group 3, cholinergic lesion plus medial septum (MS) electrode implantation (sham stimulation); group 4, cholinergic lesions plus MS electrode implantation and stimulation. During the probe test in the water maze, performance of the lesion group decreased for measures of time spent and the number of swim crossings over the previous platform location. Interestingly, the stimulation group showed an equivalent performance to the normal group on all measures. And these are partially reversed by the electrode implantation. Acetylcholinesterase activity in the hippocampus was decreased in lesion and implantation groups, whereas activity in the stimulation group was not different from the normal group. Hippocampal neurogenesis was increased in the stimulation group. Our results revealed that DBS of MS restores spatial memory after damage to cholinergic neurons. This effect is associated with an increase in hippocampal cholinergic activity and neurogenesis. PMID:25101288

Contribution of transcranial magnetic stimulation to assessment of brain connectivity and networks.

PubMed

Hallett, Mark; Di Iorio, Riccardo; Rossini, Paolo Maria; Park, Jung E; Chen, Robert; Celnik, Pablo; Strafella, Antonio P; Matsumoto, Hideyuki; Ugawa, Yoshikazu

2017-11-01

The goal of this review is to show how transcranial magnetic stimulation (TMS) techniques can make a contribution to the study of brain networks. Brain networks are fundamental in understanding how the brain operates. Effects on remote areas can be directly observed or identified after a period of stimulation, and each section of this review will discuss one method. EEG analyzed following TMS is called TMS-evoked potentials (TEPs). A conditioning TMS can influence the effect of a test TMS given over the motor cortex. A disynaptic connection can be tested also by assessing the effect of a pre-conditioning stimulus on the conditioning-test pair. Basal ganglia-cortical relationships can be assessed using electrodes placed in the process of deep brain stimulation therapy. Cerebellar-cortical relationships can be determined using TMS over the cerebellum. Remote effects of TMS on the brain can be found as well using neuroimaging, including both positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). The methods complement each other since they give different views of brain networks, and it is often valuable to use more than one technique to achieve converging evidence. The final product of this type of work is to show how information is processed and transmitted in the brain. Published by Elsevier B.V.

Radiofrequency Lesions through Deep Brain Stimulation Electrodes in Movement Disorders: Case Report and Review of the Literature.

PubMed

Pérez-Suárez, Javier; Torres Díaz, Cristina V; López Manzanares, Lydia; Navas García, Marta; Pastor, Jesús; Barrio Fernández, Patricia; G de Sola, Rafael

2017-01-01

Although there are few reports of radiofrequency lesions performed through deep brain stimulation (DBS) electrodes in patients with movement disorders, experience with this method is scarce. We present 2 patients who had been previously treated with DBS of subthalamic nuclei (STN) and the ventral intermediate (VIM) nucleus of the thalamus for Parkinson's disease and essential tremor, respectively, and underwent a radiofrequency lesion through their DBS electrodes after developing a hardware infection. The authors conduct a review of the literature regarding this method. Both patients had a good clinical outcome after 20 and 8 months, respectively, as assessed by a reduction in Fahn-Tolosa-Marin Scale and Unified Parkinson's Disease Rating Scale scores. The second patient underwent a second DBS system implantation surgery after his radiofrequency treatment to optimize his management, achieving optimal clinical control with lower current and drug requirements than before the radiofrequency intervention. No adverse effects were observed. Radiofrequency lesions through DBS electrodes allow the creation of small and localized lesions. Its effectiveness and low-risk profile, in addition to its low cost, make this procedure suitable and a possible alternative in the therapeutic repertoire for the surgical treatment of movement disorders. © 2017 S. Karger AG, Basel.

Auditory steady-state responses in cochlear implant users: Effect of modulation frequency and stimulation artifacts.

PubMed

Gransier, Robin; Deprez, Hanne; Hofmann, Michael; Moonen, Marc; van Wieringen, Astrid; Wouters, Jan

2016-05-01

Previous studies have shown that objective measures based on stimulation with low-rate pulse trains fail to predict the threshold levels of cochlear implant (CI) users for high-rate pulse trains, as used in clinical devices. Electrically evoked auditory steady-state responses (EASSRs) can be elicited by modulated high-rate pulse trains, and can potentially be used to objectively determine threshold levels of CI users. The responsiveness of the auditory pathway of profoundly hearing-impaired CI users to modulation frequencies is, however, not known. In the present study we investigated the responsiveness of the auditory pathway of CI users to a monopolar 500 pulses per second (pps) pulse train modulated between 1 and 100 Hz. EASSRs to forty-three modulation frequencies, elicited at the subject's maximum comfort level, were recorded by means of electroencephalography. Stimulation artifacts were removed by a linear interpolation between a pre- and post-stimulus sample (i.e., blanking). The phase delay across modulation frequencies was used to differentiate between the neural response and a possible residual stimulation artifact after blanking. Stimulation artifacts were longer than the inter-pulse interval of the 500pps pulse train for recording electrodes ipsilateral to the CI. As a result the stimulation artifacts could not be removed by artifact removal on the bases of linear interpolation for recording electrodes ipsilateral to the CI. However, artifact-free responses could be obtained in all subjects from recording electrodes contralateral to the CI, when subject specific reference electrodes (Cz or Fpz) were used. EASSRs to modulation frequencies within the 30-50 Hz range resulted in significant responses in all subjects. Only a small number of significant responses could be obtained, during a measurement period of 5 min, that originate from the brain stem (i.e., modulation frequencies in the 80-100 Hz range). This reduced synchronized activity of brain stem responses in long-term severely-hearing impaired CI users could be an attribute of processes associated with long-term hearing impairment and/or electrical stimulation. Copyright © 2016 Elsevier B.V. All rights reserved.

The impact of multichannel microelectrode recording (MER) in deep brain stimulation of the basal ganglia.

PubMed

Kinfe, Thomas M; Vesper, Jan

2013-01-01

Deep brain stimulation (DBS) of the basal ganglia (Ncl. subthalamicus, Ncl. ventralis intermedius thalami, globus pallidus internus) has become an evidence-based and well-established treatment option in otherwise refractory movement disorders. The Ncl. subthalamicus (STN) is the target of choice in Parkinson's disease.However, a considerable discussion is currently ongoing with regard to the necessity for micro-electrode recording (MER) in DBS surgery.The present review provides an overview on deep brain stimulation and (MER) of the STN in patients with Parkinson's disease. Detailed description is given concerning the multichannel MER systems nowadays available for DBS of the basal ganglia, especially of the STN, as a useful tool for target refinement. Furthermore, an overview is given of the historical aspects, spatial mapping of the STN by MER, and its impact for accuracy and precision in current functional stereotactic neurosurgery.The pros concerning target refinement by MER means on the one hand, and cons including increased bleeding risk, increased operation time, local or general anesthesia, and single versus multichannel microelectrode recording are discussed in detail. Finally, the authors favor the use of MER with intraoperative testing combined with imaging to achieve a more precise electrode placement, aiming to ameliorate clinical outcome in therapy-resistant movement disorders.

Deep brain stimulation as a functional scalpel.

PubMed

Broggi, G; Franzini, A; Tringali, G; Ferroli, P; Marras, C; Romito, L; Maccagnano, E

2006-01-01

Since 1995, at the Istituto Nazionale Neurologico "Carlo Besta" in Milan (INNCB,) 401 deep brain electrodes were implanted to treat several drug-resistant neurological syndromes (Fig. 1). More than 200 patients are still available for follow-up and therapeutical considerations. In this paper our experience is reviewed and pioneered fields are highlighted. The reported series of patients extends the use of deep brain stimulation beyond the field of Parkinson's disease to new fields such as cluster headache, disruptive behaviour, SUNCt, epilepsy and tardive dystonia. The low complication rate, the reversibility of the procedure and the available image guided surgery tools will further increase the therapeutic applications of DBS. New therapeutical applications are expected for this functional scalpel.

A Programmable High-Voltage Compliance Neural Stimulator for Deep Brain Stimulation in Vivo

PubMed Central

Gong, Cihun-Siyong Alex; Lai, Hsin-Yi; Huang, Sy-Han; Lo, Yu-Chun; Lee, Nicole; Chen, Pin-Yuan; Tu, Po-Hsun; Yang, Chia-Yen; Lin, James Chang-Chieh; Chen, You-Yin

2015-01-01

Deep brain stimulation (DBS) is one of the most effective therapies for movement and other disorders. The DBS neurosurgical procedure involves the implantation of a DBS device and a battery-operated neurotransmitter, which delivers electrical impulses to treatment targets through implanted electrodes. The DBS modulates the neuronal activities in the brain nucleus for improving physiological responses as long as an electric discharge above the stimulation threshold can be achieved. In an effort to improve the performance of an implanted DBS device, the device size, implementation cost, and power efficiency are among the most important DBS device design aspects. This study aims to present preliminary research results of an efficient stimulator, with emphasis on conversion efficiency. The prototype stimulator features high-voltage compliance, implemented with only a standard semiconductor process, without the use of extra masks in the foundry through our proposed circuit structure. The results of animal experiments, including evaluation of evoked responses induced by thalamic electrical stimuli with our fabricated chip, were shown to demonstrate the proof of concept of our design. PMID:26029954

MRI-Guided Regional Personalized Electrical Stimulation in Multisession and Home Treatments

PubMed Central

Cancelli, Andrea; Cottone, Carlo; Giordani, Alessandro; Asta, Giampiero; Lupoi, Domenico; Pizzella, Vittorio; Tecchio, Franca

2018-01-01

The shape and position of the electrodes is a key factor for the efficacy of transcranial electrical stimulations (tES). We have recently introduced the Regional Personalized Electrode (RePE), a tES electrode fitting the personal cortical folding, that has been able to differentiate the stimulation of close by regions, in particular the primary sensory (S1) and motor (M1) cortices, and to personalize tES onto such an extended cortical district. However, neuronavigation on individual brain was compulsory for the correct montage. Here, we aimed at developing and testing a neuronavigation-free procedure for easy and quick positioning RePE, enabling multisession RePE-tES at home. We used off-line individual MRI to shape RePE via an ad-hoc computerized procedure, while an ad-hoc developed Adjustable Helmet Frame (AHF) was used to properly position it in multisession treatments, even at home. We used neuronavigation to test the RePE shape and position obtained by the new computerized procedure and the re-positioning obtained via the AHF. Using Finite Element Method (FEM) model, we also estimated the intra-cerebral current distribution induced by transcranial direct current stimulation (tDCS) comparing RePE vs. non-RePE with fixed reference. Additionally, we tested, using FEM, various shapes, and positions of the reference electrode taking into account possible small displacements of RePE, to test feasibility of RePE-tES sessions at home. The new RePE neuronavigation-free positioning relies on brain MRI space distances, and produced a mean displacement of 3.5 ± 0.8 mm, and the re-positioning of 4.8 ± 1.1 mm. Higher electric field in S1 than in M1 was best obtained with the occipital reference electrode, a montage that proved to feature low sensitivity to typical RePE millimetric displacements. Additionally, a new tES accessory was developed to enable repositioning the electrodes over the scalp also at home, with a precision which is acceptable according to the modeling-estimated intracerebral currents. Altogether, we provide here a procedure to simplify and make easily applicable RePE-tDCS, which enables efficacious personalized treatments. PMID:29867308

Microfluidic Actuation of Carbon Nanotube Fibers for Neural Recordings

NASA Astrophysics Data System (ADS)

Vercosa, Daniel G.

Implantable devices to record and stimulate neural circuits have led to breakthroughs in neuroscience; however, technologies capable of electrical recording at the cellular level typically rely on rigid metals that poorly match the mechanical properties of soft brain tissue. As a result these electrodes often cause extensive acute and chronic injury, leading to short electrode lifetime. Recently, flexible electrodes such as Carbon Nanotube fibers (CNTf) have emerged as an attractive alternative to conventional electrodes and studies have shown that these flexible electrodes reduce neuro-inflammation and increase the quality and longevity of neural recordings. Insertion of these new compliant electrodes, however, remains challenge. The stiffening agents necessary to make the electrodes rigid enough to be inserted increases device footprint, which exacerbates brain damage during implantation. To overcome this challenge we have developed a novel technology to precisely implant and actuate high-performance, flexible carbon nanotube fiber (CNTf) microelectrodes without using a stiffening agents or shuttles. Instead, our technology uses drag forces within a microfluidic device to drive electrodes into tissue while minimizing the amount of fluid that is ejected into the tissue. In vitro experiments in brain phantoms, show that microfluidic actuated CNTf can be implanted at least 4.5 mm depth with 30 microm precision, while keeping the total volume of fluid ejected below 0.1 microL. As proof of concept, we inserted CNTfs in the small cnidarian Hydra littoralis and observed compound action potentials corresponding to contractions and in agreement with the literature. Additionally, brain slices extracted from transgenic mice were used to show that our device can be used to record spontaneous and light evoked activity from the cortex and deep brain regions such as the thalamic reticular nucleus (TRN). Overall our microfluidic actuation technology provides a platform for implanting and actuating flexible electrodes that significantly reduces damage during insertion.

Stimulation sites in the subthalamic nucleus projected onto a mean 3-D atlas of the thalamus and basal ganglia.

PubMed

Sarnthein, Johannes; Péus, Dominik; Baumann-Vogel, Heide; Baumann, Christian R; Sürücü, Oguzkan

2013-09-01

In patients with severe forms of Parkinson's disease (PD), deep brain stimulation (DBS) commonly targets the subthalamic nucleus (STN). Recently, the mean 3-D Morel-Atlas of the basal ganglia and the thalamus was introduced. It combines information contained in histological data from ten post-mortem brains. We were interested whether the Morel-Atlas is applicable for the visualization of stimulation sites. In a consecutive PD patient series, we documented preoperative MRI planning, intraoperative target adjustment based on electrophysiological and neurological testing, and perioperative CT target reconstruction. The localization of the DBS electrodes and the optimal stimulation sites were projected onto the Morel-Atlas. We included 20 patients (median age 62 years). The active contact had mean coordinates Xlat = ±12.1 mm, Yap = -1.8 mm, Zvert = -3.2 mm. There was a significant difference between the initially planned site and the coordinates of the postoperative active contact site (median 2.2 mm). The stimulation site was, on average, more anterior and more dorsal. The electrode contact used for optimal stimulation was found within the STN of the atlas in 38/40 (95 %) of implantations. The cluster of stimulation sites in individual patients-as deduced from preoperative MR, intraoperative electrophysiology and neurological testing-showed a high degree of congruence with the atlas. The mean 3D Morel Atlas is thus a useful tool for postoperative target visualization. This represents the first clinical evaluation of the recently created atlas.

Conduction aphasia as a function of the dominant posterior perisylvian cortex. Report of two cases.

PubMed

Quigg, Mark; Geldmacher, David S; Elias, W Jeff

2006-05-01

Assessment of eloquent functions during brain mapping usually relies on testing reading, speech, and comprehension to uncover transient deficits during electrical stimulation. These tests stem from findings predicted by the Geschwind-Wernicke hypothesis of receptive and expressive cortices connected by white matter tracts. Later work, however, has emphasized cortical mechanisms of language function. The authors report two cases that demonstrate that conduction aphasia is cortically mediated and can be inadequately assessed if not specifically evaluated during brain mapping. To determine the distribution of language on the dominant cortex, electrical cortical stimulation was performed in two cases by using implanted subdural electrodes during brain mapping before epilepsy surgery. A transient isolated deficit in repetition of language was reported during stimulation of the posterior portion of the dominant superior temporal gyrus in one patient and during stimulation of the supramarginal gyrus in the other patient. These cases demonstrate a localization of language repetition to the posterior perisylvian cortex. Brain mapping of this region should include assessment of verbal repetition to avoid potential deficits resembling conduction aphasia.

Optimization of focality and direction in dense electrode array transcranial direct current stimulation (tDCS)

NASA Astrophysics Data System (ADS)

Guler, Seyhmus; Dannhauer, Moritz; Erem, Burak; Macleod, Rob; Tucker, Don; Turovets, Sergei; Luu, Phan; Erdogmus, Deniz; Brooks, Dana H.

2016-06-01

Objective. Transcranial direct current stimulation (tDCS) aims to alter brain function non-invasively via electrodes placed on the scalp. Conventional tDCS uses two relatively large patch electrodes to deliver electrical current to the brain region of interest (ROI). Recent studies have shown that using dense arrays containing up to 512 smaller electrodes may increase the precision of targeting ROIs. However, this creates a need for methods to determine effective and safe stimulus patterns as the number of degrees of freedom is much higher with such arrays. Several approaches to this problem have appeared in the literature. In this paper, we describe a new method for calculating optimal electrode stimulus patterns for targeted and directional modulation in dense array tDCS which differs in some important aspects with methods reported to date. Approach. We optimize stimulus pattern of dense arrays with fixed electrode placement to maximize the current density in a particular direction in the ROI. We impose a flexible set of safety constraints on the current power in the brain, individual electrode currents, and total injected current, to protect subject safety. The proposed optimization problem is convex and thus efficiently solved using existing optimization software to find unique and globally optimal electrode stimulus patterns. Main results. Solutions for four anatomical ROIs based on a realistic head model are shown as exemplary results. To illustrate the differences between our approach and previously introduced methods, we compare our method with two of the other leading methods in the literature. We also report on extensive simulations that show the effect of the values chosen for each proposed safety constraint bound on the optimized stimulus patterns. Significance. The proposed optimization approach employs volume based ROIs, easily adapts to different sets of safety constraints, and takes negligible time to compute. An in-depth comparison study gives insight into the relationship between different objective criteria and optimized stimulus patterns. In addition, the analysis of the interaction between optimized stimulus patterns and safety constraint bounds suggests that more precise current localization in the ROI, with improved safety criterion, may be achieved by careful selection of the constraint bounds.

A systematic review of studies on anatomical position of electrode contacts used for chronic subthalamic stimulation in Parkinson's disease.

PubMed

Caire, François; Ranoux, Danièle; Guehl, Dominique; Burbaud, Pierre; Cuny, Emmanuel

2013-09-01

The dorso-lateral part of the subthalamic nucleus (STN) is considered as the usual target of deep brain stimulation for Parkinson's disease. Nevertheless, the exact anatomical location of the electrode contacts used for chronic stimulation is still a matter of debate. The aim of this study was to perform a systematic review of the existing literature on this issue. We searched for studies on the anatomical location of active contacts published until December 2012. We identified 13 studies, published between 2002 and 2010, including 260 patients and 466 electrodes. One hundred and sixty-four active contacts (35 %) were identified within the STN, 117 (25 %) at the interface between STN and the surrounding structures, 184 (40 %) above the STN and one within the substantia nigra. We observed great discrepancies between the different series. The contra-lateral improvement was between 37 and 78.5 % for contacts located within the STN, between 48.6 and 73 % outside the STN, between 65.3 and 66 % at the interface. The authors report no clear correlation between anatomical location and stimulation parameters. Post-operative analysis of the anatomical location of active contacts is difficult, and all the methods used are debatable. The relationship between the anatomical location of active contacts and the clinical effectiveness of stimulation is unclear. It would be necessary to take into account the volume of the electrode contacts and the diffusion of the stimulation. We can nevertheless assume that the interface between dorso-lateral STN, zona incerta and Forel's fields could be directly involved in the effects of stimulation.

Use of Computational Modeling to Inform tDCS Electrode Montages for the Promotion of Language Recovery in Post-stroke Aphasia.

PubMed

Galletta, Elizabeth E; Cancelli, Andrea; Cottone, Carlo; Simonelli, Ilaria; Tecchio, Franca; Bikson, Marom; Marangolo, Paola

2015-01-01

Although pilot trials of transcranial direct current stimulation (tDCS) in aphasia are encouraging, protocol optimization is needed. Notably, it has not yet been clarified which of the varied electrode montages investigated is the most effective in enhancing language recovery. To consider and contrast the predicted brain current flow patterns (electric field distribution) produced by varied 1×1 tDCS (1 anode, 1 cathode, 5 × 7 cm pad electrodes) montages used in aphasia clinical trials. A finite element model of the head of a single left frontal stroke patient was developed in order to study the pattern of the cortical EF magnitude and inward/outward radial EF under five different electrode montages: Anodal-tDCS (A-tDCS) over the left Wernicke's area (Montage A) and over the left Broca's area (Montage B); Cathodal tDCS (C-tDCS) over the right homologue of Wernicke's area (Montage C), and of Broca's area (Montage D), where for all montages A-D the "return" electrode was placed over the supraorbital contralateral forehead; bilateral stimulation with A-tDCS over the left Broca's and CtDCS over the right Broca's homologue (Montage E). In all cases, the "return" electrode over the contralesional supraorbital forehead was not inert and influenced the current path through the entire brain. Montage B, although similar to montage D in focusing the current in the perilesional area, exerted the greatest effect over the left perilesional cortex, which was even stronger in montage E. The position and influence of both electrodes must be considered in the design and interpretation of tDCS clinical trials for aphasia. Copyright © 2015 Elsevier Inc. All rights reserved.

PyDBS: an automated image processing workflow for deep brain stimulation surgery.

PubMed

D'Albis, Tiziano; Haegelen, Claire; Essert, Caroline; Fernández-Vidal, Sara; Lalys, Florent; Jannin, Pierre

2015-02-01

Deep brain stimulation (DBS) is a surgical procedure for treating motor-related neurological disorders. DBS clinical efficacy hinges on precise surgical planning and accurate electrode placement, which in turn call upon several image processing and visualization tasks, such as image registration, image segmentation, image fusion, and 3D visualization. These tasks are often performed by a heterogeneous set of software tools, which adopt differing formats and geometrical conventions and require patient-specific parameterization or interactive tuning. To overcome these issues, we introduce in this article PyDBS, a fully integrated and automated image processing workflow for DBS surgery. PyDBS consists of three image processing pipelines and three visualization modules assisting clinicians through the entire DBS surgical workflow, from the preoperative planning of electrode trajectories to the postoperative assessment of electrode placement. The system's robustness, speed, and accuracy were assessed by means of a retrospective validation, based on 92 clinical cases. The complete PyDBS workflow achieved satisfactory results in 92 % of tested cases, with a median processing time of 28 min per patient. The results obtained are compatible with the adoption of PyDBS in clinical practice.

Neuroversion: using electroconvulsive therapy as a bridge to deep brain stimulation implantation.

PubMed

Williams, Nolan R; Sahlem, Greg; Pannu, Jaspreet; Takacs, Istvan; Short, Baron; Revuelta, Gonzalo; George, Mark S

2017-02-01

Parkinson's disease (PD) is a movement disorder with significant neuropsychiatric comorbidities. Electroconvulsive therapy (ECT) is effective in treating these neuropsychiatric symptoms; however, clinicians are reluctant to use ECT in patients with deep brain stimulation (DBS) implantations for fear of damaging the device, as well as potential cognitive side effects. Right unilateral ultra-brief pulse (RUL UBP) ECT has a more favorable cognitive side-effect profile yet has never been reported in PD patients with DBS implants. We present a case series of three patients with a history of PD that all presented with psychiatric decompensation immediately prior to planned DBS surgery. All three patients had DBS electrode(s) in place at the time and an acute course of ECT was utilized in a novel method to "bridge" these individuals to neurosurgery. The patients all experienced symptom resolution (psychosis and/or depression and/or anxiety) without apparent cognitive side effects. This case series not only illustrates that right unilateral ultra-brief pulse can be utilized in patients with DBS electrodes but also illustrates that this intervention can be utilized as a neuromodulatory "bridge", where nonoperative surgical candidates with unstable psychiatric symptoms can be converted to operative candidates in a manner similar to electrical cardioversion.

A critical reflection on the technological development of deep brain stimulation (DBS)

PubMed Central

Ineichen, Christian; Glannon, Walter; Temel, Yasin; Baumann, Christian R.; Sürücü, Oguzkan

2014-01-01

Since the translational research findings of Benabid and colleagues which partly led to their seminal paper regarding the treatment of mainly tremor-dominant Parkinson patients through thalamic high-frequency-stimulation (HFS) in 1987, we still struggle with identifying a satisfactory mechanistic explanation of the underlying principles of deep brain stimulation (DBS). Furthermore, the technological advance of DBS devices (electrodes and implantable pulse generators, IPG’s) has shown a distinct lack of dynamic progression. In light of this we argue that it is time to leave the paleolithic age and enter hellenistic times: the device-manufacturing industry and the medical community together should put more emphasis on advancing the technology rather than resting on their laurels. PMID:25278864

Signal processing methods for reducing artifacts in microelectrode brain recordings caused by functional electrical stimulation

NASA Astrophysics Data System (ADS)

Young, D.; Willett, F.; Memberg, W. D.; Murphy, B.; Walter, B.; Sweet, J.; Miller, J.; Hochberg, L. R.; Kirsch, R. F.; Ajiboye, A. B.

2018-04-01

Objective. Functional electrical stimulation (FES) is a promising technology for restoring movement to paralyzed limbs. Intracortical brain-computer interfaces (iBCIs) have enabled intuitive control over virtual and robotic movements, and more recently over upper extremity FES neuroprostheses. However, electrical stimulation of muscles creates artifacts in intracortical microelectrode recordings that could degrade iBCI performance. Here, we investigate methods for reducing the cortically recorded artifacts that result from peripheral electrical stimulation. Approach. One participant in the BrainGate2 pilot clinical trial had two intracortical microelectrode arrays placed in the motor cortex, and thirty-six stimulating intramuscular electrodes placed in the muscles of the contralateral limb. We characterized intracortically recorded electrical artifacts during both intramuscular and surface stimulation. We compared the performance of three artifact reduction methods: blanking, common average reference (CAR) and linear regression reference (LRR), which creates channel-specific reference signals, composed of weighted sums of other channels. Main results. Electrical artifacts resulting from surface stimulation were 175  ×  larger than baseline neural recordings (which were 110 µV peak-to-peak), while intramuscular stimulation artifacts were only 4  ×  larger. The artifact waveforms were highly consistent across electrodes within each array. Application of LRR reduced artifact magnitudes to less than 10 µV and largely preserved the original neural feature values used for decoding. Unmitigated stimulation artifacts decreased iBCI decoding performance, but performance was almost completely recovered using LRR, which outperformed CAR and blanking and extracted useful neural information during stimulation artifact periods. Significance. The LRR method was effective at reducing electrical artifacts resulting from both intramuscular and surface FES, and almost completely restored iBCI decoding performance (>90% recovery for surface stimulation and full recovery for intramuscular stimulation). The results demonstrate that FES-induced artifacts can be easily mitigated in FES  +  iBCI systems by using LRR for artifact reduction, and suggest that the LRR method may also be useful in other noise reduction applications.

EKG-based detection of deep brain stimulation in fMRI studies.

PubMed

Fiveland, Eric; Madhavan, Radhika; Prusik, Julia; Linton, Renee; Dimarzio, Marisa; Ashe, Jeffrey; Pilitsis, Julie; Hancu, Ileana

2018-04-01

To assess the impact of synchronization errors between the assumed functional MRI paradigm timing and the deep brain stimulation (DBS) on/off cycling using a custom electrocardiogram-based triggering system METHODS: A detector for measuring and predicting the on/off state of cycling deep brain stimulation was developed and tested in six patients in office visits. Three-electrode electrocardiogram measurements, amplified by a commercial bio-amplifier, were used as input for a custom electronics box (e-box). The e-box transformed the deep brain stimulation waveforms into transistor-transistor logic pulses, recorded their timing, and propagated it in time. The e-box was used to trigger task-based deep brain stimulation functional MRI scans in 5 additional subjects; the impact of timing accuracy on t-test values was investigated in a simulation study using the functional MRI data. Following locking to each patient's individual waveform, the e-box was shown to predict stimulation onset with an average absolute error of 112 ± 148 ms, 30 min after disconnecting from the patients. The subsecond accuracy of the e-box in predicting timing onset is more than adequate for our slow varying, 30-/30-s on/off stimulation paradigm. Conversely, the experimental deep brain stimulation onset prediction accuracy in the absence of the e-box, which could be off by as much as 4 to 6 s, could significantly decrease activation strength. Using this detector, stimulation can be accurately synchronized to functional MRI acquisitions, without adding any additional hardware in the MRI environment. Magn Reson Med 79:2432-2439, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Recent Advances in Neural Electrode-Tissue Interfaces.

PubMed

Woeppel, Kevin; Yang, Qianru; Cui, Xinyan Tracy

2017-12-01

Neurotechnology is facing an exponential growth in the recent decades. Neural electrode-tissue interface research has been well recognized as an instrumental component of neurotechnology development. While satisfactory long-term performance was demonstrated in some applications, such as cochlear implants and deep brain stimulators, more advanced neural electrode devices requiring higher resolution for single unit recording or microstimulation still face significant challenges in reliability and longevity. In this article, we review the most recent findings that contribute to our current understanding of the sources of poor reliability and longevity in neural recording or stimulation, including the material failure, biological tissue response and the interplay between the two. The newly developed characterization tools are introduced from electrophysiology models, molecular and biochemical analysis, material characterization to live imaging. The effective strategies that have been applied to improve the interface are also highlighted. Finally, we discuss the challenges and opportunities in improving the interface and achieving seamless integration between the implanted electrodes and neural tissue both anatomically and functionally.

Transcranial Direct Current Stimulation Modulates Neuronal Networks in Attention Deficit Hyperactivity Disorder.

PubMed

Sotnikova, Anna; Soff, Cornelia; Tagliazucchi, Enzo; Becker, Katja; Siniatchkin, Michael

2017-09-01

Anodal transcranial direct current stimulation (tDCS) of the prefrontal cortex has been repeatedly shown to improve working memory (WM). Since patients with attention deficit hyperactivity disorder (ADHD) are characterized by both underactivation of the prefrontal cortex and deficits in WM, the modulation of prefrontal activity with tDCS in ADHD patients may increase their WM performance as well as improve the activation and connectivity of the WM network. In the present study, this hypothesis was tested using a double-blind sham-controlled experimental design. After randomization, sixteen adolescents with ADHD underwent either anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC, 1 mA, 20 min) or sham stimulation with simultaneous fMRI during n-back WM task. Both in one-back and two-back conditions, tDCS led to a greater activation (compared with sham stimulation) of the left DLPFC (under the electrode), left premotor cortex, left supplementary motor cortex, and precuneus. The effects of tDCS were long-lasting and influenced resting state functional connectivity even 20 min after the stimulation, with patterns of strengthened DLPFC connectivity after tDCS outlining the WM network. In summary, anodal tDCS caused increased neuronal activation and connectivity, not only in the brain area under the stimulating electrode (i.e. left DLPFC) but also in other, more remote brain regions. Because of moderate behavioral effects of tDCS, the significance of this technique for ADHD treatment has to be investigated in further studies.

Wide-bore 1.5 T MRI-guided deep brain stimulation surgery: initial experience and technique comparison.

PubMed

Sillay, Karl A; Rusy, Deborah; Buyan-Dent, Laura; Ninman, Nancy L; Vigen, Karl K

2014-12-01

We report results of the initial experience with magnetic resonance image (MRI)-guided implantation of subthalamic nucleus (STN) deep brain stimulating (DBS) electrodes at the University of Wisconsin after having employed frame-based stereotaxy with previously available MR imaging techniques and microelectrode recording for STN DBS surgeries. Ten patients underwent MRI-guided DBS implantation of 20 electrodes between April 2011 and March 2013. The procedure was performed in a purpose-built intraoperative MRI suite configured specifically to allow MRI-guided DBS, using a wide-bore (70 cm) MRI system. Trajectory guidance was accomplished with commercially available system consisting of an MR-visible skull-mounted aiming device and a software guidance system processing intraoperatively acquired iterative MRI scans. A total of 10 patients (5 male, 5 female)-representative of the Parkinson Disease (PD) population-were operated on with standard technique and underwent 20 electrode placements under MRI-guided bilateral STN-targeted DBS placement. All patients completed the procedure with electrodes successfully placed in the STN. Procedure time improved with experience. Our initial experience confirms the safety of MRI-guided DBS, setting the stage for future investigations combining physiology and MRI guidance. Further follow-up is required to compare the efficacy of the MRI-guided surgery cohort to that of traditional frame-based stereotaxy. Copyright © 2014 Elsevier B.V. All rights reserved.

Functional neurosurgery for movement disorders: a historical perspective.

PubMed

Benabid, Alim Louis; Chabardes, Stephan; Torres, Napoleon; Piallat, Brigitte; Krack, Paul; Fraix, Valerie; Pollak, Pierre

2009-01-01

Since the 1960s, deep brain stimulation and spinal cord stimulation at low frequency (30 Hz) have been used to treat intractable pain of various origins. For this purpose, specific hardware have been designed, including deep brain electrodes, extensions, and implantable programmable generators (IPGs). In the meantime, movement disorders, and particularly parkinsonian and essential tremors, were treated by electrolytic or mechanic lesions in various targets of the basal ganglia, particularly in the thalamus and in the internal pallidum. The advent in the 1960s of levodopa, as well as the side effects and complications of ablative surgery (e.g., thalamotomy and pallidotomy), has sent functional neurosurgery of movement disorders to oblivion. In 1987, the serendipitous discovery of the effect of high-frequency stimulation (HFS), mimicking lesions, allowed the revival of the surgery of movement disorders by stimulation of the thalamus, which treated tremors with limited morbidity, and adaptable and reversible results. The stability along time of these effects allowed extending it to new targets suggested by basic research in monkeys. The HFS of the subthalamic nucleus (STN) has profoundly challenged the practice of functional surgery as the effect on the triad of dopaminergic symptoms was very significant, allowing to decrease the drug dosage and therefore a decrease of their complications, the levodopa-induced dyskinesias. In the meantime, based on the results of previous basic research in various fields, HFS has been progressively extended to potentially treat epilepsy and, more recently, psychiatric disorders, such as obsessive-compulsive disorders, Gilles de la Tourette tics, and severe depression. Similarly, suggested by the observation of changes in PET scan, applications have been extended to cluster headaches by stimulation of the posterior hypothalamus and even more recently, to obesity and drug addiction. In the field of movement disorders, it has become clear that STN stimulation is not efficient on the nondopaminergic symptoms such as freezing of gait. Based on experimental data obtained in MPTP-treated parkinsonian monkeys, the pedunculopontine nucleus has been used as a new target, and as suggested by the animal research results, its use indeed improves walking and stability when stimulation is performed at low frequency (25 Hz). The concept of simultaneous stimulation of multiple targets eventually at low or high frequency, and that of several electrodes in one target, is being accepted to increase the efficiency. This leads to and is being facilitated by the development of new hardware (multiple-channel IPGs, specific electrodes, rechargeable batteries). Still additional efforts are needed at the level of the stimulation paradigm and in the waveform. The recent development of nanotechnologies allows the design of totally new systems expanding the field of deep brain stimulation. These new techniques will make it possible to not only inhibit or excite deep brain structures to alleviate abnormal symptoms but also open the field for the use of recording cortical activities to drive neuroprostheses through brain-computer interfaces. The new field of compensation of deficits will then become part of the field of functional neurosurgery.

Enhanced detection threshold for in vivo cortical stimulation produced by Hebbian conditioning

NASA Astrophysics Data System (ADS)

Rebesco, James M.; Miller, Lee E.

2011-02-01

Normal brain function requires constant adaptation, as an organism learns to associate important sensory stimuli with the appropriate motor actions. Neurological disorders may disrupt these learned associations and require the nervous system to reorganize itself. As a consequence, neural plasticity is a crucial component of normal brain function and a critical mechanism for recovery from injury. Associative, or Hebbian, pairing of pre- and post-synaptic activity has been shown to alter stimulus-evoked responses in vivo; however, to date, such protocols have not been shown to affect the animal's subsequent behavior. We paired stimulus trains separated by a brief time delay to two electrodes in rat sensorimotor cortex, which changed the statistical pattern of spikes during subsequent behavior. These changes were consistent with strengthened functional connections from the leading electrode to the lagging electrode. We then trained rats to respond to a microstimulation cue, and repeated the paradigm using the cue electrode as the leading electrode. This pairing lowered the rat's ICMS-detection threshold, with the same dependence on intra-electrode time lag that we found for the functional connectivity changes. The timecourse of the behavioral effects was very similar to that of the connectivity changes. We propose that the behavioral changes were a consequence of strengthened functional connections from the cue electrode to other regions of sensorimotor cortex. Such paradigms might be used to augment recovery from a stroke, or to promote adaptation in a bidirectional brain-machine interface.

Medical devices of the head, neck, and spine.

PubMed

Hunter, Tim B; Yoshino, Mark T; Dzioba, Robert B; Light, Rick A; Berger, William G

2004-01-01

There are many medical devices used for head, neck, and spinal diseases and injuries, and new devices are constantly being introduced. Many of the newest devices are variations on a previous theme. Knowing the specific name of a device is not important. It is important to recognize the presence of a device and to have an understanding of its function as well as to be able to recognize the complications associated with its use. The article discusses the most common and important devices of the head, neck, and spine, including cerebrospinal fluid shunts and the Codman Hakim programmable valve; subdural drainage catheters, subdural electrodes, intracranial electrodes, deep brain stimulators, and cerebellar electrodes; coils, balloons, adhesives, particles, and aneurysm clips; radiation therapy catheters, intracranial balloons for drug installation, and carmustine wafers; hearing aids, cochlear implants, and ossicular reconstruction prostheses; orbital prostheses, intraocular silicone oil, and lacrimal duct stents; anterior and posterior cervical plates, posterior cervical spine wiring, odontoid fracture fixation devices, cervical collars and halo vests; thoracic and lumbar spine implants, anterior and posterior instrumentation for the thoracic and lumbar spine, vertebroplasty, and artificial disks; spinal column stimulators, bone stimulators, intrathecal drug delivery pumps, and sacral stimulators; dental and facial implant devices; gastric and tracheal tubes; vagus nerve stimulators; lumboperitoneal shunts; and temperature- and oxygen-sensing probes. Copyright RSNA, 2004

Prefrontal transcranial direct current stimulation alters activation and connectivity in cortical and subcortical reward systems: a tDCS-fMRI study.

PubMed

Weber, Matthew J; Messing, Samuel B; Rao, Hengyi; Detre, John A; Thompson-Schill, Sharon L

2014-08-01

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique used both experimentally and therapeutically to modulate regional brain function. However, few studies have directly measured the aftereffects of tDCS on brain activity or examined changes in task-related brain activity consequent to prefrontal tDCS. To investigate the neural effects of tDCS, we collected fMRI data from 22 human subjects, both at rest and while performing the Balloon Analog Risk Task (BART), before and after true or sham transcranial direct current stimulation. TDCS decreased resting blood perfusion in orbitofrontal cortex and the right caudate and increased task-related activity in the right dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in response to losses but not wins or increasing risk. Network analysis showed that whole-brain connectivity of the right ACC correlated positively with the number of pumps subjects were willing to make on the BART, and that tDCS reduced connectivity between the right ACC and the rest of the brain. Whole-brain connectivity of the right DLPFC also correlated negatively with pumps on the BART, as prior literature would suggest. Our results suggest that tDCS can alter activation and connectivity in regions distal to the electrodes. Copyright © 2014 Wiley Periodicals, Inc.

Use of functional near-infrared spectroscopy to monitor cortical plasticity induced by transcranial direct current stimulation

NASA Astrophysics Data System (ADS)

Khan, Bilal; Hervey, Nathan; Stowe, Ann; Hodics, Timea; Alexandrakis, George

2013-03-01

Electrical stimulation of the human cortex in conjunction with physical rehabilitation has been a valuable approach in facilitating the plasticity of the injured brain. One such method is transcranial direct current stimulation (tDCS) which is a non-invasive method to elicit neural stimulation by delivering current through electrodes placed on the scalp. In order to better understand the effects tDCS has on cortical plasticity, neuroimaging techniques have been used pre and post tDCS stimulation. Recently, neuroimaging methods have discovered changes in resting state cortical hemodynamics after the application of tDCS on human subjects. However, analysis of the cortical hemodynamic activity for a physical task during and post tDCS stimulation has not been studied to our knowledge. A viable and sensitive neuroimaging method to map changes in cortical hemodynamics during activation is functional near-infrared spectroscopy (fNIRS). In this study, the cortical activity during an event-related, left wrist curl task was mapped with fNIRS before, during, and after tDCS stimulation on eight healthy adults. Along with the fNIRS optodes, two electrodes were placed over the sensorimotor hand areas of both brain hemispheres to apply tDCS. Changes were found in both resting state cortical connectivity and cortical activation patterns that occurred during and after tDCS. Additionally, changes to surface electromyography (sEMG) measurements of the wrist flexor and extensor of both arms during the wrist curl movement, acquired concurrently with fNIRS, were analyzed and related to the transient cortical plastic changes induced by tDCS.

Clinical Phenotype Predicts Early Staged Bilateral Deep Brain Stimulation in Parkinson’s Disease

PubMed Central

Sung, Victor W.; Watts, Ray L.; Schrandt, Christian J.; Guthrie, Stephanie; Wang, Deli; Amara, Amy W.; Guthrie, Barton L.; Walker, Harrison C.

2014-01-01

Object While many centers place bilateral DBS systems simultaneously, unilateral STN DBS followed by a staged contralateral procedure has emerged as a treatment option for many patients. However little is known about whether the preoperative phenotype predicts when staged placement of a DBS electrode in the opposite subthalamic nucleus will be required. We aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second subthalamic deep brain stimulation (DBS) electrode in patients who undergo unilateral subthalamic DBS for Parkinson's disease (PD). Methods Eighty-two consecutive patients with advanced PD underwent unilateral subthalamic DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression determined preoperative characteristics that predicted staged placement of a second electrode in the opposite subthalamic nucleus. Preoperative measurements included aspects of the Unified Parkinson Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. Results At 2 years follow-up, 28 of the 82 patients (34%) had undergone staged placement of a contralateral electrode while the remainder chose to continue with unilateral stimulation. Statistically significant improvements in UPDRS total and part 3 scores were retained at the end of the 2 year follow-up period in both subsets of patients. Multivariate logistic regression showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (odds ratio 13.4; 95% confidence interval 2.8, 64.9), high tremor subscore (OR 7.2; CI 1.5, 35.0), and low body weight (OR 5.5; CI 1.4, 22.3). Conclusions This single center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral subthalamic DBS. These data may aid in the management of patients with advanced PD who undergo subthalamic DBS. PMID:24074493

Microelectrode Recordings Validate the Clinical Visualization of Subthalamic-Nucleus Based on 7T Magnetic Resonance Imaging and Machine Learning for Deep Brain Stimulation Surgery.

PubMed

Shamir, Reuben R; Duchin, Yuval; Kim, Jinyoung; Patriat, Remi; Marmor, Odeya; Bergman, Hagai; Vitek, Jerrold L; Sapiro, Guillermo; Bick, Atira; Eliahou, Ruth; Eitan, Renana; Israel, Zvi; Harel, Noam

2018-05-24

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a proven and effective therapy for the management of the motor symptoms of Parkinson's disease (PD). While accurate positioning of the stimulating electrode is critical for success of this therapy, precise identification of the STN based on imaging can be challenging. We developed a method to accurately visualize the STN on a standard clinical magnetic resonance imaging (MRI). The method incorporates a database of 7-Tesla (T) MRIs of PD patients together with machine-learning methods (hereafter 7 T-ML). To validate the clinical application accuracy of the 7 T-ML method by comparing it with identification of the STN based on intraoperative microelectrode recordings. Sixteen PD patients who underwent microelectrode-recordings guided STN DBS were included in this study (30 implanted leads and electrode trajectories). The length of the STN along the electrode trajectory and the position of its contacts to dorsal, inside, or ventral to the STN were compared using microelectrode-recordings and the 7 T-ML method computed based on the patient's clinical 3T MRI. All 30 electrode trajectories that intersected the STN based on microelectrode-recordings, also intersected it when visualized with the 7 T-ML method. STN trajectory average length was 6.2 ± 0.7 mm based on microelectrode recordings and 5.8 ± 0.9 mm for the 7 T-ML method. We observed a 93% agreement regarding contact location between the microelectrode-recordings and the 7 T-ML method. The 7 T-ML method is highly consistent with microelectrode-recordings data. This method provides a reliable and accurate patient-specific prediction for targeting the STN.

Cortical visual evoked potentials recorded after optic tract near field stimulation during GPi-DBS in non-cooperative patients.

PubMed

Landi, Andrea; Pirillo, David; Cilia, Roberto; Antonini, Angelo; Sganzerla, Erik P

2011-02-01

Neurophysiologic monitoring during deep brain stimulation (DBS) interventions in the globus pallidus internum (Gpi) for the treatment of Parkinson's disease or primary dystonia is generally based upon microelectrode recordings (MER); moreover, MER request sophisticated technology and high level trained personnel for a reliable monitoring. Recordings of cortical visual evoked potentials (CVEPs) obtained after stimulation of the optic tract may be a potential option to MER; since optic tract lies just beneath the best target for Gpi DBS, changes in CVEPs during intraoperative exploration may drive a correct electrode positioning. Cortical VEPs from optic tract stimulation (OT C-CEPs) have been recorded in seven patients during GPi-DBS for the treatment of Parkinson's disease and primary dystonia under general sedation. OT C-VEPs were obtained after near-field monopolar stimulation of the optic tract; recording electrodes were at the scalp. Cortical responses after optic tract versus standard visual stimulation were compared. After intraoperative near-field OT stimulation a biphasic wave, named N40-P70, was detected in all cases. N40-P70 neither change in morphology nor in latency at different depths, but increased in amplitude approaching the optic tract. The electrode tip was positioned just 1mm above the point where OT-CVEPs showed the larger amplitude. No MERs were obtained in these patients; OT CVEPs were the only method to detect the Gpi before positioning the electrodes. OT CVEPs seem to be as reliable as MER to detail the optimal target in Gpi surgery: in addition they are less expensive, faster to perform and easier to decode. Copyright © 2010. Published by Elsevier B.V.

Electroencephalographic responses to ionizing radiation.

PubMed

GARCIA, J; BUCHWALD, N A; BACH-Y-RITA, G; FEDER, B H; KOELLING, R A

1963-04-19

Electroencephalographic recordings made from chronically implanted cortical electrodes indicate that ionizing radiation has an immediate effect upon brain wave patterns. X-rays delivered at the rate of 0.2 roentgen per second produce an arousal effect resembling that which occurs as a result of stimulation through peripheral receptor systems.

Long-Term Effective Thalamic Deep Brain Stimulation for Neuropathic Tremor in Two Patients with Charcot-Marie-Tooth Disease.

PubMed

Cabañes-Martínez, Lidia; Del Álamo de Pedro, Marta; de Blas Beorlegui, Gema; Bailly-Bailliere, Ignacio Regidor

2017-01-01

It has been described that many Charcot-Marie-Tooth syndrome type 2 patients are affected by a very disabling type of tremor syndrome, the pathophysiology of which remains unclear. Deep brain stimulation (DBS) has been successfully applied to treat most types of tremors by implanting electrodes in the ventral intermediate nucleus of the thalamus (Vim). We used DBS applied to the Vim in 2 patients with severe axonal inherited polyneuropathies who developed a disabling tremor. Both patients responded positively to stimulation, with a marked reduction of the tremor and with an improvement of their quality of life. We report 2 cases of tremor associated with a hereditary neuropathy with a good response to DBS. © 2017 S. Karger AG, Basel.

Neural prostheses in clinical applications--trends from precision mechanics towards biomedical microsystems in neurological rehabilitation.

PubMed

Stieglitz, T; Schuettler, M; Koch, K P

2004-04-01

Neural prostheses partially restore body functions by technical nerve excitation after trauma or neurological diseases. External devices and implants have been developed since the early 1960s for many applications. Several systems have reached nowadays clinical practice: Cochlea implants help the deaf to hear, micturition is induced by bladder stimulators in paralyzed persons and deep brain stimulation helps patients with Parkinson's disease to participate in daily life again. So far, clinical neural prostheses are fabricated with means of precision mechanics. Since microsystem technology opens the opportunity to design and develop complex systems with a high number of electrodes to interface with the nervous systems, the opportunity for selective stimulation and complex implant scenarios seems to be feasible in the near future. The potentials and limitations with regard to biomedical microdevices are introduced and discussed in this paper. Target specifications are derived from existing implants and are discussed on selected applications that has been investigated in experimental research: a micromachined implant to interface a nerve stump with a sieve electrode, cuff electrodes with integrated electronics, and an epiretinal vision prosthesis.

Characterization of oscillatory changes in hippocampus and amygdala after deep brain stimulation of the infralimbic prefrontal cortex.

PubMed

Cervera-Ferri, Ana; Teruel-Martí, Vicent; Barceló-Molina, Moises; Martínez-Ricós, Joana; Luque-García, Aina; Martínez-Bellver, Sergio; Adell, Albert

2016-07-01

Deep brain stimulation (DBS) is a new investigational therapy that has generated positive results in refractory depression. Although the neurochemical and behavioral effects of DBS have been examined, less attention has been paid to the influence of DBS on the network dynamics between different brain areas, which could contribute to its therapeutic effects. Herein, we set out to identify the effects of 1 h DBS in the infralimbic cortex (IL) on the oscillatory network dynamics between hippocampus and basolateral amygdala (BLA), two regions implicated in depression and its treatment. Urethane-anesthetized rats with bilaterally implanted electrodes in the IL were exposed to 1 h constant stimulation of 130 Hz of frequency, 60 μA of constant current intensity and biphasic pulse width of 80 μsec. After a period of baseline recording, local field potentials (LFP) were recorded with formvar-insulated stainless steel electrodes. DBS of the IL increased the power of slow wave (SW, <1.5 Hz) and theta (3-12 Hz) frequencies in the hippocampus and BLA Furthermore, IL DBS caused a precise coupling in different frequency bands between both brain structures. The increases in SW band synchronization in hippocampus and BLA after DBS suggest that these changes may be important for the improvement of depressive behavior. In addition, the augmentation in theta synchrony might contribute to improvement in emotional and cognitive processes. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Ownership of an artificial limb induced by electrical brain stimulation

PubMed Central

Collins, Kelly L.; Cronin, Jeneva; Olson, Jared D.; Ehrsson, H. Henrik; Ojemann, Jeffrey G.

2017-01-01

Replacing the function of a missing or paralyzed limb with a prosthetic device that acts and feels like one’s own limb is a major goal in applied neuroscience. Recent studies in nonhuman primates have shown that motor control and sensory feedback can be achieved by connecting sensors in a robotic arm to electrodes implanted in the brain. However, it remains unknown whether electrical brain stimulation can be used to create a sense of ownership of an artificial limb. In this study on two human subjects, we show that ownership of an artificial hand can be induced via the electrical stimulation of the hand section of the somatosensory (SI) cortex in synchrony with touches applied to a rubber hand. Importantly, the illusion was not elicited when the electrical stimulation was delivered asynchronously or to a portion of the SI cortex representing a body part other than the hand, suggesting that multisensory integration according to basic spatial and temporal congruence rules is the underlying mechanism of the illusion. These findings show that the brain is capable of integrating “natural” visual input and direct cortical-somatosensory stimulation to create the multisensory perception that an artificial limb belongs to one’s own body. Thus, they serve as a proof of concept that electrical brain stimulation can be used to “bypass” the peripheral nervous system to induce multisensory illusions and ownership of artificial body parts, which has important implications for patients who lack peripheral sensory input due to spinal cord or nerve lesions. PMID:27994147

A microfluidic brain slice perfusion chamber for multisite recording using penetrating electrodes.

PubMed

Blake, Alexander J; Rodgers, Frank C; Bassuener, Anna; Hippensteel, Joseph A; Pearce, Thomas M; Pearce, Timothy R; Zarnowska, Ewa D; Pearce, Robert A; Williams, Justin C

2010-05-30

To analyze the spatiotemporal dynamics of network activity in a brain tissue slice, it is useful to record simultaneously from multiple locations. When obtained from laminar structures such as the hippocampus or neocortex, multisite recordings also yield information about subcellular current distributions via current source density analysis. Multisite probes developed for in vivo recordings could serve these purposes in vitro, allowing recordings to be obtained from brain slices at sites deeper within the tissue than currently available surface recording methods permit. However, existing recording chambers do not allow for the insertion of lamina-spanning probes that enter through the edges of brain slices. Here, we present a novel brain slice recording chamber design that accomplishes this goal. The device provides a stable microfluidic perfusion environment in which tissue health is optimized by superfusing both surfaces of the slice. Multichannel electrodes can be inserted parallel to the surface of the slice, at any depth relative to the surface. Access is also provided from above for the insertion of additional recording or stimulating electrodes. We illustrate the utility of this recording configuration by measuring current sources and sinks during theta burst stimuli that lead to the induction of long-term potentiation in hippocampal slices. (c) 2010 Elsevier B.V. All rights reserved.

Deep brain stimulation during early adolescence prevents microglial alterations in a model of maternal immune activation.

PubMed

Hadar, Ravit; Dong, Le; Del-Valle-Anton, Lucia; Guneykaya, Dilansu; Voget, Mareike; Edemann-Callesen, Henriette; Schweibold, Regina; Djodari-Irani, Anais; Goetz, Thomas; Ewing, Samuel; Kettenmann, Helmut; Wolf, Susanne A; Winter, Christine

2017-07-01

In recent years schizophrenia has been recognized as a neurodevelopmental disorder likely involving a perinatal insult progressively affecting brain development. The poly I:C maternal immune activation (MIA) rodent model is considered as a neurodevelopmental model of schizophrenia. Using this model we and others demonstrated the association between neuroinflammation in the form of altered microglia and a schizophrenia-like endophenotype. Therapeutic intervention using the anti-inflammatory drug minocycline affected altered microglia activation and was successful in the adult offspring. However, less is known about the effect of preventive therapeutic strategies on microglia properties. Previously we found that deep brain stimulation of the medial prefrontal cortex applied pre-symptomatically to adolescence MIA rats prevented the manifestation of behavioral and structural deficits in adult rats. We here studied the effects of deep brain stimulation during adolescence on microglia properties in adulthood. We found that in the hippocampus and nucleus accumbens, but not in the medial prefrontal cortex, microglial density and soma size were increased in MIA rats. Pro-inflammatory cytokine mRNA was unchanged in all brain areas before and after implantation and stimulation. Stimulation of either the medial prefrontal cortex or the nucleus accumbens normalized microglia density and soma size in main projection areas including the hippocampus and in the area around the electrode implantation. We conclude that in parallel to an alleviation of the symptoms in the rat MIA model, deep brain stimulation has the potential to prevent the neuroinflammatory component in this disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Chronic transcranial focal stimulation from tripolar concentric ring electrodes does not disrupt memory formation in rats.

PubMed

Luby, Matthew D; Makeyev, Oleksandr; Besio, Walter G

2014-01-01

Non-invasive electrical brain stimulation has shown potential utility as a treatment for seizures in epilepsy patients. Transcranial focal stimulation (TFS) via tripolar concentric ring electrodes (TCREs) has been effective in reducing seizure severity in acute rodent models, but it has yet to be determined whether or not it will serve as a viable long-term treatment strategy. Prior experiments indicate that a single dose of TFS via TCRE does not impact short- or long-term memory formation. The present study investigated if five daily doses of TFS via a TCRE on the scalp affected the memory. The spontaneous object recognition (SOR) test was used to evaluate the memory. Sham and TFS-treated groups were evaluated and both showed comparable levels of preference for novel objects, indicating successful memory formation. More work on repeated dosage strategies is important for establishing the safety and efficacy of TFS as a putative treatment.

Fabrication of self-expandable NiTi thin film devices with micro-electrode array for bioelectric sensing, stimulation and ablation.

PubMed

Bechtold, Christoph; de Miranda, Rodrigo Lima; Chluba, Christoph; Quandt, Eckhard

2016-12-01

Self-expandable medical devices provide mechanical functionality at a specific location of the human body and are viable for minimal invasive procedures. Besides radiopaque markers and drug-eluting coatings, next generation self-expandable devices can be equipped with additional functionality, such as conductive and flexible electrodes, which enables chronic recording of bioelectrical signals, stimulating or ablating tissue. This promises new therapeutic options in various medical fields, among them in particular neuromodulation (e.g. deep brain stimulation), BioMEMS, radio frequency ablation, mapping or denervation. However, the fabrication of such multi-functional devices is challenging. For this study we have realized a 35 μm thick, superelastic NiTi thin film stent structure with six isolated electrodes on the outer circumference, each electrode connected to a contact pad at the end of the stent structure, using magnetron sputtering, UV lithography and wet chemical etching. Mechanical and electrical properties of the device during typical loading conditions, i.e. crimping, simulated pulsatile and electrochemical testing, were characterized and reveal promising results. For the fabrication of future multifunctional, minimal invasive medical devices, such as electroceuticals or other intelligent implants, NiTi thin film technology is therefore a versatile alternative to conventional fabrication routes.

Stimulating the Comfort of Textile Electrodes in Wearable Neuromuscular Electrical Stimulation.

PubMed

Zhou, Hui; Lu, Yi; Chen, Wanzhen; Wu, Zhen; Zou, Haiqing; Krundel, Ludovic; Li, Guanglin

2015-07-16

Textile electrodes are becoming an attractive means in the facilitation of surface electrical stimulation. However, the stimulation comfort of textile electrodes and the mechanism behind stimulation discomfort is still unknown. In this study, a textile stimulation electrode was developed using conductive fabrics and then its impedance spectroscopy, stimulation thresholds, and stimulation comfort were quantitatively assessed and compared with those of a wet textile electrode and a hydrogel electrode on healthy subjects. The equivalent circuit models and the finite element models of different types of electrode were built based on the measured impedance data of the electrodes to reveal the possible mechanism of electrical stimulation pain. Our results showed that the wet textile electrode could achieve similar stimulation performance as the hydrogel electrode in motor threshold and stimulation comfort. However, the dry textile electrode was found to have very low pain threshold and induced obvious cutaneous painful sensations during stimulation, in comparison to the wet and hydrogel electrodes. Indeed, the finite element modeling results showed that the activation function along the z direction at the depth of dermis epidermis junction of the dry textile electrode was significantly larger than that of the wet and hydrogel electrodes, thus resulting in stronger activation of pain sensing fibers. Future work will be done to make textile electrodes have similar stimulation performance and comfort as hydrogel electrodes.

Stimulating the Comfort of Textile Electrodes in Wearable Neuromuscular Electrical Stimulation

PubMed Central

Zhou, Hui; Lu, Yi; Chen, Wanzhen; Wu, Zhen; Zou, Haiqing; Krundel, Ludovic; Li, Guanglin

2015-01-01

Textile electrodes are becoming an attractive means in the facilitation of surface electrical stimulation. However, the stimulation comfort of textile electrodes and the mechanism behind stimulation discomfort is still unknown. In this study, a textile stimulation electrode was developed using conductive fabrics and then its impedance spectroscopy, stimulation thresholds, and stimulation comfort were quantitatively assessed and compared with those of a wet textile electrode and a hydrogel electrode on healthy subjects. The equivalent circuit models and the finite element models of different types of electrode were built based on the measured impedance data of the electrodes to reveal the possible mechanism of electrical stimulation pain. Our results showed that the wet textile electrode could achieve similar stimulation performance as the hydrogel electrode in motor threshold and stimulation comfort. However, the dry textile electrode was found to have very low pain threshold and induced obvious cutaneous painful sensations during stimulation, in comparison to the wet and hydrogel electrodes. Indeed, the finite element modeling results showed that the activation function along the z direction at the depth of dermis epidermis junction of the dry textile electrode was significantly larger than that of the wet and hydrogel electrodes, thus resulting in stronger activation of pain sensing fibers. Future work will be done to make textile electrodes have similar stimulation performance and comfort as hydrogel electrodes. PMID:26193273

One-pass deep brain stimulation of dentato-rubro-thalamic tract and subthalamic nucleus for tremor-dominant or equivalent type Parkinson's disease.

PubMed

Coenen, Volker Arnd; Rijntjes, Michel; Prokop, Thomas; Piroth, Tobias; Amtage, Florian; Urbach, Horst; Reinacher, Peter Christoph

2016-04-01

Refractory tremor in tremor-dominant (TD) or equivalent-type (EQT) idiopathic Parkinson's syndrome (IPS) poses the challenge of choosing the best target region to for deep brain stimulation (DBS). While the subthalamic nucleus is typically chosen in younger patients as the target for dopamine-responsive motor symptoms, it is more complicated if tremor does not (fully) respond under trial conditions. In this report, we present the first results from simultaneous bilateral DBS of the DRT (dentato-rubro-thalamic tract) and the subthalamic nucleus (STN) in two elderly patients with EQT and TD IPS and dopamine-refractory tremor. Two patients received bilateral octopolar DBS electrodes in the STN additionally traversing the DRT region. Achieved electrode positions were determined with helical CT, overlaid onto DTI tractography data, and compared with clinical data of stimulation response. Both patients showed immediate and sustained improvement of their tremor, bilaterally. The proposed approach appears to be safe and feasible and a combined stimulation of the two target regions was performed tailored to the patients' symptoms. Clinically, no neuropsychiatric effects were seen. Our pilot data suggest a viable therapeutic option to treat the subgroup of TD and EQT IPS and with tremor as the predominant symptom. A clinical study to further investigate this approach ( www.clinicaltrials.gov ; NCT02288468) is the focus of our ongoing research.

Flight behavior of the rhinoceros beetle Trypoxylus dichotomus during electrical nerve stimulation.

PubMed

Van Truong, Tien; Byun, Doyoung; Lavine, Laura Corley; Emlen, Douglas J; Park, Hoon Cheol; Kim, Min Jun

2012-09-01

Neuronal stimulation is an intricate part of understanding insect flight behavior and control insect itself. In this study, we investigated the effects of electrical pulses applied to the brain and basalar muscle of the rhinoceros beetle (Trypoxylus dichotomus). To understand specific neuronal stimulation mechanisms, responses and flight behavior of the beetle, four electrodes were implanted into the two optic lobes, the brain's central complex and the ventral nerve cord in the posterior pronotum. We demonstrated flight initiation, turning and cessation by stimulating the brain. The change undergone by the wing flapping in response to the electrical signal was analyzed from a sequence of images captured by a high-speed camera. Here, we provide evidence to distinguish the important differences between neuronal and muscular flight stimulations in beetles. We found that in the neural potential stimulation, both the hind wing and the elytron were suppressed. Interestingly, the beetle stopped flying whenever a stimulus potential was applied between the pronotum and one side of the optic lobe, or between the ventral nerve cord in the posterior pronotum and the central complex. In-depth experimentation demonstrated the effective of neural stimulation over muscle stimulation for flight control. During electrical stimulation of the optic lobes, the beetle performed unstable flight, resulting in alternating left and right turns. By applying the electrical signal into both the optic lobes and the central complex of the brain, we could precisely control the direction of the beetle flight. This work provides an insight into insect flight behavior for future development of insect-micro air vehicle.

Direct Electrical Stimulation of the Human Entorhinal Region and Hippocampus Impairs Memory.

PubMed

Jacobs, Joshua; Miller, Jonathan; Lee, Sang Ah; Coffey, Tom; Watrous, Andrew J; Sperling, Michael R; Sharan, Ashwini; Worrell, Gregory; Berry, Brent; Lega, Bradley; Jobst, Barbara C; Davis, Kathryn; Gross, Robert E; Sheth, Sameer A; Ezzyat, Youssef; Das, Sandhitsu R; Stein, Joel; Gorniak, Richard; Kahana, Michael J; Rizzuto, Daniel S

2016-12-07

Deep brain stimulation (DBS) has shown promise for treating a range of brain disorders and neurological conditions. One recent study showed that DBS in the entorhinal region improved the accuracy of human spatial memory. Based on this line of work, we performed a series of experiments to more fully characterize the effects of DBS in the medial temporal lobe on human memory. Neurosurgical patients with implanted electrodes performed spatial and verbal-episodic memory tasks. During the encoding periods of both tasks, subjects received electrical stimulation at 50 Hz. In contrast to earlier work, electrical stimulation impaired memory performance significantly in both spatial and verbal tasks. Stimulation in both the entorhinal region and hippocampus caused decreased memory performance. These findings indicate that the entorhinal region and hippocampus are causally involved in human memory and suggest that refined methods are needed to use DBS in these regions to improve memory. Copyright © 2016 Elsevier Inc. All rights reserved.

Computational Modeling and Neuroimaging Techniques for Targeting during Deep Brain Stimulation

PubMed Central

Sweet, Jennifer A.; Pace, Jonathan; Girgis, Fady; Miller, Jonathan P.

2016-01-01

Accurate surgical localization of the varied targets for deep brain stimulation (DBS) is a process undergoing constant evolution, with increasingly sophisticated techniques to allow for highly precise targeting. However, despite the fastidious placement of electrodes into specific structures within the brain, there is increasing evidence to suggest that the clinical effects of DBS are likely due to the activation of widespread neuronal networks directly and indirectly influenced by the stimulation of a given target. Selective activation of these complex and inter-connected pathways may further improve the outcomes of currently treated diseases by targeting specific fiber tracts responsible for a particular symptom in a patient-specific manner. Moreover, the delivery of such focused stimulation may aid in the discovery of new targets for electrical stimulation to treat additional neurological, psychiatric, and even cognitive disorders. As such, advancements in surgical targeting, computational modeling, engineering designs, and neuroimaging techniques play a critical role in this process. This article reviews the progress of these applications, discussing the importance of target localization for DBS, and the role of computational modeling and novel neuroimaging in improving our understanding of the pathophysiology of diseases, and thus paving the way for improved selective target localization using DBS. PMID:27445709

Cranial electrotherapy stimulation for treatment of anxiety, depression, and insomnia.

PubMed

Kirsch, Daniel L; Nichols, Francine

2013-03-01

Cranial electrotherapy stimulation is a prescriptive medical device that delivers a mild form of electrical stimulation to the brain for the treatment of anxiety, depression, and insomnia. It is supported by more than 40 years of research demonstrating its effectiveness in several mechanistic studies and greater than 100 clinical studies. Adverse effects are rare (<1%), mild, and self-limiting, consisting mainly of skin irritation under the electrodes and headaches. Often used as a stand-alone therapy, because results are usually seen from the first treatment, cranial electrotherapy stimulation may also be used as an adjunctive therapy. Copyright © 2013 Elsevier Inc. All rights reserved.

Deep Brain Stimulation of the Memory Circuit: Improving Cognition in Alzheimer's Disease.

PubMed

Posporelis, Sotirios; David, Anthony S; Ashkan, Keyoumars; Shotbolt, Paul

2018-05-26

Deep brain stimulation (DBS) is an effective invasive treatment for a wide range of neurological and psychiatric disorders. Neurosurgically implanted electrodes deliver stimulation of pre-programmed amplitude, frequency, and pulse width within deep brain structures; those settings can be adjusted at a later stage according to individual needs for optimal response. This results in variable effects dependent on the targeted region. An established treatment for movement disorders, the effectiveness of DBS in dementia remains under investigation. Translational studies have uncovered a pro-cognitive effect mediated by changes on cellular as well as network level. Several groups have attempted to examine the benefits of DBS in Alzheimer's disease; differences in inclusion criteria and methodology make generalization of results difficult. This review aims to summarize all completed and ongoing human studies of DBS in Alzheimer's disease. The results are classified by targeted anatomical structure. Future directions, as well as economical and ethical arguments, are explored in the final section.

Characterization of sputtered iridium oxide thin films on planar and laser micro-structured platinum thin film surfaces for neural stimulation applications

NASA Astrophysics Data System (ADS)

Thanawala, Sachin

Electrical stimulation of neurons provides promising results for treatment of a number of diseases and for restoration of lost function. Clinical examples include retinal stimulation for treatment of blindness and cochlear implants for deafness and deep brain stimulation for treatment of Parkinsons disease. A wide variety of materials have been tested for fabrication of electrodes for neural stimulation applications, some of which are platinum and its alloys, titanium nitride, and iridium oxide. In this study iridium oxide thin films were sputtered onto laser micro-structured platinum thin films by pulsed-DC reactive sputtering of iridium metal in oxygen-containing atmosphere, to obtain high charge capacity coatings for neural stimulation applications. The micro-structuring of platinum films was achieved by a pulsed-laser-based technique (KrF excimer laser emitting at lambda=248nm). The surface morphology of the micro-structured films was studied using different surface characterization techniques. In-vitro biocompatibility of these laser micro-structured films coated with iridium oxide thin films was evaluated using cortical neurons isolated from rat embryo brain. Characterization of these laser micro-structured films coated with iridium oxide, by cyclic voltammetry and impedance spectroscopy has revealed a considerable decrease in impedance and increase in charge capacity. A comparison between amorphous and crystalline iridium oxide thin films as electrode materials indicated that amorphous iridium oxide has significantly higher charge capacity and lower impedance making it preferable material for neural stimulation application. Our biocompatibility studies show that neural cells can grow and differentiate successfully on our laser micro-structured films coated with iridium oxide. This indicates that reactively sputtered iridium oxide (SIROF) is biocompatible.

Automatic M1-SO Montage Headgear for Transcranial Direct Current Stimulation (TDCS) Suitable for Home and High-Throughput In-Clinic Applications.

PubMed

Knotkova, Helena; Riggs, Alexa; Berisha, Destiny; Borges, Helen; Bernstein, Henry; Patel, Vaishali; Truong, Dennis Q; Unal, Gozde; Arce, Denis; Datta, Abhishek; Bikson, Marom

2018-05-15

Non-invasive transcranial direct current stimulation (tDCS) over the motor cortex is broadly investigated to modulate functional outcomes such as motor function, sleep characteristics, or pain. The most common montages that use two large electrodes (25-35 cm 2 ) placed over the area of motor cortex and contralateral supraorbital region (M1-SO montages) require precise measurements, usually using the 10-20 EEG system, which is cumbersome in clinics and not suitable for applications by patients at home. The objective was to develop and test novel headgear allowing for reproduction of the M1-SO montage without the 10-20 EEG measurements, neuronavigation, or TMS. Points C3/C4 of the 10-20 EEG system is the conventional reference for the M1 electrode. The headgear was designed using an orthogonal, fixed-angle approach for connection of frontal and coronal headgear components. The headgear prototype was evaluated for accuracy and replicability of the M1 electrode position in 600 repeated measurements compared to manually determined C3 in 30 volunteers. Computational modeling was used to estimate brain current flow at the mean and maximum recorded electrode placement deviations from C3. The headgear includes navigational points for accurate placement and assemblies to hold electrodes in the M1-SO position without measurement by the user. Repeated measurements indicated accuracy and replicability of the electrode position: the mean [SD] deviation of the M1 electrode (size 5 × 5 cm) from C3 was 1.57 [1.51] mm, median 1 mm. Computational modeling suggests that the potential deviation from C3 does not produce a significant change in brain current flow. The novel approach to M1-SO montage using a fixed-angle headgear not requiring measurements by patients or caregivers facilitates tDCS studies in home settings and can replace cumbersome C3 measurements for clinical tDCS applications. © 2018 International Neuromodulation Society.

Transcranial electrical stimulation over visual cortex evokes phosphenes with a retinal origin.

PubMed

Kar, Kohitij; Krekelberg, Bart

2012-10-01

Transcranial electrical stimulation (tES) is a promising therapeutic tool for a range of neurological diseases. Understanding how the small currents used in tES spread across the scalp and penetrate the brain will be important for the rational design of tES therapies. Alternating currents applied transcranially above visual cortex induce the perception of flashes of light (phosphenes). This makes the visual system a useful model to study tES. One hypothesis is that tES generates phosphenes by direct stimulation of the cortex underneath the transcranial electrode. Here, we provide evidence for the alternative hypothesis that phosphenes are generated in the retina by current spread from the occipital electrode. Building on the existing literature, we first confirm that phosphenes are induced at lower currents when electrodes are placed farther away from visual cortex and closer to the eye. Second, we explain the temporal frequency tuning of phosphenes based on the well-known response properties of primate retinal ganglion cells. Third, we show that there is no difference in the time it takes to evoke phosphenes in the retina or by stimulation above visual cortex. Together, these findings suggest that phosphenes induced by tES over visual cortex originate in the retina. From this, we infer that tES currents spread well beyond the area of stimulation and are unlikely to lead to focal neural activation. Novel stimulation protocols that optimize current distributions are needed to overcome these limitations of tES.

Intravascular Neural Interface with Nanowire Electrode

PubMed Central

Watanabe, Hirobumi; Takahashi, Hirokazu; Nakao, Masayuki; Walton, Kerry; Llinás, Rodolfo R.

2010-01-01

Summary A minimally invasive electrical recording and stimulating technique capable of simultaneously monitoring the activity of a significant number (e.g., 103 to 104) of neurons is an absolute prerequisite in developing an effective brain–machine interface. Although there are many excellent methodologies for recording single or multiple neurons, there has been no methodology for accessing large numbers of cells in a behaving experimental animal or human individual. Brain vascular parenchyma is a promising candidate for addressing this problem. It has been proposed [1, 2] that a multitude of nanowire electrodes introduced into the central nervous system through the vascular system to address any brain area may be a possible solution. In this study we implement a design for such microcatheter for ex vivo experiments. Using Wollaston platinum wire, we design a submicron-scale electrode and develop a fabrication method. We then evaluate the mechanical properties of the electrode in a flow when passing through the intricacies of the capillary bed in ex vivo Xenopus laevis experiments. Furthermore, we demonstrate the feasibility of intravascular recording in the spinal cord of Xenopus laevis. PMID:21572940

Modulation and detection of single neuron activity using spin transfer nano-oscillators

NASA Astrophysics Data System (ADS)

Algarin, Jose Miguel; Ramaswamy, Bharath; Venuti, Lucy; Swierzbinski, Matthew; Villar, Pablo; Chen, Yu-Jin; Krivorotov, Ilya; Weinberg, Irving N.; Herberholz, Jens; Araneda, Ricardo; Shapiro, Benjamin; Waks, Edo

2017-09-01

The brain is a complex network of interconnected circuits that exchange electrical signals with each other. These electrical signals provide insight on how neural circuits code information, and give rise to sensations, thoughts, emotions and actions. Currents methods to detect and modulate these electrical signals use implanted electrodes or optical fields with light sensitive dyes in the brain. These techniques require complex surgeries or suffer low resolution. In this talk we explore a new method to both image and stimulate single neurons using spintronics. We propose using a Spin Transfer Nano-Oscillators (STNOs) as a nanoscale sensor that converts neuronal action potentials to microwave field oscillations that can be detected wirelessly by magnetic induction. We will describe our recent proof-of-concept demonstration of both detection and wireless modulation of neuronal activity using STNOs. For detection we use electrodes to connect a STNO to a lateral giant crayfish neuron. When we stimulate the neuron, the STNO responds to the neuronal activity with a corresponding microwave signal. For modulation, we stimulate the STNOs wirelessly using an inductively coupled solenoid. The STNO rectifies the induced microwave signal to produce a direct voltage. This direct voltage from the STNO, when applied in the vicinity of a mammalian neuron, changes the frequency of electrical signals produced by the neuron.

Diffusion Tensor Imaging Based Thalamic Segmentation in Deep Brain Stimulation for Chronic Pain Conditions

PubMed Central

Kim, Won; Chivukula, Srinivas; Hauptman, Jason; Pouratian, Nader

2016-01-01

Background/Aims Thalamic deep brain stimulation (DBS) for the treatment of medically refractory pain has largely been abandoned on account of its inconsistent and oftentimes poor efficacy. Our aim here was to use diffusion tensor imaging (DTI)-based segmentation to assess the internal thalamic nuclei of patients who have undergone thalamic DBS for intractable pain and retrospectively correlate lead position with clinical outcome. Methods DTI-based segmentation was performed on 5 patients who underwent sensory thalamus DBS for chronic pain. Postoperative computed tomography (CT) images obtained for electrode placement were fused with preoperative MRIs that had undergone DTI-based thalamic segmentation. Sensory thalamus maps of 4 patients were analyzed for lead positioning and interpatient variability. Results Four patients who experienced significant pain relief following DBS demonstrated contact positions within the DTI-determined sensory thalamus or in its vicinity, whereas one who did not respond to stimulation did not. Only four voxels (2%) within the sensory thalamus were mutually shared among patients; 108 voxels (58%) were uniquely represented. Conclusions DTI-based segmentation of the thalamus can be used to confirm thalamic lead placement relative to the sensory thalamus, and may serve as a useful tool to guide thalamic DBS electrode implantation in the future. PMID:27537848

Adverse events associated with deep brain stimulation for movement disorders: analysis of 510 consecutive cases.

PubMed

Patel, Daxa M; Walker, Harrison C; Brooks, Rebekah; Omar, Nidal; Ditty, Benjamin; Guthrie, Barton L

2015-03-01

Although numerous studies have focused on the efficacy of deep brain stimulation (DBS) for movement disorders, less is known about surgical adverse events, especially over longer time intervals. Here, we analyze adverse events in 510 consecutive cases from a tertiary movement disorders center at up to 10 years postoperatively. We conducted a retrospective review of adverse events from craniotomies between January 2003 and March 2013. The adverse events were categorized into 2 broad categories--immediate perioperative and time-dependent postoperative events. Across all targets, perioperative mental status change occurred in 18 (3.5%) cases, and symptomatic intracranial hemorrhage occurred in 4 (0.78%) cases. The most common hardware-related event was skin erosion in 13 (2.5%) cases. The most frequent stimulation-related event was speech disturbance in 16 (3.1%) cases. There were no significant differences among surgical targets with respect to the incidence of these events. Time-dependent postoperative events leading to the revision of a given DBS electrode for any reason occurred in 4.7% ± 1.0%, 9.3% ± 1.4%, and 12.4% ± 1.5% of electrodes at 1, 4, and 7 years postoperatively, respectively. Staged bilateral DBS was associated with approximately twice the risk of repeat surgery for electrode replacement vs unilateral surgery (P = .020). These data provide low incidences for adverse events in a large series of DBS surgeries for movement disorders at up to 10 years follow-up. Accurate estimates of adverse events will better inform patients and caregivers about the potential risks and benefits of surgery and provide normative data for process improvement.

Low-frequency stimulation of the external globus palladium produces anti-epileptogenic and anti-ictogenic actions in rats.

PubMed

Cheng, Hui; Kuang, Yi-fang; Liu, Yang; Wang, Yi; Xu, Zheng-hao; Gao, Feng; Zhang, Shi-hong; Ding, Mei-ping; Chen, Zhong

2015-08-01

To investigate the anti-epileptic effects of deep brain stimulation targeting the external globus palladium (GPe) in rats. For inducing amygdala kindling and deep brain stimulation, bipolar stainless-steel electrodes were implanted in SD rats into right basolateral amygdala and right GPe, respectively. The effects of deep brain stimulation were evaluated in the amygdala kindling model, maximal electroshock model (MES) and pentylenetetrazole (PTZ) model. Moreover, the background EEGs in the amygdala and GPe were recorded. Low-frequency stimulation (0.1 ms, 1 Hz, 15 min) at the GPe slowed the progression of seizure stages and shortened the after-discharge duration (ADD) during kindling acquisition. Furthermore, low-frequency stimulation significantly decreased the incidence of generalized seizures, suppressed the average stage, and shortened the cumulative ADD and generalized seizure duration in fully kindled rats. In addition, low-frequency stimulation significantly suppressed the average stage of MES-induced seizures and increased the latency to generalized seizures in the PTZ model. High-frequency stimulation (0.1 ms, 130 Hz, 5 min) at the GPe had no anti-epileptic effect and even aggravated epileptogenesis induced by amygdala kindling. EEG analysis showed that low-frequency stimulation at the GPe reversed the increase in delta power, whereas high-frequency stimulation at the GPe had no such effect. Low-frequency stimulation, but not high-frequency stimulation, at the GPe exerts therapeutic effect on temporal lobe epilepsy and tonic-colonic generalized seizures, which may be due to interference with delta rhythms. The results suggest that modulation of GPe activity using low-frequency stimulation or drugs may be a promising epilepsy treatment.

Potential predictors for the amount of intra-operative brain shift during deep brain stimulation surgery

NASA Astrophysics Data System (ADS)

Datteri, Ryan; Pallavaram, Srivatsan; Konrad, Peter E.; Neimat, Joseph S.; D'Haese, Pierre-François; Dawant, Benoit M.

2011-03-01

A number of groups have reported on the occurrence of intra-operative brain shift during deep brain stimulation (DBS) surgery. This has a number of implications for the procedure including an increased chance of intra-cranial bleeding and complications due to the need for more exploratory electrodes to account for the brain shift. It has been reported that the amount of pneumocephalus or air invasion into the cranial cavity due to the opening of the dura correlates with intraoperative brain shift. Therefore, pre-operatively predicting the amount of pneumocephalus expected during surgery is of interest toward accounting for brain shift. In this study, we used 64 DBS patients who received bilateral electrode implantations and had a post-operative CT scan acquired immediately after surgery (CT-PI). For each patient, the volumes of the pneumocephalus, left ventricle, right ventricle, third ventricle, white matter, grey matter, and cerebral spinal fluid were calculated. The pneumocephalus was calculated from the CT-PI utilizing a region growing technique that was initialized with an atlas-based image registration method. A multi-atlas-based image segmentation method was used to segment out the ventricles of each patient. The Statistical Parametric Mapping (SPM) software package was utilized to calculate the volumes of the cerebral spinal fluid (CSF), white matter and grey matter. The volume of individual structures had a moderate correlation with pneumocephalus. Utilizing a multi-linear regression between the volume of the pneumocephalus and the statistically relevant individual structures a Pearson's coefficient of r = 0.4123 (p = 0.0103) was found. This study shows preliminary results that could be used to develop a method to predict the amount of pneumocephalus ahead of the surgery.

tDCS polarity effects in motor and cognitive domains: a meta-analytical review.

PubMed

Jacobson, Liron; Koslowsky, Meni; Lavidor, Michal

2012-01-01

In vivo effects of transcranial direct current stimulation (tDCS) have attracted much attention nowadays as this area of research spreads to both the motor and cognitive domains. The common assumption is that the anode electrode causes an enhancement of cortical excitability during stimulation, which then lasts for a few minutes thereafter, while the cathode electrode generates the opposite effect, i.e., anodal-excitation and cathodal-inhibition effects (AeCi). Yet, this dual-polarity effect has not been observed in all tDCS studies. Here, we conducted a meta-analytical review aimed to investigate the homogeneity/heterogeneity of the effect sizes of the AeCi dichotomy in both motor and cognitive functions. The AeCi effect was found to occur quite commonly with motor investigations and rarely in cognitive studies. When the anode electrode is applied over a non-motor area, in most cases, it will cause an excitation as measured by a relevant cognitive or perceptual task; however, the cathode electrode rarely causes an inhibition. We found homogeneity in motor studies and heterogeneity in cognitive studies with the electrode's polarity serving as a moderator that can explain the source of heterogeneity in cognitive studies. The lack of inhibitory cathodal effects might reflect compensation processes as cognitive functions are typically supported by rich brain networks. Further insights as to the polarity and domain interaction are offered, including subdivision to different classes of cognitive functions according to their likelihood of being affected by stimulation.

Measurements of RF heating during 3.0-T MRI of a pig implanted with deep brain stimulator.

PubMed

Gorny, Krzysztof R; Presti, Michael F; Goerss, Stephan J; Hwang, Sun C; Jang, Dong-Pyo; Kim, Inyong; Min, Hoon-Ki; Shu, Yunhong; Favazza, Christopher P; Lee, Kendall H; Bernstein, Matt A

2013-06-01

To present preliminary, in vivo temperature measurements during MRI of a pig implanted with a deep brain stimulation (DBS) system. DBS system (Medtronic Inc., Minneapolis, MN) was implanted in the brain of an anesthetized pig. 3.0-T MRI was performed with a T/R head coil using the low-SAR GRE EPI and IR-prepped GRE sequences (SAR: 0.42 and 0.39 W/kg, respectively), and the high-SAR 4-echo RF spin echo (SAR: 2.9 W/kg). Fluoroptic thermometry was used to directly measure RF-related heating at the DBS electrodes, and at the implantable pulse generator (IPG). For reference the measurements were repeated in the same pig at 1.5 T and, at both field strengths, in a phantom. At 3.0T, the maximal temperature elevations at DBS electrodes were 0.46 °C and 2.3 °C, for the low- and high-SAR sequences, respectively. No heating was observed on the implanted IPG during any of the measurements. Measurements of in vivo heating differed from those obtained in the phantom. The 3.0-T MRI using GRE EPI and IR-prepped GRE sequences resulted in local temperature elevations at DBS electrodes of no more than 0.46 °C. Although no extrapolation should be made to human exams and much further study will be needed, these preliminary data are encouraging for the future use 3.0-T MRI in patients with DBS. Copyright © 2013 Elsevier Inc. All rights reserved.

A Computerized Microelectrode Recording to Magnetic Resonance Imaging Mapping System for Subthalamic Nucleus Deep Brain Stimulation Surgery.

PubMed

Dodani, Sunjay S; Lu, Charles W; Aldridge, J Wayne; Chou, Kelvin L; Patil, Parag G

2018-06-01

Accurate electrode placement is critical to the success of deep brain stimulation (DBS) surgery. Suboptimal targeting may arise from poor initial target localization, frame-based targeting error, or intraoperative brain shift. These uncertainties can make DBS surgery challenging. To develop a computerized system to guide subthalamic nucleus (STN) DBS electrode localization and to estimate the trajectory of intraoperative microelectrode recording (MER) on magnetic resonance (MR) images algorithmically during DBS surgery. Our method is based upon the relationship between the high-frequency band (HFB; 500-2000 Hz) signal from MER and voxel intensity on MR images. The HFB profile along an MER trajectory recorded during surgery is compared to voxel intensity profiles along many potential trajectories in the region of the surgically planned trajectory. From these comparisons of HFB recordings and potential trajectories, an estimate of the MER trajectory is calculated. This calculated trajectory is then compared to actual trajectory, as estimated by postoperative high-resolution computed tomography. We compared 20 planned, calculated, and actual trajectories in 13 patients who underwent STN DBS surgery. Targeting errors for our calculated trajectories (2.33 mm ± 0.2 mm) were significantly less than errors for surgically planned trajectories (2.83 mm ± 0.2 mm; P = .01), improving targeting prediction in 70% of individual cases (14/20). Moreover, in 4 of 4 initial MER trajectories that missed the STN, our method correctly indicated the required direction of targeting adjustment for the DBS lead to intersect the STN. A computer-based algorithm simultaneously utilizing MER and MR information potentially eases electrode localization during STN DBS surgery.

Measurements of RF Heating during 3.0T MRI of a Pig Implanted with Deep Brain Stimulator

PubMed Central

Gorny, Krzysztof R; Presti, Michael F; Goerss, Stephan J; Hwang, Sun C; Jang, Dong-Pyo; Kim, Inyong; Shu, Yunhong; Favazza, Christopher P; Lee, Kendall H; Bernstein, Matt A

2012-01-01

Purpose To present preliminary, in vivo temperature measurements during MRI of a pig implanted with a deep brain stimulation (DBS) system. Materials and Methods DBS system (Medtronic Inc., Minneapolis, MN) was implanted in the brain of an anesthetized pig. 3.0T MRI was performed with a T/R head coil using the low-SAR GRE EPI and IR-prepped GRE sequences (SAR: 0.42 W/kg and 0.39 W/kg, respectively), and the high-SAR 4-echo RF spin echo (SAR: 2.9 W/kg). Fluoroptic thermometry was used to directly measure RF-related heating at the DBS electrodes, and at the implantable pulse generator (IPG). For reference the measurements were repeated in the same pig at 1.5T and, at both field strengths, in a phantom. Results At 3.0T, the maximal temperature elevations at DBS electrodes were 0.46 °C and 2.3 °C, for the low- and high-SAR sequences, respectively. No heating was observed on the implanted IPG during any of the measurements. Measurements of in-vivo heating differed from those obtained in the phantom. Conclusion The 3.0T MRI using GRE EPI and IR-prepped GRE sequences resulted in local temperature elevations at DBS electrodes of no more than 0.46°C. Although no extrapolation should be made to human exams and much further study will be needed, these preliminary data are encouraging for the future use 3.0T MRI in patients with DBS. PMID:23228310

Functional Magnetic Resonance Imaging Networks Induced by Intracranial Stimulation May Help Defining the Epileptogenic Zone

PubMed Central

Zhang, Myron; Avitsian, Rafi; Bhattacharyya, Pallab; Bulacio, Juan; Cendes, Fernando; Enatsu, Rei; Lowe, Mark; Najm, Imad; Nair, Dileep; Phillips, Michael; Gonzalez-Martinez, Jorge

2014-01-01

Abstract Patients with medically intractable epilepsy often undergo invasive evaluation and surgery, with a 50% success rate. The low success rate is likely due to poor identification of the epileptogenic zone (EZ), the brain area causing seizures. This work introduces a new method using functional magnetic resonance imaging (fMRI) with simultaneous direct electrical stimulation of the brain that could help localize the EZ, performed in five patients with medically intractable epilepsy undergoing invasive evaluation with intracranial depth electrodes. Stimulation occurred in a location near the hypothesized EZ and a location away. Electrical recordings in response to stimulation were recorded and compared to fMRI. Multiple stimulation parameters were varied, like current and frequency. The brain areas showing fMRI response were compared with the areas resected and the success of surgery. Robust fMRI maps of activation networks were easily produced, which also showed a significant but weak positive correlation between quantitative measures of blood-oxygen-level-dependent (BOLD) activity and measures of electrical activity in response to direct electrical stimulation (mean correlation coefficient of 0.38 for all acquisitions that produced a strong BOLD response). For four patients with outcome data at 6 months, successful surgical outcome is consistent with the resection of brain areas containing high local fMRI activity. In conclusion, this method demonstrates the feasibility of simultaneous direct electrical stimulation and fMRI in humans, which allows the study of brain connectivity with high resolution and full spatial coverage. This innovative technique could be used to better define the localization and extension of the EZ in intractable epilepsies, as well as for other functional neurosurgical procedures. PMID:24735069

Induction of Fear by Intraoperative Stimulation During Awake Craniotomy: Case Presentation and Systematic Review of the Literature.

PubMed

Nowacki, Andreas; Seidel, Kathleen; Schucht, Philippe; Schindler, Kaspar; Abela, Eugenio; Heinemann, Dorothea; Gutbrod, Klemens; Wiest, Roland; Raabe, Andreas; Pollo, Claudio

2015-08-01

A case is presented and a systematic review of the literature is provided to update our current knowledge of induction of fear by cortical stimulation. We present a case of refractory epilepsy associated with a lesion where fear could be induced by intraoperative electrical stimulation of the posterior inner part of the superior temporal gyrus. We performed a systematic review of the literature using PubMed with the key words "epilepsy AND emotion", "cortical stimulation AND emotion," and "human brain stimulation AND behavior". Intraoperative cortical stimulation of the inner part of the posterior superior temporal gyrus reliably induced fear and progressive screaming behavior. Stimulation through subdural grid electrodes did not induce this phenomenon. A systematic review of the literature identified fear induction by stimulation of different widespread cortical areas including the temporal pole, the insula, and the anterior cingulate cortex. The posterior part of the superior temporal gyrus has so far not been associated with fear induction after electrical stimulation. Although our observation suggests that this area of the brain could be part of a network involved in the elicitation of fear, dysfunction of this network induced by epilepsy could also explain the observed phenomenon. Electrophysiologic and imaging studies must be conducted to improve our understanding of the cortical networks forming the neuroanatomical substrate of higher brain functions and experiences such as fear. Copyright © 2015 Elsevier Inc. All rights reserved.

Analysis of evoked deep brain connectivity.

PubMed

Klimeš, Petr; Janeček, Jiři; Jurák, Pavel; Halámek, Josef; Chládek, Han; Brázdil, Milan

2013-01-01

Establishing dependencies and connectivity among different structures in the human brain is an extremely complex issue. Methods that are often used for connectivity analysis are based on correlation mechanisms. Correlation methods can analyze changes in signal shape or instantaneous power level. Although recent studies imply that observation of results from both groups of methods together can disclose some of the basic functions and behavior of the human brain during mental activity and decision-making, there is no technique covering changes in the shape of signals along with changes in their power levels. We present a method using a time evaluation of the correlation along with a comparison of power levels in every available contact pair from intracranial electrodes placed in deep brain structures. Observing shape changes in signals after stimulation together with their power levels provides us with new information about signal character between different structures in the brain during task-related events - visual stimulation with motor response. The results for a subject with 95 intracerebral contacts used in this paper demonstrate a clear methodology capable of spatially analyzing connectivity among deep brain structures.

Age-dependent effects of brain stimulation on network centrality.

PubMed

Antonenko, Daria; Nierhaus, Till; Meinzer, Marcus; Prehn, Kristin; Thielscher, Axel; Ittermann, Bernd; Flöel, Agnes

2018-04-18

Functional magnetic resonance imaging (fMRI) studies have suggested that advanced age may mediate the effects of transcranial direct current stimulation (tDCS) on brain function. However, studies directly comparing neural tDCS effects between young and older adults are scarce and limited to task-related imaging paradigms. Resting-state (rs-) fMRI, that is independent of age-related differences in performance, is well suited to investigate age-associated differential neural tDCS effects. Three "online" tDCS conditions (anodal, cathodal, sham) were compared in a cross-over, within-subject design, in 30 young and 30 older adults. Active stimulation targeted the left sensorimotor network (active electrode over left sensorimotor cortex with right supraorbital reference electrode). A graph-based rs-fMRI data analysis approach (eigenvector centrality mapping) and complementary seed-based analyses characterized neural tDCS effects. An interaction between anodal tDCS and age group was observed. Specifically, centrality in bilateral paracentral and posterior regions (precuneus, superior parietal cortex) was increased in young, but decreased in older adults. Seed-based analyses revealed that these opposing patterns of tDCS-induced centrality modulation originated from differential effects of tDCS on functional coupling of the stimulated left paracentral lobule. Cathodal tDCS did not show significant effects. Our study provides first evidence for differential tDCS effects on neural network organization in young and older adults. Anodal stimulation mainly affected coupling of sensorimotor with ventromedial prefrontal areas in young and decoupling with posteromedial areas in older adults. Copyright © 2018 Elsevier Inc. All rights reserved.

Computational modeling of pedunculopontine nucleus deep brain stimulation

NASA Astrophysics Data System (ADS)

Zitella, Laura M.; Mohsenian, Kevin; Pahwa, Mrinal; Gloeckner, Cory; Johnson, Matthew D.

2013-08-01

Objective. Deep brain stimulation (DBS) near the pedunculopontine nucleus (PPN) has been posited to improve medication-intractable gait and balance problems in patients with Parkinson's disease. However, clinical studies evaluating this DBS target have not demonstrated consistent therapeutic effects, with several studies reporting the emergence of paresthesia and oculomotor side effects. The spatial and pathway-specific extent to which brainstem regions are modulated during PPN-DBS is not well understood. Approach. Here, we describe two computational models that estimate the direct effects of DBS in the PPN region for human and translational non-human primate (NHP) studies. The three-dimensional models were constructed from segmented histological images from each species, multi-compartment neuron models and inhomogeneous finite element models of the voltage distribution in the brainstem during DBS. Main Results. The computational models predicted that: (1) the majority of PPN neurons are activated with -3 V monopolar cathodic stimulation; (2) surgical targeting errors of as little as 1 mm in both species decrement activation selectivity; (3) specifically, monopolar stimulation in caudal, medial, or anterior PPN activates a significant proportion of the superior cerebellar peduncle (up to 60% in the human model and 90% in the NHP model at -3 V) (4) monopolar stimulation in rostral, lateral or anterior PPN activates a large percentage of medial lemniscus fibers (up to 33% in the human model and 40% in the NHP model at -3 V) and (5) the current clinical cylindrical electrode design is suboptimal for isolating the modulatory effects to PPN neurons. Significance. We show that a DBS lead design with radially-segmented electrodes may yield improved functional outcome for PPN-DBS.

Comparison of the shock artifacts induced by tripolar and bipolar electrical stimulation techniques.

PubMed

Wee, A S; Jiles, K; Brennan, R

2001-01-01

Tripolar and bipolar electrical stimulation procedures were performed on the upper limbs of eight subjects. The mid-forearm was stimulated electrically (tripolar or bipolar) by surface electrodes, and the induced stimulus shock artifacts were recorded simultaneously from the wrist and elbow. During tripolar stimulation, two types of stimulating configurations were utilized: with the center electrode designated as the cathode and the two outermost electrodes connected to a common anode, and vice versa. During bipolar stimulation, the center electrode served as one pole of the stimulator, and one of the two outermost electrodes of the tripolar stimulator was disconnected. The stimulus intensity was kept constant in all stimulating procedures. Artifacts were reduced significantly during tripolar compared to bipolar stimulation, if the outermost electrodes of the tripolar stimulator (which were facing the recording electrodes) were also oriented toward the recording sites during bipolar stimulation and had the same stimulus polarity. Artifacts were slightly reduced in amplitude from tripolar stimulation, if the center electrode were oriented toward the recording sites during bipolar stimulation and had the same stimulus polarity as previously used during tripolar stimulation.

Electrical bioimpedance enabling prompt intervention in traumatic brain injury

NASA Astrophysics Data System (ADS)

Seoane, Fernando; Atefi, S. Reza

2017-05-01

Electrical Bioimpedance (EBI) is a well spread technology used in clinical practice across the world. Advancements in Textile material technology with conductive textile fabrics and textile-electronics integration have allowed exploring potential applications for Wearable Measurement Sensors and Systems exploiting. The sensing principle of electrical bioimpedance is based on the intrinsic passive dielectric properties of biological tissue. Using a pair of electrodes, tissue is electrically stimulated and the electrical response can be sensed with another pair of surface electrodes. EBI spectroscopy application for cerebral monitoring of neurological conditions such as stroke and perinatal asphyxia in newborns have been justified using animal studies and computational simulations. Such studies have shown proof of principle that neurological pathologies indeed modify the dielectric composition of the brain that is detectable via EBI. Similar to stroke, Traumatic Brain Injury (TBI) also affects the dielectric properties of brain tissue that can be detected via EBI measurements. Considering the portable and noninvasive characteristics of EBI it is potentially useful for prehospital triage of TBI patients where. In the battlefield blast induced Traumatic Brain Injuries are very common. Brain damage must be assessed promptly to have a chance to prevent severe damage or eventually death. The relatively low-complexity of the sensing hardware required for EBI sensing and the already proven compatibility with textile electrodes suggest the EBI technology is indeed a candidate for developing a handheld device equipped with a sensorized textile cap to produce an examination in minutes for enabling medically-guided prompt intervention.

Fiber-array based optogenetic prosthetic system for stimulation therapy

NASA Astrophysics Data System (ADS)

Gu, Ling; Cote, Chris; Tejeda, Hector; Mohanty, Samarendra

2012-02-01

Recent advent of optogenetics has enabled activation of genetically-targeted neuronal cells using low intensity blue light with high temporal precision. Since blue light is attenuated rapidly due to scattering and absorption in neural tissue, optogenetic treatment of neurological disorders may require stimulation of specific cell types in multiple regions of the brain. Further, restoration of certain neural functions (vision, and auditory etc) requires accurate spatio-temporal stimulation patterns rather than just precise temporal stimulation. In order to activate multiple regions of the central nervous system in 3D, here, we report development of an optogenetic prosthetic comprising of array of fibers coupled to independently-controllable LEDs. This design avoids direct contact of LEDs with the brain tissue and thus does not require electrical and heat isolation, which can non-specifically stimulate and damage the local brain regions. The intensity, frequency, and duty cycle of light pulses from each fiber in the array was controlled independently using an inhouse developed LabView based program interfaced with a microcontroller driving the individual LEDs. While the temporal profile of the light pulses was controlled by varying the current driving the LED, the beam profile emanating from each fiber tip could be sculpted by microfabrication of the fiber tip. The fiber array was used to stimulate neurons, expressing channelrhodopsin-2, in different locations within the brain or retina. Control of neural activity in the mice cortex, using the fiber-array based prosthetic, is evaluated from recordings made with multi-electrode array (MEA). We also report construction of a μLED array based prosthetic for spatio-temporal stimulation of cortex.

Neurophysiological Changes Measured Using Somatosensory Evoked Potentials.

PubMed

Macerollo, Antonella; Brown, Matt J N; Kilner, James M; Chen, Robert

2018-05-01

Measurements of somatosensory evoked potentials (SEPs), recorded using electroencephalography during different phases of movement, have been fundamental in understanding the neurophysiological changes related to motor control. SEP recordings have also been used to investigate adaptive plasticity changes in somatosensory processing related to active and observational motor learning tasks. Combining noninvasive brain stimulation with SEP recordings and intracranial SEP depth recordings, including recordings from deep brain stimulation electrodes, has been critical in identifying neural areas involved in specific temporal stages of somatosensory processing. Consequently, this fundamental information has furthered our understanding of the maladaptive plasticity changes related to pathophysiology of diseases characterized by abnormal movements, such as Parkinson's disease, dystonia, and functional movement disorders. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Reducing interaction in simultaneous paired stimulation with CI.

PubMed

Vellinga, Dirk; Bruijn, Saskia; Briaire, Jeroen J; Kalkman, Randy K; Frijns, Johan H M

2017-01-01

In this study simultaneous paired stimulation of electrodes in cochlear implants is investigated by psychophysical experiments in 8 post-lingually deaf subjects (and one extra subject who only participated in part of the experiments). Simultaneous and sequential monopolar stimulation modes are used as references and are compared to channel interaction compensation, partial tripolar stimulation and a novel sequential stimulation strategy named phased array compensation. Psychophysical experiments are performed to investigate both the loudness integration during paired stimulation at the main electrodes as well as the interaction with the electrode contact located halfway between the stimulating pair. The study shows that simultaneous monopolar stimulation has more loudness integration on the main electrodes and more interaction in between the electrodes than sequential stimulation. Channel interaction compensation works to reduce the loudness integration at the main electrodes, but does not reduce the interaction in between the electrodes caused by paired stimulation. Partial tripolar stimulation uses much more current to reach the needed loudness, but shows the same interaction in between the electrodes as sequential monopolar stimulation. In phased array compensation we have used the individual impedance matrix of each subject to calculate the current needed on each electrode to exactly match the stimulation voltage along the array to that of sequential stimulation. The results show that the interaction in between the electrodes is the same as monopolar stimulation. The strategy uses less current than partial tripolar stimulation, but more than monopolar stimulation. In conclusion, the paper shows that paired stimulation is possible if the interaction is compensated.

Clinical Pilot Study and Computational Modeling of Bitemporal Transcranial Direct Current Stimulation, and Safety of Repeated Courses of Treatment, in Major Depression.

PubMed

Ho, Kerrie-Anne; Bai, Siwei; Martin, Donel; Alonzo, Angelo; Dokos, Socrates; Loo, Colleen K

2015-12-01

This study aimed to examine a bitemporal (BT) transcranial direct current stimulation (tDCS) electrode montage for the treatment of depression through a clinical pilot study and computational modeling. The safety of repeated courses of stimulation was also examined. Four participants with depression who had previously received multiple courses of tDCS received a 4-week course of BT tDCS. Mood and neuropsychological function were assessed. The results were compared with previous courses of tDCS given to the same participants using different electrode montages. Computational modeling examined the electric field maps produced by the different montages. Three participants showed clinical improvement with BT tDCS (mean [SD] improvement, 49.6% [33.7%]). There were no adverse neuropsychological effects. Computational modeling showed that the BT montage activates the anterior cingulate cortices and brainstem, which are deep brain regions that are important for depression. However, a fronto-extracephalic montage stimulated these areas more effectively. No adverse effects were found in participants receiving up to 6 courses of tDCS. Bitemporal tDCS was safe and led to clinically meaningful efficacy in 3 of 4 participants. However, computational modeling suggests that the BT montage may not activate key brain regions in depression more effectively than another novel montage--fronto-extracephalic tDCS. There is also preliminary evidence to support the safety of up to 6 repeated courses of tDCS.

Modulation of Total Sleep Time by Transcranial Direct Current Stimulation (tDCS).

PubMed

Frase, Lukas; Piosczyk, Hannah; Zittel, Sulamith; Jahn, Friederike; Selhausen, Peter; Krone, Lukas; Feige, Bernd; Mainberger, Florian; Maier, Jonathan G; Kuhn, Marion; Klöppel, Stefan; Normann, Claus; Sterr, Annette; Spiegelhalder, Kai; Riemann, Dieter; Nitsche, Michael A; Nissen, Christoph

2016-09-01

Arousal and sleep are fundamental physiological processes, and their modulation is of high clinical significance. This study tested the hypothesis that total sleep time (TST) in humans can be modulated by the non-invasive brain stimulation technique transcranial direct current stimulation (tDCS) targeting a 'top-down' cortico-thalamic pathway of sleep-wake regulation. Nineteen healthy participants underwent a within-subject, repeated-measures protocol across five nights in the sleep laboratory with polysomnographic monitoring (adaptation, baseline, three experimental nights). tDCS was delivered via bi-frontal target electrodes and bi-parietal return electrodes before sleep (anodal 'activation', cathodal 'deactivation', and sham stimulation). Bi-frontal anodal stimulation significantly decreased TST, compared with cathodal and sham stimulation. This effect was location specific. Bi-frontal cathodal stimulation did not significantly increase TST, potentially due to ceiling effects in good sleepers. Exploratory resting-state EEG analyses before and after the tDCS protocols were consistent with the notion of increased cortical arousal after anodal stimulation and decreased cortical arousal after cathodal stimulation. The study provides proof-of-concept that TST can be decreased by non-invasive bi-frontal anodal tDCS in healthy humans. Further elucidating the 'top-down' pathway of sleep-wake regulation is expected to increase knowledge on the fundamentals of sleep-wake regulation and to contribute to the development of novel treatments for clinical conditions of disturbed arousal and sleep.

Modulation of Total Sleep Time by Transcranial Direct Current Stimulation (tDCS)

PubMed Central

Frase, Lukas; Piosczyk, Hannah; Zittel, Sulamith; Jahn, Friederike; Selhausen, Peter; Krone, Lukas; Feige, Bernd; Mainberger, Florian; Maier, Jonathan G; Kuhn, Marion; Klöppel, Stefan; Normann, Claus; Sterr, Annette; Spiegelhalder, Kai; Riemann, Dieter; Nitsche, Michael A; Nissen, Christoph

2016-01-01

Arousal and sleep are fundamental physiological processes, and their modulation is of high clinical significance. This study tested the hypothesis that total sleep time (TST) in humans can be modulated by the non-invasive brain stimulation technique transcranial direct current stimulation (tDCS) targeting a ‘top-down' cortico-thalamic pathway of sleep-wake regulation. Nineteen healthy participants underwent a within-subject, repeated-measures protocol across five nights in the sleep laboratory with polysomnographic monitoring (adaptation, baseline, three experimental nights). tDCS was delivered via bi-frontal target electrodes and bi-parietal return electrodes before sleep (anodal ‘activation', cathodal ‘deactivation', and sham stimulation). Bi-frontal anodal stimulation significantly decreased TST, compared with cathodal and sham stimulation. This effect was location specific. Bi-frontal cathodal stimulation did not significantly increase TST, potentially due to ceiling effects in good sleepers. Exploratory resting-state EEG analyses before and after the tDCS protocols were consistent with the notion of increased cortical arousal after anodal stimulation and decreased cortical arousal after cathodal stimulation. The study provides proof-of-concept that TST can be decreased by non-invasive bi-frontal anodal tDCS in healthy humans. Further elucidating the ‘top-down' pathway of sleep-wake regulation is expected to increase knowledge on the fundamentals of sleep-wake regulation and to contribute to the development of novel treatments for clinical conditions of disturbed arousal and sleep. PMID:27143601

Post-task Effects on EEG Brain Activity Differ for Various Differential Learning and Contextual Interference Protocols

PubMed Central

Henz, Diana; John, Alexander; Merz, Christian; Schöllhorn, Wolfgang I.

2018-01-01

A large body of research has shown superior learning rates in variable practice compared to repetitive practice. More specifically, this has been demonstrated in the contextual interference (CI) and in the differential learning (DL) approach that are both representatives of variable practice. Behavioral studies have indicate different learning processes in CI and DL. Aim of the present study was to examine immediate post-task effects on electroencephalographic (EEG) brain activation patterns after CI and DL protocols that reveal underlying neural processes at the early stage of motor consolidation. Additionally, we tested two DL protocols (gradual DL, chaotic DL) to examine the effect of different degrees of stochastic fluctuations within the DL approach with a low degree of fluctuations in gradual DL and a high degree of fluctuations in chaotic DL. Twenty-two subjects performed badminton serves according to three variable practice protocols (CI, gradual DL, chaotic DL), and a repetitive learning protocol in a within-subjects design. Spontaneous EEG activity was measured before, and immediately after each 20-min practice session from 19 electrodes. Results showed distinguishable neural processes after CI, DL, and repetitive learning. Increases in EEG theta and alpha power were obtained in somatosensory regions (electrodes P3, P7, Pz, P4, P8) in both DL conditions compared to CI, and repetitive learning. Increases in theta and alpha activity in motor areas (electrodes C3, Cz, C4) were found after chaotic DL compared to gradual DL, and CI. Anterior areas (electrodes F3, F7, Fz, F4, F8) showed increased activity in the beta and gamma bands after CI. Alpha activity was increased in occipital areas (electrodes O1, O2) after repetitive learning. Post-task EEG brain activation patterns suggest that DL stimulates the somatosensory and motor system, and engages more regions of the cortex than repetitive learning due to a tighter stimulation of the motor and somatosensory system during DL practice. CI seems to activate specifically executively controlled processing in anterior brain areas. We discuss the obtained patterns of post-training EEG traces as evidence for different underlying neural processes in CI, DL, and repetitive learning at the early stage of motor learning. PMID:29445334

A Network Model of Local Field Potential Activity in Essential Tremor and the Impact of Deep Brain Stimulation

PubMed Central

Mace, Michael; Pavese, Nicola; Borisyuk, Roman; Bain, Peter

2017-01-01

Essential tremor (ET), a movement disorder characterised by an uncontrollable shaking of the affected body part, is often professed to be the most common movement disorder, affecting up to one percent of adults over 40 years of age. The precise cause of ET is unknown, however pathological oscillations of a network of a number of brain regions are implicated in leading to the disorder. Deep brain stimulation (DBS) is a clinical therapy used to alleviate the symptoms of a number of movement disorders. DBS involves the surgical implantation of electrodes into specific nuclei in the brain. For ET the targeted region is the ventralis intermedius (Vim) nucleus of the thalamus. Though DBS is effective for treating ET, the mechanism through which the therapeutic effect is obtained is not understood. To elucidate the mechanism underlying the pathological network activity and the effect of DBS on such activity, we take a computational modelling approach combined with electrophysiological data. The pathological brain activity was recorded intra-operatively via implanted DBS electrodes, whilst simultaneously recording muscle activity of the affected limbs. We modelled the network hypothesised to underlie ET using the Wilson-Cowan approach. The modelled network exhibited oscillatory behaviour within the tremor frequency range, as did our electrophysiological data. By applying a DBS-like input we suppressed these oscillations. This study shows that the dynamics of the ET network support oscillations at the tremor frequency and the application of a DBS-like input disrupts this activity, which could be one mechanism underlying the therapeutic benefit. PMID:28068428

Bilateral adaptive deep brain stimulation is effective in Parkinson's disease.

PubMed

Little, Simon; Beudel, Martijn; Zrinzo, Ludvic; Foltynie, Thomas; Limousin, Patricia; Hariz, Marwan; Neal, Spencer; Cheeran, Binith; Cagnan, Hayriye; Gratwicke, James; Aziz, Tipu Z; Pogosyan, Alex; Brown, Peter

2016-07-01

Adaptive deep brain stimulation (aDBS) uses feedback from brain signals to guide stimulation. A recent acute trial of unilateral aDBS showed that aDBS can lead to substantial improvements in contralateral hemibody Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and may be superior to conventional continuous DBS in Parkinson's disease (PD). We test whether potential benefits are retained with bilateral aDBS and in the face of concurrent medication. We applied bilateral aDBS in 4 patients with PD undergoing DBS of the subthalamic nucleus. aDBS was delivered bilaterally with independent triggering of stimulation according to the amplitude of β activity at the corresponding electrode. Mean stimulation voltage was 3.0±0.1 volts. Motor assessments consisted of double-blinded video-taped motor UPDRS scores that included both limb and axial features. UPDRS scores were 43% (p=0.04; Cohen's d=1.62) better with aDBS than without stimulation. Motor improvement with aDBS occurred despite an average time on stimulation (ToS) of only 45%. Levodopa was well tolerated during aDBS and led to further reductions in ToS. Bilateral aDBS can improve both axial and limb symptoms and can track the need for stimulation across drug states. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Comparison of imaging modalities and source-localization algorithms in locating the induced activity during deep brain stimulation of the STN.

PubMed

Mideksa, K G; Singh, A; Hoogenboom, N; Hellriegel, H; Krause, H; Schnitzler, A; Deuschl, G; Raethjen, J; Schmidt, G; Muthuraman, M

2016-08-01

One of the most commonly used therapy to treat patients with Parkinson's disease (PD) is deep brain stimulation (DBS) of the subthalamic nucleus (STN). Identifying the most optimal target area for the placement of the DBS electrodes have become one of the intensive research area. In this study, the first aim is to investigate the capabilities of different source-analysis techniques in detecting deep sources located at the sub-cortical level and validating it using the a-priori information about the location of the source, that is, the STN. Secondly, we aim at an investigation of whether EEG or MEG is best suited in mapping the DBS-induced brain activity. To do this, simultaneous EEG and MEG measurement were used to record the DBS-induced electromagnetic potentials and fields. The boundary-element method (BEM) have been used to solve the forward problem. The position of the DBS electrodes was then estimated using the dipole (moving, rotating, and fixed MUSIC), and current-density-reconstruction (CDR) (minimum-norm and sLORETA) approaches. The source-localization results from the dipole approaches demonstrated that the fixed MUSIC algorithm best localizes deep focal sources, whereas the moving dipole detects not only the region of interest but also neighboring regions that are affected by stimulating the STN. The results from the CDR approaches validated the capability of sLORETA in detecting the STN compared to minimum-norm. Moreover, the source-localization results using the EEG modality outperformed that of the MEG by locating the DBS-induced activity in the STN.

Cross-frequency coupling in deep brain structures upon processing the painful sensory inputs.

PubMed

Liu, C C; Chien, J H; Kim, J H; Chuang, Y F; Cheng, D T; Anderson, W S; Lenz, F A

2015-09-10

Cross-frequency coupling has been shown to be functionally significant in cortical information processing, potentially serving as a mechanism for integrating functionally relevant regions in the brain. In this study, we evaluate the hypothesis that pain-related gamma oscillatory responses are coupled with low-frequency oscillations in the frontal lobe, amygdala and hippocampus, areas known to have roles in pain processing. We delivered painful laser pulses to random locations on the dorsal hand of five patients with uncontrolled epilepsy requiring depth electrode implantation for seizure monitoring. Two blocks of 40 laser stimulations were delivered to each subject and the pain-intensity was controlled at five in a 0-10 scale by adjusting the energy level of the laser pulses. Local-field-potentials (LFPs) were recorded through bilaterally implanted depth electrode contacts to study the oscillatory responses upon processing the painful laser stimulations. Our results show that painful laser stimulations enhanced low-gamma (LH, 40-70 Hz) and high-gamma (HG, 70-110 Hz) oscillatory responses in the amygdala and hippocampal regions on the right hemisphere and these gamma responses were significantly coupled with the phases of theta (4-7 Hz) and alpha (8-1 2 Hz) rhythms during pain processing. Given the roles of these deep brain structures in emotion, these findings suggest that the oscillatory responses in these regions may play a role in integrating the affective component of pain, which may contribute to our understanding of the mechanisms underlying the affective information processing in humans. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Accurate CT-MR image registration for deep brain stimulation: a multi-observer evaluation study

NASA Astrophysics Data System (ADS)

Rühaak, Jan; Derksen, Alexander; Heldmann, Stefan; Hallmann, Marc; Meine, Hans

2015-03-01

Since the first clinical interventions in the late 1980s, Deep Brain Stimulation (DBS) of the subthalamic nucleus has evolved into a very effective treatment option for patients with severe Parkinson's disease. DBS entails the implantation of an electrode that performs high frequency stimulations to a target area deep inside the brain. A very accurate placement of the electrode is a prerequisite for positive therapy outcome. The assessment of the intervention result is of central importance in DBS treatment and involves the registration of pre- and postinterventional scans. In this paper, we present an image processing pipeline for highly accurate registration of postoperative CT to preoperative MR. Our method consists of two steps: a fully automatic pre-alignment using a detection of the skull tip in the CT based on fuzzy connectedness, and an intensity-based rigid registration. The registration uses the Normalized Gradient Fields distance measure in a multilevel Gauss-Newton optimization framework and focuses on a region around the subthalamic nucleus in the MR. The accuracy of our method was extensively evaluated on 20 DBS datasets from clinical routine and compared with manual expert registrations. For each dataset, three independent registrations were available, thus allowing to relate algorithmic with expert performance. Our method achieved an average registration error of 0.95mm in the target region around the subthalamic nucleus as compared to an inter-observer variability of 1.12 mm. Together with the short registration time of about five seconds on average, our method forms a very attractive package that can be considered ready for clinical use.

Computational models of Bitemporal, Bifrontal and Right Unilateral ECT predict differential stimulation of brain regions associated with efficacy and cognitive side effects.

PubMed

Bai, S; Gálvez, V; Dokos, S; Martin, D; Bikson, M; Loo, C

2017-03-01

Extensive clinical research has shown that the efficacy and cognitive outcomes of electroconvulsive therapy (ECT) are determined, in part, by the type of electrode placement used. Bitemporal ECT (BT, stimulating electrodes placed bilaterally in the frontotemporal region) is the form of ECT with relatively potent clinical and cognitive side effects. However, the reasons for this are poorly understood. This study used computational modelling to examine regional differences in brain excitation between BT, Bifrontal (BF) and Right Unilateral (RUL) ECT, currently the most clinically-used ECT placements. Specifically, by comparing similarities and differences in current distribution patterns between BT ECT and the other two placements, the study aimed to create an explanatory model of critical brain sites that mediate antidepressant efficacy and sites associated with cognitive, particularly memory, adverse effects. High resolution finite element human head models were generated from MRI scans of three subjects. The models were used to compare differences in activation between the three ECT placements, using subtraction maps. In this exploratory study on three realistic head models, Bitemporal ECT resulted in greater direct stimulation of deep midline structures and also left temporal and inferior frontal regions. Interpreted in light of existing knowledge on depressive pathophysiology and cognitive neuroanatomy, it is suggested that the former sites are related to efficacy and the latter to cognitive deficits. We hereby propose an approach using binarised subtraction models that can be used to optimise, and even individualise, ECT therapies. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Mapping the fine structure of cortical activity with different micro-ECoG electrode array geometries

NASA Astrophysics Data System (ADS)

Wang, Xi; Gkogkidis, C. Alexis; Iljina, Olga; Fiederer, Lukas D. J.; Henle, Christian; Mader, Irina; Kaminsky, Jan; Stieglitz, Thomas; Gierthmuehlen, Mortimer; Ball, Tonio

2017-10-01

Objective. Innovations in micro-electrocorticography (µECoG) electrode array manufacturing now allow for intricate designs with smaller contact diameters and/or pitch (i.e. inter-contact distance) down to the sub-mm range. The aims of the present study were: (i) to investigate whether frequency ranges up to 400 Hz can be reproducibly observed in µECoG recordings and (ii) to examine how differences in topographical substructure between these frequency bands and electrode array geometries can be quantified. We also investigated, for the first time, the influence of blood vessels on signal properties and assessed the influence of cortical vasculature on topographic mapping. Approach. The present study employed two µECoG electrode arrays with different contact diameters and inter-contact distances, which were used to characterize neural activity from the somatosensory cortex of minipigs in a broad frequency range up to 400 Hz. The analysed neural data were recorded in acute experiments under anaesthesia during peripheral electrical stimulation. Main results. We observed that µECoG recordings reliably revealed multi-focal cortical somatosensory response patterns, in which response peaks were often less than 1 cm apart and would thus not have been resolvable with conventional ECoG. The response patterns differed by stimulation site and intensity, they were distinct for different frequency bands, and the results of functional mapping proved independent of cortical vascular. Our analysis of different frequency bands exhibited differences in the number of activation peaks in topographical substructures. Notably, signal strength and signal-to-noise ratios differed between the two electrode arrays, possibly due to their different sensitivity for variations in spatial patterns and signal strengths. Significance. Our findings that the geometry of µECoG electrode arrays can strongly influence their recording performance can help to make informed decisions that maybe important in number of clinical contexts, including high-resolution brain mapping, advanced epilepsy diagnostics or brain-machine interfacing.

Toward defining deep brain stimulation targets in MNI space: A subcortical atlas based on multimodal MRI, histology and structural connectivity.

PubMed

Ewert, Siobhan; Plettig, Philip; Li, Ningfei; Chakravarty, M Mallar; Collins, D Louis; Herrington, Todd M; Kühn, Andrea A; Horn, Andreas

2018-04-15

Three-dimensional atlases of subcortical brain structures are valuable tools to reference anatomy in neuroscience and neurology. For instance, they can be used to study the position and shape of the three most common deep brain stimulation (DBS) targets, the subthalamic nucleus (STN), internal part of the pallidum (GPi) and ventral intermediate nucleus of the thalamus (VIM) in spatial relationship to DBS electrodes. Here, we present a composite atlas based on manual segmentations of a multimodal high resolution brain template, histology and structural connectivity. In a first step, four key structures were defined on the template itself using a combination of multispectral image analysis and manual segmentation. Second, these structures were used as anchor points to coregister a detailed histological atlas into standard space. Results show that this approach significantly improved coregistration accuracy over previously published methods. Finally, a sub-segmentation of STN and GPi into functional zones was achieved based on structural connectivity. The result is a composite atlas that defines key nuclei on the template itself, fills the gaps between them using histology and further subdivides them using structural connectivity. We show that the atlas can be used to segment DBS targets in single subjects, yielding more accurate results compared to priorly published atlases. The atlas will be made publicly available and constitutes a resource to study DBS electrode localizations in combination with modern neuroimaging methods. Copyright © 2017 Elsevier Inc. All rights reserved.

Close-field electroporation gene delivery using the cochlear implant electrode array enhances the bionic ear.

PubMed

Pinyon, Jeremy L; Tadros, Sherif F; Froud, Kristina E; Y Wong, Ann C; Tompson, Isabella T; Crawford, Edward N; Ko, Myungseo; Morris, Renée; Klugmann, Matthias; Housley, Gary D

2014-04-23

The cochlear implant is the most successful bionic prosthesis and has transformed the lives of people with profound hearing loss. However, the performance of the "bionic ear" is still largely constrained by the neural interface itself. Current spread inherent to broad monopolar stimulation of the spiral ganglion neuron somata obviates the intrinsic tonotopic mapping of the cochlear nerve. We show in the guinea pig that neurotrophin gene therapy integrated into the cochlear implant improves its performance by stimulating spiral ganglion neurite regeneration. We used the cochlear implant electrode array for novel "close-field" electroporation to transduce mesenchymal cells lining the cochlear perilymphatic canals with a naked complementary DNA gene construct driving expression of brain-derived neurotrophic factor (BDNF) and a green fluorescent protein (GFP) reporter. The focusing of electric fields by particular cochlear implant electrode configurations led to surprisingly efficient gene delivery to adjacent mesenchymal cells. The resulting BDNF expression stimulated regeneration of spiral ganglion neurites, which had atrophied 2 weeks after ototoxic treatment, in a bilateral sensorineural deafness model. In this model, delivery of a control GFP-only vector failed to restore neuron structure, with atrophied neurons indistinguishable from unimplanted cochleae. With BDNF therapy, the regenerated spiral ganglion neurites extended close to the cochlear implant electrodes, with localized ectopic branching. This neural remodeling enabled bipolar stimulation via the cochlear implant array, with low stimulus thresholds and expanded dynamic range of the cochlear nerve, determined via electrically evoked auditory brainstem responses. This development may broadly improve neural interfaces and extend molecular medicine applications.

Cocaine enhances resistance to extinction of responding for brain-stimulation reward in adult prenatally stressed rats.

PubMed

Gao, Shuibo; Suenaga, Toshiko; Oki, Yutaka; Yukie, Masao; Nakahara, Daiichiro

2011-10-01

The present experiment assessed whether prenatal stress (PS) can alter the ability of acute and chronic cocaine administration to increase and decrease the rewarding effectiveness of the medial forebrain bundle (MFB) using intracranial self-stimulation (ICSS), and also whether PS can affect the extinction of the MFB stimulation response. Adult male offspring of female rats that received PS or no PS (nPS) were implanted with MFB stimulating electrodes, and were then tested in ICSS paradigms. In both nPS and PS offspring, acute cocaine injection decreased ICSS thresholds dose-dependently. However, the threshold-lowering effects at any dose were not significantly different between groups. There was also no group-difference in the threshold-elevating effects of chronic cocaine administration. Nevertheless, chronically drug-administered PS rats exhibited a resistance to the extinguishing of the response for brain-stimulation reward when acutely treated with cocaine, as compared to extinction without cocaine treatment. The results suggest that PS may weaken the ability for response inhibition under cocaine loading in male adult offspring. Copyright © 2011 Elsevier B.V. All rights reserved.

Low-frequency stimulation of the external globus palladium produces anti-epileptogenic and anti-ictogenic actions in rats

PubMed Central

Cheng, Hui; Kuang, Yi-fang; Liu, Yang; Wang, Yi; Xu, Zheng-hao; Gao, Feng; Zhang, Shi-hong; Ding, Mei-ping; Chen, Zhong

2015-01-01

Aim: To investigate the anti-epileptic effects of deep brain stimulation targeting the external globus palladium (GPe) in rats. Methods: For inducing amygdala kindling and deep brain stimulation, bipolar stainless-steel electrodes were implanted in SD rats into right basolateral amygdala and right GPe, respectively. The effects of deep brain stimulation were evaluated in the amygdala kindling model, maximal electroshock model (MES) and pentylenetetrazole (PTZ) model. Moreover, the background EEGs in the amygdala and GPe were recorded. Results: Low-frequency stimulation (0.1 ms, 1 Hz, 15 min) at the GPe slowed the progression of seizure stages and shortened the after-discharge duration (ADD) during kindling acquisition. Furthermore, low-frequency stimulation significantly decreased the incidence of generalized seizures, suppressed the average stage, and shortened the cumulative ADD and generalized seizure duration in fully kindled rats. In addition, low-frequency stimulation significantly suppressed the average stage of MES-induced seizures and increased the latency to generalized seizures in the PTZ model. High-frequency stimulation (0.1 ms, 130 Hz, 5 min) at the GPe had no anti-epileptic effect and even aggravated epileptogenesis induced by amygdala kindling. EEG analysis showed that low-frequency stimulation at the GPe reversed the increase in delta power, whereas high-frequency stimulation at the GPe had no such effect. Conclusion: Low-frequency stimulation, but not high-frequency stimulation, at the GPe exerts therapeutic effect on temporal lobe epilepsy and tonic-colonic generalized seizures, which may be due to interference with delta rhythms. The results suggest that modulation of GPe activity using low-frequency stimulation or drugs may be a promising epilepsy treatment. PMID:26095038

Desynchronizing electrical and sensory coordinated reset neuromodulation

PubMed Central

Popovych, Oleksandr V.; Tass, Peter A.

2012-01-01

Coordinated reset (CR) stimulation is a desynchronizing stimulation technique based on timely coordinated phase resets of sub-populations of a synchronized neuronal ensemble. It has initially been computationally developed for electrical deep brain stimulation (DBS), to enable an effective desynchronization and unlearning of pathological synchrony and connectivity (anti-kindling). Here we computationally show for ensembles of spiking and bursting model neurons interacting via excitatory and inhibitory adaptive synapses that a phase reset of neuronal populations as well as a desynchronization and an anti-kindling can robustly be achieved by direct electrical stimulation or indirect (synaptically-mediated) excitatory and inhibitory stimulation. Our findings are relevant for DBS as well as for sensory stimulation in neurological disorders characterized by pathological neuronal synchrony. Based on the obtained results, we may expect that the local effects in the vicinity of a depth electrode (realized by direct stimulation of the neurons' somata or stimulation of axon terminals) and the non-local CR effects (realized by stimulation of excitatory or inhibitory efferent fibers) of deep brain CR neuromodulation may be similar or even identical. Furthermore, our results indicate that an effective desynchronization and anti-kindling can even be achieved by non-invasive, sensory CR neuromodulation. We discuss the concept of sensory CR neuromodulation in the context of neurological disorders. PMID:22454622

Desynchronizing electrical and sensory coordinated reset neuromodulation.

PubMed

Popovych, Oleksandr V; Tass, Peter A

2012-01-01

Coordinated reset (CR) stimulation is a desynchronizing stimulation technique based on timely coordinated phase resets of sub-populations of a synchronized neuronal ensemble. It has initially been computationally developed for electrical deep brain stimulation (DBS), to enable an effective desynchronization and unlearning of pathological synchrony and connectivity (anti-kindling). Here we computationally show for ensembles of spiking and bursting model neurons interacting via excitatory and inhibitory adaptive synapses that a phase reset of neuronal populations as well as a desynchronization and an anti-kindling can robustly be achieved by direct electrical stimulation or indirect (synaptically-mediated) excitatory and inhibitory stimulation. Our findings are relevant for DBS as well as for sensory stimulation in neurological disorders characterized by pathological neuronal synchrony. Based on the obtained results, we may expect that the local effects in the vicinity of a depth electrode (realized by direct stimulation of the neurons' somata or stimulation of axon terminals) and the non-local CR effects (realized by stimulation of excitatory or inhibitory efferent fibers) of deep brain CR neuromodulation may be similar or even identical. Furthermore, our results indicate that an effective desynchronization and anti-kindling can even be achieved by non-invasive, sensory CR neuromodulation. We discuss the concept of sensory CR neuromodulation in the context of neurological disorders.

Phase dependent modulation of tremor amplitude in essential tremor through thalamic stimulation

PubMed Central

Cagnan, Hayriye; Brittain, John-Stuart; Little, Simon; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Joint, Carole; Fitzgerald, James; Green, Alexander L.; Aziz, Tipu

2013-01-01

High frequency deep brain stimulation of the thalamus can help ameliorate severe essential tremor. Here we explore how the efficacy, efficiency and selectivity of thalamic deep brain stimulation might be improved in this condition. We started from the hypothesis that the effects of electrical stimulation on essential tremor may be phase dependent, and that, in particular, there are tremor phases at which stimuli preferentially lead to a reduction in the amplitude of tremor. The latter could be exploited to improve deep brain stimulation, particularly if tremor suppression could be reinforced by cumulative effects. Accordingly, we stimulated 10 patients with essential tremor and thalamic electrodes, while recording tremor amplitude and phase. Stimulation near the postural tremor frequency entrained tremor. Tremor amplitude was also modulated depending on the phase at which stimulation pulses were delivered in the tremor cycle. Stimuli in one half of the tremor cycle reduced median tremor amplitude by ∼10%, while those in the opposite half of the tremor cycle increased tremor amplitude by a similar amount. At optimal phase alignment tremor suppression reached 27%. Moreover, tremor amplitude showed a non-linear increase in the degree of suppression with successive stimuli; tremor suppression was increased threefold if a stimulus was preceded by four stimuli with a similar phase relationship with respect to the tremor, suggesting cumulative, possibly plastic, effects. The present results pave the way for a stimulation system that tracks tremor phase to control when deep brain stimulation pulses are delivered to treat essential tremor. This would allow treatment effects to be maximized by focussing stimulation on the optimal phase for suppression and by ensuring that this is repeated over many cycles so as to harness cumulative effects. Such a system might potentially achieve tremor control with far less power demand and greater specificity than current high frequency stimulation approaches, and may lower the risk for tolerance and rebound. PMID:24038075

Carbon-Nanotube-Based Electrodes for Biomedical Applications

NASA Technical Reports Server (NTRS)

Li, Jun; Meyyappan, M.

2008-01-01

A nanotube array based on vertically aligned nanotubes or carbon nanofibers has been invented for use in localized electrical stimulation and recording of electrical responses in selected regions of an animal body, especially including the brain. There are numerous established, emerging, and potential applications for localized electrical stimulation and/or recording, including treatment of Parkinson s disease, Tourette s syndrome, and chronic pain, and research on electrochemical effects involved in neurotransmission. Carbon-nanotube-based electrodes offer potential advantages over metal macroelectrodes (having diameters of the order of a millimeter) and microelectrodes (having various diameters ranging down to tens of microns) heretofore used in such applications. These advantages include the following: a) Stimuli and responses could be localized at finer scales of spatial and temporal resolution, which is at subcellular level, with fewer disturbances to, and less interference from, adjacent regions. b) There would be less risk of hemorrhage on implantation because nano-electrode-based probe tips could be configured to be less traumatic. c) Being more biocompatible than are metal electrodes, carbon-nanotube-based electrodes and arrays would be more suitable for long-term or permanent implantation. d) Unlike macro- and microelectrodes, a nano-electrode could penetrate a cell membrane with minimal disruption. Thus, for example, a nanoelectrode could be used to generate an action potential inside a neuron or in proximity of an active neuron zone. Such stimulation may be much more effective than is extra- or intracellular stimulation via a macro- or microelectrode. e) The large surface area of an array at a micron-scale footprint of non-insulated nanoelectrodes coated with a suitable electrochemically active material containing redox ingredients would make it possible to obtain a pseudocapacitance large enough to dissipate a relatively large amount of electric charge, so that a large stimulation current could be applied at a micron-scale region without exhausting the redox ingredients. f) Carbon nanotube array is more compatible with the three-dimensional network of tissues. Particularly, a better electrical-neural interface can be formed. g) A carbon nanotube array inlaid in insulating materials with only the ends exposed is an extremely sensitive electro-analysis tool that can measure the local neurotransmitter signal at extremely high sensitivity and temporal resolution.

Shielded Coaxial Optrode Arrays for Neurophysiology

PubMed Central

Naughton, Jeffrey R.; Connolly, Timothy; Varela, Juan A.; Lundberg, Jaclyn; Burns, Michael J.; Chiles, Thomas C.; Christianson, John P.; Naughton, Michael J.

2016-01-01

Recent progress in the study of the brain has been greatly facilitated by the development of new tools capable of minimally-invasive, robust coupling to neuronal assemblies. Two prominent examples are the microelectrode array (MEA), which enables electrical signals from large numbers of neurons to be detected and spatiotemporally correlated, and optogenetics, which enables the electrical activity of cells to be controlled with light. In the former case, high spatial density is desirable but, as electrode arrays evolve toward higher density and thus smaller pitch, electrical crosstalk increases. In the latter, finer control over light input is desirable, to enable improved studies of neuroelectronic pathways emanating from specific cell stimulation. Here, we introduce a coaxial electrode architecture that is uniquely suited to address these issues, as it can simultaneously be utilized as an optical waveguide and a shielded electrode in dense arrays. Using optogenetically-transfected cells on a coaxial MEA, we demonstrate the utility of the architecture by recording cellular currents evoked from optical stimulation. We also show the capability for network recording by radiating an area of seven individually-addressed coaxial electrode regions with cultured cells covering a section of the extent. PMID:27375415

Interpulse interval discrimination within and across channels: comparison of monopolar and tripolar mode of stimulation.

PubMed

Fielden, Claire A; Kluk, Karolina; McKay, Colette M

2014-05-01

Perception of temporal patterns is crucial to speech understanding and music perception in normal hearing, and is fundamental in the design and implementation of processing strategies for cochlear implants. Two experiments described here investigated the effect of stimulation mode (monopolar versus tripolar) on interpulse interval discrimination using single-electrode stimulation (experiment 1) and dual-electrode stimulation (experiment 2). Experiment 1 required participants to discriminate stimuli containing different interpulse intervals and experiment 2 required listeners to discriminate between two dual-electrode stimuli that had the same temporal pattern on each electrode, but differed in inter-electrode timing. The hypotheses were that (i) stimulation mode would affect the ability to distinguish interpulse interval patterns on a single electrode and (ii) the electrode separation range in which subjects were sensitive to inter-electrode timing would be more restricted in tripolar than in monopolar stimulation. Results in nine cochlear implant users showed that mode did not have a significant mean effect on either the ability to discriminate interpulse intervals in single-electrode stimulation or the range of electrode separation in dual-electrode stimulation in which participants were sensitive to inter-electrode timing. In conclusion, tripolar stimulation did not show any advantage in delivering temporal information within or across channels in this group.

Deep Brain Stimulation: A Paradigm Shifting Approach to Treat Parkinson's Disease.

PubMed

Hickey, Patrick; Stacy, Mark

2016-01-01

Parkinson disease (PD) is a chronic and progressive movement disorder classically characterized by slowed voluntary movements, resting tremor, muscle rigidity, and impaired gait and balance. Medical treatment is highly successful early on, though the majority of people experience significant complications in later stages. In advanced PD, when medications no longer adequately control motor symptoms, deep brain stimulation (DBS) offers a powerful therapeutic alternative. DBS involves the surgical implantation of one or more electrodes into specific areas of the brain, which modulate or disrupt abnormal patterns of neural signaling within the targeted region. Outcomes are often dramatic following DBS, with improvements in motor function and reductions motor complications having been repeatedly demonstrated. Given such robust responses, emerging indications for DBS are being investigated. In parallel with expansions of therapeutic scope, advancements within the areas of neurosurgical technique and the precision of stimulation delivery have recently broadened as well. This review focuses on the revolutionary addition of DBS to the therapeutic armamentarium for PD, and summarizes the technological advancements in the areas of neuroimaging and biomedical engineering intended to improve targeting, programming, and overall management.

Electric field characteristics of electroconvulsive therapy with individualized current amplitude: a preclinical study.

PubMed

Lee, Won Hee; Lisanby, Sarah H; Laine, Andrew F; Peterchev, Angel V

2013-01-01

This study examines the characteristics of the electric field induced in the brain by electroconvulsive therapy (ECT) with individualized current amplitude. The electric field induced by bilateral (BL), bifrontal (BF), right unilateral (RUL), and frontomedial (FM) ECT electrode configurations was computed in anatomically realistic finite element models of four nonhuman primates (NHPs). We generated maps of the electric field strength relative to an empirical neural activation threshold, and determined the stimulation strength and focality at fixed current amplitude and at individualized current amplitudes corresponding to seizure threshold (ST) measured in the anesthetized NHPs. The results show less variation in brain volume stimulated above threshold with individualized current amplitudes (16-36%) compared to fixed current amplitude (30-62%). Further, the stimulated brain volume at amplitude-titrated ST is substantially lower than that for ECT with conventional fixed current amplitudes. Thus individualizing the ECT stimulus current could compensate for individual anatomical variability and result in more focal and uniform electric field exposure across different subjects compared to the standard clinical practice of using high, fixed current for all patients.

Deep brain stimulation for severe treatment-resistant obsessive-compulsive disorder: An open-label case series.

PubMed

Farrand, Sarah; Evans, Andrew H; Mangelsdorf, Simone; Loi, Samantha M; Mocellin, Ramon; Borham, Adam; Bevilacqua, JoAnne; Blair-West, Scott; Walterfang, Mark A; Bittar, Richard G; Velakoulis, Dennis

2017-09-01

Deep brain stimulation can be of benefit in carefully selected patients with severe intractable obsessive-compulsive disorder. The aim of this paper is to describe the outcomes of the first seven deep brain stimulation procedures for obsessive-compulsive disorder undertaken at the Neuropsychiatry Unit, Royal Melbourne Hospital. The primary objective was to assess the response to deep brain stimulation treatment utilising the Yale-Brown Obsessive Compulsive Scale as a measure of symptom severity. Secondary objectives include assessment of depression and anxiety, as well as socio-occupational functioning. Patients with severe obsessive-compulsive disorder were referred by their treating psychiatrist for assessment of their suitability for deep brain stimulation. Following successful application to the Psychosurgery Review Board, patients proceeded to have deep brain stimulation electrodes implanted in either bilateral nucleus accumbens or bed nucleus of stria terminalis. Clinical assessment and symptom rating scales were undertaken pre- and post-operatively at 6- to 8-week intervals. Rating scales used included the Yale-Brown Obsessive Compulsive Scale, Obsessive Compulsive Inventory, Depression Anxiety Stress Scale and Social and Occupational Functioning Assessment Scale. Seven patients referred from four states across Australia underwent deep brain stimulation surgery and were followed for a mean of 31 months (range, 8-54 months). The sample included four females and three males, with a mean age of 46 years (range, 37-59 years) and mean duration of obsessive-compulsive disorder of 25 years (range, 15-38 years) at the time of surgery. The time from first assessment to surgery was on average 18 months. All patients showed improvement on symptom severity rating scales. Three patients showed a full response, defined as greater than 35% improvement in Yale-Brown Obsessive Compulsive Scale score, with the remaining showing responses between 7% and 20%. Deep brain stimulation was an effective treatment for obsessive-compulsive disorder in these highly selected patients. The extent of the response to deep brain stimulation varied between patients, as well as during the course of treatment for each patient. The results of this series are comparable with the literature, as well as having similar efficacy to ablative psychosurgery techniques such as capsulotomy and cingulotomy. Deep brain stimulation provides advantages over lesional psychosurgery but is more expensive and requires significant multidisciplinary input at all stages, pre- and post-operatively, ideally within a specialised tertiary clinical and/or academic centre. Ongoing research is required to better understand the neurobiological basis for obsessive-compulsive disorder and how this can be manipulated with deep brain stimulation to further improve the efficacy of this emerging treatment.

Violence, mental illness, and the brain – A brief history of psychosurgery: Part 2 – From the limbic system and cingulotomy to deep brain stimulation

PubMed Central

Faria, Miguel A.

2013-01-01

Knowledge of neuroscience flourished during and in the wake of the era of frontal lobotomy, as a byproduct of psychosurgery in the late 1930s and 1940s, revealing fascinating neural pathways and neurophysiologic mechanisms of the limbic system for the formulation of emotions, memory, and human behavior. The creation of the Klüver-Bucy syndrome in monkeys opened new horizons in the pursuit of knowledge in human behavior and neuropathology. In the 1950s specialized functional neurosurgery was developed in association with stereotactic neurosurgery; deep brain electrodes were implanted for more precise recording of brain electrical activity in the evaluation and treatment of intractable mental disorders, including schizophrenia, “pathologic aggression,” and psychomotor seizures in temporal lobe epilepsy. Psychosurgical procedures involved deep brain stimulation of the limbic system, as well as ablative procedures, such as cingulotomy and thalamotomy. The history of these developments up to the 21st century will continue in this three-part essay-editorial, exclusively researched and written for the readers of Surgical Neurology International. PMID:23776761

A finite element analysis of the effect of electrode area and inter-electrode distance on the spatial distribution of the current density in tDCS

NASA Astrophysics Data System (ADS)

Faria, Paula; Hallett, Mark; Cavaleiro Miranda, Pedro

2011-12-01

We investigated the effect of electrode area and inter-electrode distance on the spatial distribution of the current density in transcranial direct current stimulation (tDCS). For this purpose, we used the finite element method to compute the distribution of the current density in a four-layered spherical head model using various electrode montages, corresponding to a range of electrode sizes and inter-electrode distances. We found that smaller electrodes required slightly less current to achieve a constant value of the current density at a reference point on the brain surface located directly under the electrode center. Under these conditions, smaller electrodes also produced a more focal current density distribution in the brain, i.e. the magnitude of the current density fell more rapidly with distance from the reference point. The combination of two electrodes with different areas produced an asymmetric current distribution that could lead to more effective and localized neural modulation under the smaller electrode than under the larger one. Focality improved rapidly with decreasing electrode size when the larger electrode sizes were considered but the improvement was less marked for the smaller electrode sizes. Also, focality was not affected significantly by inter-electrode distance unless two large electrodes were placed close together. Increasing the inter-electrode distance resulted in decreased shunting of the current through the scalp and the cerebrospinal fluid, and decreasing electrode area resulted in increased current density on the scalp under the edges of the electrode. Our calculations suggest that when working with conventional electrodes (25-35 cm2), one of the electrodes should be placed just 'behind' the target relative to the other electrode, for maximum current density on the target. Also electrodes with areas in the range 3.5-12 cm2 may provide a better compromise between focality and current density in the scalp than the traditional electrodes. Finally, the use of multiple small return electrodes may be more efficient than the use of a single large return electrode.

A temporary local energy pool coupled to neuronal activity: fluctuations of extracellular lactate levels in rat brain monitored with rapid-response enzyme-based sensor.

PubMed

Hu, Y; Wilson, G S

1997-10-01

A successfully developed enzyme-based lactate microsensor with rapid response time allows the direct and continuous in vivo measurement of lactic acid concentration with high temporal resolution in brain extracellular fluid. The fluctuations coupled to neuronal activity in extracellular lactate concentration were explored in the dentate gyrus of the hippocampus of the rat brain after electrical stimulation of the perforant pathway. Extracellular glucose and oxygen levels were also detected simultaneously by coimplantation of a fast-response glucose sensor and an oxygen electrode, to provide novel information of trafficking of energy substances in real time related to local neuronal activity. The results first give a comprehensive picture of complementary energy supply and use of lactate and glucose in the intact brain tissue. In response to acute neuronal activation, the brain tissue shifts immediately to significant energy supply by lactate. A local temporary fuel "reservoir" is established behind the blood-brain barrier, evidenced by increased extracellular lactate concentration. The pool can be depleted rapidly, up to 28% in 10-12 s, by massive, acute neuronal use after stimulation and can be replenished in approximately 20 s. Glutamate-stimulated astrocytic glycolysis and the increase of regional blood flow may regulate the lactate concentration of the pool in different time scales to maintain local energy homeostasis.

An unusual complication of invasive video-EEG monitoring: subelectrode hematoma without subdural component: case report.

PubMed

Bozkurt, Gokhan; Ayhan, Selim; Dericioglu, Nese; Saygi, Serap; Akalan, Nejat

2010-08-01

The potential complications of the subdural electrode implantation providing identification of the seizure focus and direct stimulation of the cerebral cortex for defining the eloquent cortical areas are epidural and subdural hematoma, cortical contusions, infection, brain edema, raised intracranial pressure, CSF leakage, and venous infarction have been previously reported in the literature. To present the first case of subelectrode hematoma without subdural component that was detected during invasive EEG monitoring after subdural electrode implantation. A 19-year-old female with drug resistant seizures was decided to undergo invasive monitoring with subdural electrodes. While good quality recordings had been initially obtained from all electrodes placed on the right parietal convexity, no cerebral cortical activity could be obtained from one electrode 2 days after the first operation. Explorative surgery revealed a circumscribed subelectrode hematoma without a subdural component. Awareness of the potential complications of subdural electrode implantation and close follow-up of the clinical findings of the patient are of highest value for early detection and successful management.

Progressive gait ataxia following deep brain stimulation for essential tremor: adverse effect or lack of efficacy?

PubMed

Reich, Martin M; Brumberg, Joachim; Pozzi, Nicolò G; Marotta, Giorgio; Roothans, Jonas; Åström, Mattias; Musacchio, Thomas; Lopiano, Leonardo; Lanotte, Michele; Lehrke, Ralph; Buck, Andreas K; Volkmann, Jens; Isaias, Ioannis U

2016-11-01

Thalamic deep brain stimulation is a mainstay treatment for severe and drug-refractory essential tremor, but postoperative management may be complicated in some patients by a progressive cerebellar syndrome including gait ataxia, dysmetria, worsening of intention tremor and dysarthria. Typically, this syndrome manifests several months after an initially effective therapy and necessitates frequent adjustments in stimulation parameters. There is an ongoing debate as to whether progressive ataxia reflects a delayed therapeutic failure due to disease progression or an adverse effect related to repeated increases of stimulation intensity. In this study we used a multimodal approach comparing clinical stimulation responses, modelling of volume of tissue activated and metabolic brain maps in essential tremor patients with and without progressive ataxia to disentangle a disease-related from a stimulation-induced aetiology. Ten subjects with stable and effective bilateral thalamic stimulation were stratified according to the presence (five subjects) of severe chronic-progressive gait ataxia. We quantified stimulated brain areas and identified the stimulation-induced brain metabolic changes by multiple 18 F-fluorodeoxyglucose positron emission tomography performed with and without active neurostimulation. Three days after deactivating thalamic stimulation and following an initial rebound of symptom severity, gait ataxia had dramatically improved in all affected patients, while tremor had worsened to the presurgical severity, thus indicating a stimulation rather than disease-related phenomenon. Models of the volume of tissue activated revealed a more ventrocaudal stimulation in the (sub)thalamic area of patients with progressive gait ataxia. Metabolic maps of both patient groups differed by an increased glucose uptake in the cerebellar nodule of patients with gait ataxia. Our data suggest that chronic progressive gait ataxia in essential tremor is a reversible cerebellar syndrome caused by a maladaptive response to neurostimulation of the (sub)thalamic area. The metabolic signature of progressive gait ataxia is an activation of the cerebellar nodule, which may be caused by inadvertent current spread and antidromic stimulation of a cerebellar outflow pathway originating in the vermis. An anatomical candidate could be the ascending limb of the uncinate tract in the subthalamic area. Adjustments in programming and precise placement of the electrode may prevent this adverse effect and help fine-tuning deep brain stimulation to ameliorate tremor without negative cerebellar signs. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Deep brain stimulation macroelectrodes compared to multiple microelectrodes in rat hippocampus

PubMed Central

Arcot Desai, Sharanya; Gutekunst, Claire-Anne; Potter, Steve M.; Gross, Robert E.

2014-01-01

Microelectrode arrays (wire diameter <50 μm) were compared to traditional macroelectrodes for deep brain stimulation (DBS). Understanding the neuronal activation volume may help solve some of the mysteries associated with DBS, e.g., its mechanisms of action. We used c-fos immunohistochemistry to investigate neuronal activation in the rat hippocampus caused by multi-micro- and macroelectrode stimulation. At ± 1V stimulation at 25 Hz, microelectrodes (33 μm diameter) had a radius of activation of 100 μm, which is 50% of that seen with 150 μm diameter macroelectrode stimulation. Macroelectrodes activated about 5.8 times more neurons than a single microelectrode, but displaced ~20 times more neural tissue. The sphere of influence of stimulating electrodes can be significantly increased by reducing their impedance. By ultrasonic electroplating (sonicoplating) the microelectrodes with platinum to increase their surface area and reduce their impedance by an order of magnitude, the radius of activation increased by 50 μm and more than twice the number of neurons were activated within this increased radius compared to unplated microelectrodes. We suggest that a new approach to DBS, one that uses multiple high-surface area microelectrodes, may be more therapeutically effective due to increased neuronal activation. PMID:24971060

Image-guided preoperative prediction of pyramidal tract side effect in deep brain stimulation: proof of concept and application to the pyramidal tract side effect induced by pallidal stimulation.

PubMed

Baumgarten, Clement; Zhao, Yulong; Sauleau, Paul; Malrain, Cecile; Jannin, Pierre; Haegelen, Claire

2016-04-01

Deep brain stimulation of the medial globus pallidus (GPm) is a surgical procedure for treating patients suffering from Parkinson's disease. Its therapeutic effect may be limited by the presence of pyramidal tract side effect (PTSE). PTSE is a contraction time-locked to the stimulation when the current spreading reaches the motor fibers of the pyramidal tract within the internal capsule. The objective of the study was to propose a preoperative predictive model of PTSE. A machine learning-based method called PyMAN (PTSE model based on artificial neural network) accounting for the current used in stimulation, the three-dimensional electrode coordinates and the angle of the trajectory, was designed to predict the occurrence of PTSE. Ten patients implanted in the GPm have been tested by a clinician to create a labeled dataset of the stimulation parameters that trigger PTSE. The kappa index value between the data predicted by PyMAN and the labeled data was 0.78. Further evaluation studies are desirable to confirm whether PyMAN could be a reliable tool for assisting the surgeon to prevent PTSE during the preoperative planning.

Pediatric stroke and transcranial direct current stimulation: methods for rational individualized dose optimization

PubMed Central

Gillick, Bernadette T.; Kirton, Adam; Carmel, Jason B.; Minhas, Preet; Bikson, Marom

2014-01-01

Background: Transcranial direct current stimulation (tDCS) has been investigated mainly in adults and doses may not be appropriate in pediatric applications. In perinatal stroke where potential applications are promising, rational adaptation of dosage for children remains under investigation. Objective: Construct child-specific tDCS dosing parameters through case study within a perinatal stroke tDCS safety and feasibility trial. Methods: 10-year-old subject with a diagnosis of presumed perinatal ischemic stroke and hemiparesis was identified. T1 magnetic resonance imaging (MRI) scans used to derive computerized model for current flow and electrode positions. Workflow using modeling results and consideration of dosage in previous clinical trials was incorporated. Prior ad hoc adult montages vs. de novo optimized montages provided distinct risk benefit analysis. Approximating adult dose required consideration of changes in both peak brain current flow and distribution which further tradeoff between maximizing efficacy and adding safety factors. Electrode size, position, current intensity, compliance voltage, and duration were controlled independently in this process. Results: Brain electric fields modeled and compared to values previously predicted models (Datta et al., 2011; Minhas et al., 2012). Approximating conservative brain current flow patterns and intensities used in previous adult trials for comparable indications, the optimal current intensity established was 0.7 mA for 10 min with a tDCS C3/C4 montage. Specifically 0.7 mA produced comparable peak brain current intensity of an average adult receiving 1.0 mA. Electrode size of 5 × 7 cm2 with 1.0 mA and low-voltage tDCS was employed to maximize tolerability. Safety and feasibility confirmed with subject tolerating the session well and no serious adverse events. Conclusion: Rational approaches to dose customization, with steps informed by computational modeling, may improve guidance for pediatric stroke tDCS trials. PMID:25285077

Determination of subthalamic nucleus location by quantitative analysis of despiked background neural activity from microelectrode recordings obtained during deep brain stimulation surgery.

PubMed

Danish, Shabbar F; Baltuch, Gordon H; Jaggi, Jurg L; Wong, Stephen

2008-04-01

Microelectrode recording during deep brain stimulation surgery is a useful adjunct for subthalamic nucleus (STN) localization. We hypothesize that information in the nonspike background activity can help identify STN boundaries. We present results from a novel quantitative analysis that accomplishes this goal. Thirteen consecutive microelectrode recordings were retrospectively analyzed. Spikes were removed from the recordings with an automated algorithm. The remaining "despiked" signals were converted via root mean square amplitude and curve length calculations into "feature profile" time series. Subthalamic nucleus boundaries determined by inspection, based on sustained deviations from baseline for each feature profile, were compared against those determined intraoperatively by the clinical neurophysiologist. Feature profile activity within STN exhibited a sustained rise in 10 of 13 tracks (77%). The sensitivity of STN entry was 60% and 90% for curve length and root mean square amplitude, respectively, when agreement within 0.5 mm of the neurophysiologist's prediction was used. Sensitivities were 70% and 100% for 1 mm accuracy. Exit point sensitivities were 80% and 90% for both features within 0.5 mm and 1.0 mm, respectively. Reproducible activity patterns in deep brain stimulation microelectrode recordings can allow accurate identification of STN boundaries. Quantitative analyses of this type may provide useful adjunctive information for electrode placement in deep brain stimulation surgery.

Simultaneous recording of fluorescence and electrical signals by photometric patch electrode in deep brain regions in vivo

PubMed Central

Hirai, Yasuharu; Nishino, Eri

2015-01-01

Despite its widespread use, high-resolution imaging with multiphoton microscopy to record neuronal signals in vivo is limited to the surface of brain tissue because of limited light penetration. Moreover, most imaging studies do not simultaneously record electrical neural activity, which is, however, crucial to understanding brain function. Accordingly, we developed a photometric patch electrode (PME) to overcome the depth limitation of optical measurements and also enable the simultaneous recording of neural electrical responses in deep brain regions. The PME recoding system uses a patch electrode to excite a fluorescent dye and to measure the fluorescence signal as a light guide, to record electrical signal, and to apply chemicals to the recorded cells locally. The optical signal was analyzed by either a spectrometer of high light sensitivity or a photomultiplier tube depending on the kinetics of the responses. We used the PME in Oregon Green BAPTA-1 AM-loaded avian auditory nuclei in vivo to monitor calcium signals and electrical responses. We demonstrated distinct response patterns in three different nuclei of the ascending auditory pathway. On acoustic stimulation, a robust calcium fluorescence response occurred in auditory cortex (field L) neurons that outlasted the electrical response. In the auditory midbrain (inferior colliculus), both responses were transient. In the brain-stem cochlear nucleus magnocellularis, calcium response seemed to be effectively suppressed by the activity of metabotropic glutamate receptors. In conclusion, the PME provides a powerful tool to study brain function in vivo at a tissue depth inaccessible to conventional imaging devices. PMID:25761950

Simultaneous recording of fluorescence and electrical signals by photometric patch electrode in deep brain regions in vivo.

PubMed

Hirai, Yasuharu; Nishino, Eri; Ohmori, Harunori

2015-06-01

Despite its widespread use, high-resolution imaging with multiphoton microscopy to record neuronal signals in vivo is limited to the surface of brain tissue because of limited light penetration. Moreover, most imaging studies do not simultaneously record electrical neural activity, which is, however, crucial to understanding brain function. Accordingly, we developed a photometric patch electrode (PME) to overcome the depth limitation of optical measurements and also enable the simultaneous recording of neural electrical responses in deep brain regions. The PME recoding system uses a patch electrode to excite a fluorescent dye and to measure the fluorescence signal as a light guide, to record electrical signal, and to apply chemicals to the recorded cells locally. The optical signal was analyzed by either a spectrometer of high light sensitivity or a photomultiplier tube depending on the kinetics of the responses. We used the PME in Oregon Green BAPTA-1 AM-loaded avian auditory nuclei in vivo to monitor calcium signals and electrical responses. We demonstrated distinct response patterns in three different nuclei of the ascending auditory pathway. On acoustic stimulation, a robust calcium fluorescence response occurred in auditory cortex (field L) neurons that outlasted the electrical response. In the auditory midbrain (inferior colliculus), both responses were transient. In the brain-stem cochlear nucleus magnocellularis, calcium response seemed to be effectively suppressed by the activity of metabotropic glutamate receptors. In conclusion, the PME provides a powerful tool to study brain function in vivo at a tissue depth inaccessible to conventional imaging devices. Copyright © 2015 the American Physiological Society.

The 3-dimensional grid: a novel approach to stereoelectroencephalography.

PubMed

Munyon, Charles; Sweet, Jennifer; Luders, Hans; Lhatoo, Samden; Miller, Jonathan

2015-03-01

Successful surgical treatment of epilepsy requires accurate definition of areas of ictal onset and eloquent brain. Although invasive monitoring can help, subdural grids cannot sample sulci or subcortical tissue; traditional stereoelectroencephalography depth electrodes are usually placed too far apart to provide sufficient resolution for mapping. To report a strategy of depth electrode placement in a dense array to allow precise anatomic localization of epileptic and eloquent cortex. Twenty patients with medically intractable epilepsy either poorly localized or found to arise adjacent to eloquent areas underwent placement of arrays of depth electrodes into and around the putative area of seizure onset with the use of framed stereotaxy. Each array consisted of a "grid" of parallel electrodes in a rectangular pattern with 1 cm between entry sites. In a subset of patients, a few electrodes were placed initially, with additional electrodes placed in a second stage. Trajectories were modified to avoid cortical vessels defined on magnetic resonance imaging. Patients were monitored for 4 to 21 days to establish the precise location of seizure onset. Stimulation was performed to map cortical and subcortical eloquent regions. Electrode locations were coregistered for frameless stereotaxy during subsequent resection of seizure focus. Two hundred fifty-four electrodes were implanted. Discrete regions of seizure onset and functional cortex were identified, which were used during resection to remove epileptogenic tissue while preserving eloquent areas. There were no hemorrhagic or infectious complications; no patient suffered permanent neurological deficit. The 3-dimensional intraparenchymal grid is useful for identifying the location and extent of epileptic and eloquent brain.

Temperature Control at DBS Electrodes using Heat Sink: Experimentally Validated FEM Model of DBS lead Architecture

PubMed Central

Elwassif, Maged M.; Datta, Abhishek; Rahman, Asif; Bikson, Marom

2012-01-01

There is a growing interest in the use of Deep Brain Stimulation for the treatment of medically refractory movement disorders and other neurological and psychiatric conditions. The extent of temperature increases around DBS electrodes during normal operation (joule heating and increased metabolic activity) or coupling with an external source (e.g. MRI) remains poorly understood and methods to mitigate temperature increases are being actively investigated. We developed a heat transfer finite element method simulation of DBS incorporating the realistic architecture of Medtronic 3389 leads. The temperature changes were analyzed considering different electrode configurations, stimulation protocols, and tissue properties. The heat-transfer model results were then validated using micro-thermocouple measurements during DBS lead stimulation in a saline bath. FEM results indicate that lead design (materials and geometry) may have a central role in controlling temperature rise by conducting heat. We show how modifying lead design can effectively control temperature increases. The robustness of this heat-sink approach over complimentary heat-mitigation technologies follows from several features: 1) it is insensitive to the mechanisms of heating (e.g. nature of magnetic coupling); 2) does not interfere with device efficacy; and 3) can be practically implemented in a broad range of implanted devices without modifying the normal device operations or the implant procedure. PMID:22764359

MRI compatible optrodes for simultaneous LFP and optogenetic fMRI investigation of seizure-like afterdischarges

PubMed Central

Duffy, Ben A; Choy, ManKin; Chuapoco, Miguel R; Madsen, Michael; Lee, Jin Hyung

2017-01-01

In preclinical studies, implanted electrodes can cause severe degradation of MRI images and hence are seldom used for chronic studies employing functional magnetic resonance imaging. In this study, we developed carbon fiber optrodes (optical fiber and electrode hybrid devices), which can be utilised in chronic longitudinal studies aiming to take advantage of emerging optogenetic technologies, and compared them with the more widely used tungsten optrodes. We find that optrodes constructed using small diameter (~130 μm) carbon fiber electrodes cause significantly reduced artifact on functional MRI images compared those made with 50 μm diameter tungsten wire and at the same time the carbon electrodes have lower impedance, which leads to higher quality intracranial LFP recordings. In order to validate this approach, we use these devices to study optogenetically-induced seizure-like afterdischarges in rats sedated with dexmedetomidine and compare these to sub (seizure) threshold stimulations in the same animals. The results indicate that seizure-like afterdischarges involve several extrahippocampal brain regions that are not recruited by subthreshold optogenetic stimulation of the hippocampus at 20 Hz. Subthreshold stimulation led to activation of the entire ipsilateral hippocampus, whereas afterdischarges additionally produced activations in the contralateral hippocampal formation, septum, neocortex, cerebellum, nucleus accumbens, and thalamus. Although we demonstrate just one application, given the ease of fabrication, we anticipate that carbon fiber optrodes could be utilised in a variety of studies that could benefit from longitudinal optogenetic functional magnetic resonance imaging. PMID:26208873

Motion illusion – evidence towards human vestibulo-thalamic projections

PubMed Central

Shaikh, Aasef G.; Straumann, Dominik; Palla, Antonella

2017-01-01

Introduction Contemporary studies speculated that cerebellar network responsible for motion perception projects to the cerebral cortex via vestibulo-thalamus. Here we sought for the physiological properties of vestibulo-thalamic pathway responsible for the motion perception. Methods Healthy subjects and the patient with focal vestibulo-thalamic lacunar stroke spun a hand-held rheostat to approximate the value of perceived angular velocity during whole-body passive earth-vertical axis rotations in yaw plane. Vestibulo-ocular reflex was simultaneously measured with high-resolution search coils (paradigm 1). In primates the vestibulo-thalamic projections remain medial and then dorsomedial to the subthalamus. Therefore the paradigm 2 assessed the effects of high-frequency subthalamic nucleus electrical stimulation through the medial and caudal deep brain stimulation electrode in five subjects with Parkinson’s disease. Results Paradigm 1 discovered directional mismatch of perceived rotation in a patient with vestiblo-thalamic lacune. There was no such mismatch in vestibulo-ocular reflex. Healthy subjects did not have such directional discrepancy of perceived motion. The results confirmed that perceived angular motion is relayed through the thalamus. Stimulation through medial and caudal-most electrode of subthalamic deep brain stimulator in paradigm 2 resulted in perception of rotational motion in the horizontal semicircular canal plane. One patient perceived riding a swing, a complex motion, possibly the combination of vertical canal and otolith derived signals representing pitch and fore-aft motion respectively. Conclusion The results examined physiological properties of the vestibulo-thalamic pathway that passes in proximity to the subthalamic nucleus conducting pure semicircular canal signals and convergent signals from the semicircular canals and the otoliths. PMID:28127679

High-density EEG characterization of brain responses to auditory rhythmic stimuli during wakefulness and NREM sleep.

PubMed

Lustenberger, Caroline; Patel, Yogi A; Alagapan, Sankaraleengam; Page, Jessica M; Price, Betsy; Boyle, Michael R; Fröhlich, Flavio

2018-04-01

Auditory rhythmic sensory stimulation modulates brain oscillations by increasing phase-locking to the temporal structure of the stimuli and by increasing the power of specific frequency bands, resulting in Auditory Steady State Responses (ASSR). The ASSR is altered in different diseases of the central nervous system such as schizophrenia. However, in order to use the ASSR as biological markers for disease states, it needs to be understood how different vigilance states and underlying brain activity affect the ASSR. Here, we compared the effects of auditory rhythmic stimuli on EEG brain activity during wake and NREM sleep, investigated the influence of the presence of dominant sleep rhythms on the ASSR, and delineated the topographical distribution of these modulations. Participants (14 healthy males, 20-33 years) completed on the same day a 60 min nap session and two 30 min wakefulness sessions (before and after the nap). During these sessions, amplitude modulated (AM) white noise auditory stimuli at different frequencies were applied. High-density EEG was continuously recorded and time-frequency analyses were performed to assess ASSR during wakefulness and NREM periods. Our analysis revealed that depending on the electrode location, stimulation frequency applied and window/frequencies analysed the ASSR was significantly modulated by sleep pressure (before and after sleep), vigilance state (wake vs. NREM sleep), and the presence of slow wave activity and sleep spindles. Furthermore, AM stimuli increased spindle activity during NREM sleep but not during wakefulness. Thus, (1) electrode location, sleep history, vigilance state and ongoing brain activity needs to be carefully considered when investigating ASSR and (2) auditory rhythmic stimuli during sleep might represent a powerful tool to boost sleep spindles. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of microscopic modeling of skin in electrical and thermal analysis of transcranial direct current stimulation

NASA Astrophysics Data System (ADS)

Gomez-Tames, Jose; Sugiyama, Yukiya; Laakso, Ilkka; Tanaka, Satoshi; Koyama, Soichiro; Sadato, Norihiro; Hirata, Akimasa

2016-12-01

Transcranial direct current stimulation (tDCS) is a neuromodulation scheme where a small current is delivered to the brain via two electrodes attached to the scalp. The electrode design is an important topic, not only as regards efficacy, but also from a safety perspective, as tDCS may be related to skin lesions that are sometimes observed after stimulation. Previous computational models of tDCS have omitted the effects of microscopic structures in the skin, and the different soak conditions of the electrodes, and model validation has been limited. In this study, multiphysics and multiscale analysis are proposed to demonstrate the importance of microscopic modeling of the skin, in order to clarify the effects of the internal electric field, and to examine temperature elevation around the electrodes. This novel microscopic model of the skin layer took into consideration the effect of saline/water penetration in hair follicles and sweat ducts on the field distribution around the electrodes. The temperature elevation in the skin was then computed by solving the bioheat equation. Also, a multiscale model was introduced to account for macroscopic and microscopic tissues of the head and skin, which was validated by measurement of the head resistance during tDCS. As a result, the electric field in the microscopic model of the skin was less localized when the follicles/ducts were filled with saline instead of hair or tap water. Temperature elevation was also lessened with saline, in comparison with other substances. Saline, which may penetrate the hair follicles and sweat ducts, suppressed the field concentration around the electrodes. For conventional magnitudes of current injection, and a head resistance of less than 10 kΩ, the temperature elevation in the skin when using saline-soaked electrodes was low, less than 0.1 °C, and unlikely to cause adverse thermal effects.

An Integrated Circuit for Simultaneous Extracellular Electrophysiology Recording and Optogenetic Neural Manipulation

PubMed Central

Chen, Chang Hao; McCullagh, Elizabeth A.; Pun, Sio Hang; Mak, Peng Un; Vai, Mang I; Mak, Pui In; Klug, Achim; Lei, Tim C.

2017-01-01

The ability to record and to control action potential firing in neuronal circuits of the brain is critical to understand how the brain functions on the cellular and network levels. Recent development of optogenetic proteins allows direct stimulation or inhibition of action potential firing of neurons upon optical illumination. In this paper, we combined a low-noise and high input impedance (or low input capacitance) neural recording amplifier, and a high current laser/LED driver in a monolithic integrated circuit (IC) for simultaneous neural recording and optogenetic neural control. The low input capacitance of the amplifier (9.7 pF) was achieved through adding a dedicated unity gain input stage optimized for high impedance metal electrodes. The input referred noise of the amplifier was measured to be 4.57 µVrms, which is lower than the estimated thermal noise of the metal electrode. Thus, action potentials originating from a single neuron can be recorded with a signal-to-noise ratio of ~6.6. The LED/laser current driver delivers a maximum current of 330 mA to generate adequate light for optogenetic control. We experimentally tested the functionality of the IC with an anesthetized Mongolian gerbil and recorded auditory stimulated action potentials from the inferior colliculus. Furthermore, we showed that spontaneous firing of 5th (trigeminal) nerve fibers was inhibited using the optogenetic protein Halorhodopsin. A noise model was also derived including the equivalent electronic components of the metal electrode and the high current driver to guide the design. PMID:28221990

Bilateral subthalamic or pallidal stimulation for Parkinson's disease affects neither memory nor executive functions: a consecutive series of 62 patients.

PubMed

Ardouin, C; Pillon, B; Peiffer, E; Bejjani, P; Limousin, P; Damier, P; Arnulf, I; Benabid, A L; Agid, Y; Pollak, P

1999-08-01

There is a renewal of interest in surgical approaches including lesions and deep brain stimulation directed at motor subcorticofrontal loops. Bilateral lesioning presents a far greater risk of adverse effects, especially cognitive impairment. Furthermore, the main advantages of the stimulation procedure over lesioning are adaptability and reversibility of effects. The aim of this study was to assess the influence of bilateral stimulation of the subthalamic nucleus or internal globus pallidus on memory and executive functions in Parkinson's disease. Sixty-two patients were assessed before and after 3 to 6 months of chronic bilateral stimulation of the subthalamic nucleus (n = 49) or internal globus pallidus (n = 13). The neuropsychological tests used were the Mattis Dementia Rating Scale, the Grober and Buschke Verbal Learning Test, the Wisconsin Card Sorting Test, category and literal fluency, graphic and motor series, the Stroop Test, and the Trail Making Test. Mood was evaluated by the Beck Depression Inventory. Only 4 of 25 cognitive variables were affected by deep brain stimulation. Under stimulation, performance improved for Parts A and B of the Trail Making Test, but there was a deterioration in literal and total lexical fluency. There was also a mild but significant improvement in mood. It may therefore be concluded that stimulation of the subthalamic nucleus or internal globus pallidus does not change the overall cognitive performance in Parkinson's disease and does not greatly affect the functioning of subcorticofrontal loops involved in cognition in humans. This relative absence of cognitive impairment in bilateral deep brain stimulation is likely because of the accurate positioning of the electrodes, allowing the effects of stimulation to be confined to sensorimotor circuits.

Vertically aligned carbon nanofiber as nano-neuron interface for monitoring neural function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ericson, Milton Nance; McKnight, Timothy E; Melechko, Anatoli Vasilievich

2012-01-01

Neural chips, which are capable of simultaneous, multi-site neural recording and stimulation, have been used to detect and modulate neural activity for almost 30 years. As a neural interface, neural chips provide dynamic functional information for neural decoding and neural control. By improving sensitivity and spatial resolution, nano-scale electrodes may revolutionize neural detection and modulation at cellular and molecular levels as nano-neuron interfaces. We developed a carbon-nanofiber neural chip with lithographically defined arrays of vertically aligned carbon nanofiber electrodes and demonstrated its capability of both stimulating and monitoring electrophysiological signals from brain tissues in vitro and monitoring dynamic information ofmore » neuroplasticity. This novel nano-neuron interface can potentially serve as a precise, informative, biocompatible, and dual-mode neural interface for monitoring of both neuroelectrical and neurochemical activity at the single cell level and even inside the cell.« less

Distribution and Network of Basal Temporal Language Areas: A Study of the Combination of Electric Cortical Stimulation and Diffusion Tensor Imaging.

PubMed

Enatsu, Rei; Kanno, Aya; Ookawa, Satoshi; Ochi, Satoko; Ishiai, Sumio; Nagamine, Takashi; Mikuni, Nobuhiro

2017-10-01

The basal temporal language area (BTLA) is considered to have several functions in language processing; however, its brain network is still unknown. This study investigated the distribution and networks of the BTLA using a combination of electric cortical stimulation and diffusion tensor imaging (DTI). 10 patients with intractable focal epilepsy who underwent presurgical evaluation with subdural electrodes were enrolled in this study (language dominant side: 6 patients, language nondominant side: 4 patients). Electric stimulation at 50 Hz was applied to the electrodes during Japanese sentence reading, morphograms (kanji) reading, and syllabograms (kana) reading tasks to identify the BTLA. DTI was used to identify the subcortical fibers originating from the BTLA found by electric stimulation. The BTLA was found in 6 patients who underwent implantation of the subdural electrodes in the dominant hemisphere. The BTLA was located anywhere between 20 mm and 56 mm posterior to the temporal tips. In 3 patients, electric stimulation of some or all areas within the BTLA induced disturbance in reading of kanji words only. DTI detected the inferior longitudinal fasciculus (ILF) in all patients and the uncinate fasciculus (UF) in 1 patient, originating from the BTLA. ILF was detected from both kanji-specific areas and kanji-nonspecific areas. This study indicates that the network of the BTLA is a part of a ventral stream and is mainly composed of the ILF, which acts as a critical structure for lexical retrieval. ILF is also associated with the specific processing of kanji words. Copyright © 2017 Elsevier Inc. All rights reserved.

The effects of bilateral stimulation of the subthalamic nucleus on heart rate variability in patients with Parkinson's disease.

PubMed

Liu, Kang-Du; Shan, Din-E; Kuo, Terry B J; Yang, Cheryl C H

2013-07-01

The beneficial effects of subthalamic nucleus deep brain stimulation (STN-DBS) on motor symptoms and quality of life in Parkinson's disease (PD) are well known, but little is known of the effects on autonomic function. Diffusion of current during stimulation of the STN may simultaneously involve the motor and nonmotor, limbic and associative areas of the STN. The aims of this study were to examine whether STN stimulation affects functions of the autonomic nervous system and, if so, to correlate the effects with the active contacts of electrodes in the STN. Eight PD patients with good motor control and quality of sleep after STN-DBS surgery were recruited. All patients had two days of recordings with portable polysomnography (PSG) (first night with stimulation "on" and second night "off"). From the PSG data, the first sleep cycle of each recording night was defined. Heart rate variability (HRV) was analyzed between the same uninterrupted periods of the two sleep nights. In addition, the optimal electrode positions were defined from postoperative MRI studies, and the coordinates of active contacts were confirmed. HRV spectral analysis showed that only low-frequency (LF)/high-frequency (HF) power was significantly activated in the stimulation "on" groups (P = 0.011). There was a significant negative correlation between power change of LF/HF and electrode position lateral to the midcommissural point (ρ = 0.857, P = 0.007) These results demonstrate that STN-DBS can enhance sympathetic regulation; the autonomic response may be due to electrical signals being distributed to limbic components of the STN or descending sympathetic pathways in the zona incerta.

Simultaneous bilateral stereotactic procedure for deep brain stimulation implants: a significant step for reducing operation time.

PubMed

Fonoff, Erich Talamoni; Azevedo, Angelo; Angelos, Jairo Silva Dos; Martinez, Raquel Chacon Ruiz; Navarro, Jessie; Reis, Paul Rodrigo; Sepulveda, Miguel Ernesto San Martin; Cury, Rubens Gisbert; Ghilardi, Maria Gabriela Dos Santos; Teixeira, Manoel Jacobsen; Lopez, William Omar Contreras

2016-07-01

OBJECT Currently, bilateral procedures involve 2 sequential implants in each of the hemispheres. The present report demonstrates the feasibility of simultaneous bilateral procedures during the implantation of deep brain stimulation (DBS) leads. METHODS Fifty-seven patients with movement disorders underwent bilateral DBS implantation in the same study period. The authors compared the time required for the surgical implantation of deep brain electrodes in 2 randomly assigned groups. One group of 28 patients underwent traditional sequential electrode implantation, and the other 29 patients underwent simultaneous bilateral implantation. Clinical outcomes of the patients with Parkinson's disease (PD) who had undergone DBS implantation of the subthalamic nucleus using either of the 2 techniques were compared. RESULTS Overall, a reduction of 38.51% in total operating time for the simultaneous bilateral group (136.4 ± 20.93 minutes) as compared with that for the traditional consecutive approach (220.3 ± 27.58 minutes) was observed. Regarding clinical outcomes in the PD patients who underwent subthalamic nucleus DBS implantation, comparing the preoperative off-medication condition with the off-medication/on-stimulation condition 1 year after the surgery in both procedure groups, there was a mean 47.8% ± 9.5% improvement in the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) score in the simultaneous group, while the sequential group experienced 47.5% ± 15.8% improvement (p = 0.96). Moreover, a marked reduction in the levodopa-equivalent dose from preoperatively to postoperatively was similar in these 2 groups. The simultaneous bilateral procedure presented major advantages over the traditional sequential approach, with a shorter total operating time. CONCLUSIONS A simultaneous stereotactic approach significantly reduces the operation time in bilateral DBS procedures, resulting in decreased microrecording time, contributing to the optimization of functional stereotactic procedures.

Transcranial direct-current stimulation modulates offline visual oscillatory activity: A magnetoencephalography study

PubMed Central

Heinrichs-Graham, Elizabeth; McDermott, Timothy J.; Mills, Mackenzie S.; Coolidge, Nathan M.; Wilson, Tony W.

2017-01-01

Transcranial direct-current stimulation (tDCS) is a noninvasive neuromodulatory method that involves delivering low amplitude, direct current to specific regions of the brain. While a wealth of literature shows changes in behavior and cognition following tDCS administration, the underlying neuronal mechanisms remain largely unknown. Neuroimaging studies have generally used fMRI and shown only limited consensus to date, while the few electrophysiological studies have reported mostly null or counterintuitive findings. The goal of the current investigation was to quantify tDCS-induced alterations in the oscillatory dynamics of visual processing. To this end, we performed either active or sham tDCS using an occipital-frontal electrode configuration, and then recorded magnetoencephalography (MEG) offline during a visual entrainment task. Significant oscillatory responses were imaged in the time-frequency domain using beamforming, and the effects of tDCS on absolute and relative power were assessed. The results indicated significantly increased basal alpha levels in the occipital cortex following anodal tDCS, as well as reduced occipital synchronization at the second harmonic of the stimulus-flicker frequency relative to sham stimulation. In addition, we found reduced power in brain regions near the cathode (e.g., right inferior frontal gyrus) following active tDCS, which was absent in the sham group. Taken together, these results suggest that anodal tDCS of the occipital cortices differentially modulates spontaneous and induced activity, and may interfere with the entrainment of neuronal populations by a visual-flicker stimulus. These findings also demonstrate the importance of electrode configuration on whole-brain dynamics, and highlight the deceptively complicated nature of tDCS in the context of neurophysiology. PMID:28042984

Orientation selective deep brain stimulation

NASA Astrophysics Data System (ADS)

Lehto, Lauri J.; Slopsema, Julia P.; Johnson, Matthew D.; Shatillo, Artem; Teplitzky, Benjamin A.; Utecht, Lynn; Adriany, Gregor; Mangia, Silvia; Sierra, Alejandra; Low, Walter C.; Gröhn, Olli; Michaeli, Shalom

2017-02-01

Objective. Target selectivity of deep brain stimulation (DBS) therapy is critical, as the precise locus and pattern of the stimulation dictates the degree to which desired treatment responses are achieved and adverse side effects are avoided. There is a clear clinical need to improve DBS technology beyond currently available stimulation steering and shaping approaches. We introduce orientation selective neural stimulation as a concept to increase the specificity of target selection in DBS. Approach. This concept, which involves orienting the electric field along an axonal pathway, was tested in the corpus callosum of the rat brain by freely controlling the direction of the electric field on a plane using a three-electrode bundle, and monitoring the response of the neurons using functional magnetic resonance imaging (fMRI). Computational models were developed to further analyze axonal excitability for varied electric field orientation. Main results. Our results demonstrated that the strongest fMRI response was observed when the electric field was oriented parallel to the axons, while almost no response was detected with the perpendicular orientation of the electric field relative to the primary fiber tract. These results were confirmed by computational models of the experimental paradigm quantifying the activation of radially distributed axons while varying the primary direction of the electric field. Significance. The described strategies identify a new course for selective neuromodulation paradigms in DBS based on axonal fiber orientation.

Highly Stable Glassy Carbon Interfaces for Long-Term Neural Stimulation and Low-Noise Recording of Brain Activity

PubMed Central

Vomero, Maria; Castagnola, Elisa; Ciarpella, Francesca; Maggiolini, Emma; Goshi, Noah; Zucchini, Elena; Carli, Stefano; Fadiga, Luciano; Kassegne, Sam; Ricci, Davide

2017-01-01

We report on the superior electrochemical properties, in-vivo performance and long term stability under electrical stimulation of a new electrode material fabricated from lithographically patterned glassy carbon. For a direct comparison with conventional metal electrodes, similar ultra-flexible, micro-electrocorticography (μ-ECoG) arrays with platinum (Pt) or glassy carbon (GC) electrodes were manufactured. The GC microelectrodes have more than 70% wider electrochemical window and 70% higher CTC (charge transfer capacity) than Pt microelectrodes of similar geometry. Moreover, we demonstrate that the GC microelectrodes can withstand at least 5 million pulses at 0.45 mC/cm2 charge density with less than 7.5% impedance change, while the Pt microelectrodes delaminated after 1 million pulses. Additionally, poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) was selectively electrodeposited on both sets of devices to specifically reduce their impedances for smaller diameters (<60 μm). We observed that PEDOT-PSS adhered significantly better to GC than Pt, and allowed drastic reduction of electrode size while maintaining same amount of delivered current. The electrode arrays biocompatibility was demonstrated through in-vitro cell viability experiments, while acute in vivo characterization was performed in rats and showed that GC microelectrode arrays recorded somatosensory evoked potentials (SEP) with an almost twice SNR (signal-to-noise ratio) when compared to the Pt ones. PMID:28084398

General anaesthesia for deep brain stimulator electrode insertion in Parkinson's disease.

PubMed

Sutcliffe, A J; Mitchell, R D; Gan, Y C; Mocroft, A P; Nightingale, P

2011-03-01

This paper compares the use of general and local anaesthetic in patients having deep brain stimulator (DBS) surgery. It is a retrospective case note study of 46 patients treated consecutively with subthalamic nucleus stimulation for Parkinson's disease as practise changed in a Neurosurgical unit. The first 20 patients (LA group) had permanent electrodes placed under local anaesthesia. The remaining 26 patients (GA group) had the entire procedure under general anaesthesia. The groups were similar for age, sex, duration of Parkinson's disease and preoperative levodopa requirement. The clinical results were similar in that within each group, the reduction in levodopa was not only clinically but also statistically significant (p < 0.001 for both, paired t test): for the LA group, the 6-month requirement was 39.4% (29.5-52.6%) of the preoperative requirement and for the GA group, the 6-month requirement was 32.3% (25.2-41.5%) of the preoperative requirement. The reduction in levodopa was maintained at 1 year. Of note, duration of surgery and length of stay were reduced. The mean duration of surgery was 8.2 h (7.8-8.6) for the LA group and 7.5 h (7.2-7.8) for the GA group (p = 0.003). The geometric mean of length of hospital stay was 5.4 days(4.6-6.3) for the LA group and 3.8 days (3.4-4.4) for the GA group (p = 0.001) There was no difference in electrophysiological recording. This study describes benefits in the GA group for the entire procedure of STN DBS. In these samples, there was no difference in the adverse effects seen in patients undergoing deep brain stimulator insertion with general anaesthetic compared with local anaesthetic. The use of general anaesthetic did not detract from the known benefits of surgery.

Electrical stimulation of the lateral habenula produces an inhibitory effect on sucrose self-administration.

PubMed

Friedman, Alexander; Lax, Elad; Dikshtein, Yahav; Abraham, Lital; Flaumenhaft, Yakov; Sudai, Einav; Ben-Tzion, Moshe; Yadid, Gal

2011-01-01

The lateral habenula (LHb) plays a role in prediction of negative reinforcement, punishment and aversive responses. In the current study, we examined the role that the LHb plays in regulation of negative reward responses and aversion. First, we tested the effect of intervention in LHb activity on sucrose reinforcing behavior. An electrode was implanted into the LHb and rats were trained to self-administer sucrose (20%; 16 days) until at least three days of stable performance were achieved (as represented by the number of active lever presses in self-administration cages). Rats subsequently received deep brain stimulation (DBS) of the LHb, which significantly reduced sucrose self-administration levels. In contrast, lesion of the LHb increased sucrose-seeking behavior, as demonstrated by a delayed extinction response to substitution of sucrose with water. Furthermore, in a modified non-rewarding conditioned-place-preference paradigm, DBS of the LHb led to aversion to the context associated with stimulation of this brain region. We postulate that electrical stimulation of the LHb attenuates positive reward-associated reinforcement by natural substances. Copyright © 2010 Elsevier Ltd. All rights reserved.

Polarity-dependent effects of transcranial direct current stimulation in obsessive-compulsive disorder.

PubMed

D'Urso, Giordano; Brunoni, Andre Russowsky; Anastasia, Annalisa; Micillo, Marco; de Bartolomeis, Andrea; Mantovani, Antonio

2016-01-01

About one third of patients with obsessive-compulsive disorder (OCD) fail to experience significant clinical benefit from currently available treatments. Hyperactivity of the presupplementary motor area (pre-SMA) has been detected in OCD patients, but it is not clear whether it is the primary cause or a secondary compensatory mechanism in OCD pathophysiology. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique with polarity-dependent effects on motor cortical excitability. A 33-year-old woman with treatment-resistant OCD received 20 daily consecutive 2 mA/20 min tDCS sessions with the active electrode placed on the pre-SMA, according to the 10-20 EEG system, and the reference electrode on the right deltoid. The first 10 sessions were anodal, while the last 10 were cathodal. Symptoms severity was assessed using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) severity score. In the end of anodal stimulation, OCD symptoms had worsened. Subsequent cathodal stimulation induced a dramatic clinical improvement, which led to an overall 30% reduction in baseline symptoms severity score on the Y-BOCS. Our study supports the hypothesis that pre-SMA hyperfunction might be responsible for OCD symptoms and shows that cathodal inhibitory tDCS over this area might be an option when dealing with treatment-resistant OCD.

Direct measurement of glutamate release in the brain using a dual enzyme-based electrochemical sensor.

PubMed

Hu, Y; Mitchell, K M; Albahadily, F N; Michaelis, E K; Wilson, G S

1994-10-03

The in vivo measurement of the rapid changes in the extracellular concentrations of L-glutamic acid in the mammalian brain during normal neuronal activity or following excessive release due to episodes of anoxia or ischemia has not been possible to this date. Current techniques for the measurement of the release of endogenous glutamate into the extracellular space of the central nervous system are relatively slow and do not measure the actual concentration of free glutamate in the extracellular space. An enzyme-based electrode with rapid response times (about 1 s) and high degree of sensitivity (less than 2 microM) and selectivity for L-glutamic acid is described in this paper. This electrode has both L-glutamate and ascorbate oxidase immobilized on its surface. The latter enzyme removes almost completely any interferences produced by the high levels of extracellular ascorbate present in brain tissue. The response of the electrode to glutamate and other potentially interfering substances was fully characterized in vitro and its selectivity, sensitivity and rapidity in responding to a rise in extracellular glutamate concentrations was also demonstrated in vivo. Placement of the electrode in the dentate gyrus of the hippocampus led to the detection of both KCl-induced release of L-glutamic acid and the release induced by stimulation of the axons in the perforant pathway. The development of this selective, sensitive and rapidly responding glutamate sensor should make it now possible to measure the dynamic events associated with glutamate neurotransmission in the central nervous system.

Brain Tissue Oxygen: In Vivo Monitoring with Carbon Paste Electrodes

PubMed Central

Bolger, Fiachra B.; Lowry, John P.

2005-01-01

In this communication we review selected experiments involving the use of carbon paste electrodes (CPEs) to monitor and measure brain tissue O2 levels in awake freely-moving animals. Simultaneous measurements of rCBF were performed using the H2 clearance technique. Voltammetric techniques used include both differential pulse (O2) and constant potential amperometry (rCBF). Mild hypoxia and hyperoxia produced rapid changes (decrease and increase respectively) in the in vivo O2 signal. Neuronal activation (tail pinch and stimulated grooming) produced similar increases in both O2and rCBF indicating that CPE O2currents provide an index of increases in rCBF when such increases exceed O2 utilization. Saline injection produced a transient increase in the O2 signal while chloral hydrate produced slower more long-lasting changes that accompanied the behavioral changes associated with anaesthesia. Acetazolamide increased O2 levels through an increase in rCBF.

Functional and Histological Effects of Chronic Neural Electrode Implantation.

PubMed

Sahyouni, Ronald; Chang, David T; Moshtaghi, Omid; Mahmoodi, Amin; Djalilian, Hamid R; Lin, Harrison W

2017-04-01

Permanent injury to the cranial nerves can often result in a substantial reduction in quality of life. Novel and innovative interventions can help restore form and function in nerve paralysis, with bioelectric interfaces among the more promising of these approaches. The foreign body response is an important consideration for any bioelectric device as it influences the function and effectiveness of the implant. The purpose of this review is to describe tissue and functional effects of chronic neural implantation among the different categories of neural implants and highlight advances in peripheral and cranial nerve stimulation. Data Sources : PubMed, IEEE, and Web of Science literature search. Review Methods : A review of the current literature was conducted to examine functional and histologic effects of bioelectric interfaces for neural implants. Bioelectric devices can be characterized as intraneural, epineural, perineural, intranuclear, or cortical depending on their placement relative to nerves and neuronal cell bodies. Such devices include nerve-specific stimulators, neuroprosthetics, brainstem implants, and deep brain stimulators. Regardless of electrode location and interface type, acute and chronic histological, macroscopic and functional changes can occur as a result of both passive and active tissue responses to the bioelectric implant. A variety of chronically implantable electrodes have been developed to treat disorders of the peripheral and cranial nerves, to varying degrees of efficacy. Consideration and mitigation of detrimental effects at the neural interface with further optimization of functional nerve stimulation will facilitate the development of these technologies and translation to the clinic. 3.

Transcranial direct current stimulation improves isometric time to exhaustion of the knee extensors.

PubMed

Angius, L; Pageaux, B; Hopker, J; Marcora, S M; Mauger, A R

2016-12-17

Transcranial direct current stimulation (tDCS) can increase cortical excitability of a targeted brain area, which may affect endurance exercise performance. However, optimal electrode placement for tDCS remains unclear. We tested the effect of two different tDCS electrode montages for improving exercise performance. Nine subjects underwent a control (CON), placebo (SHAM) and two different tDCS montage sessions in a randomized design. In one tDCS session, the anodal electrode was placed over the left motor cortex and the cathodal on contralateral forehead (HEAD), while for the other montage the anodal electrode was placed over the left motor cortex and cathodal electrode above the shoulder (SHOULDER). tDCS was delivered for 10min at 2.0mA, after which participants performed an isometric time to exhaustion (TTE) test of the right knee extensors. Peripheral and central neuromuscular parameters were assessed at baseline, after tDCS application and after TTE. Heart rate (HR), ratings of perceived exertion (RPE), and leg muscle exercise-induced muscle pain (PAIN) were monitored during the TTE. TTE was longer and RPE lower in the SHOULDER condition (P<0.05). Central and peripheral parameters, and HR and PAIN did not present any differences between conditions after tDCS stimulation (P>0.05). In all conditions maximal voluntary contraction (MVC) significantly decreased after the TTE (P<0.05) while motor-evoked potential area (MEP) increased after TTE (P<0.05). These findings demonstrate that SHOULDER montage is more effective than HEAD montage to improve endurance performance, likely through avoiding the negative effects of the cathode on excitability. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Electrical stimulation causes rapid changes in electrode impedance of cell-covered electrodes

NASA Astrophysics Data System (ADS)

Newbold, Carrie; Richardson, Rachael; Millard, Rodney; Seligman, Peter; Cowan, Robert; Shepherd, Robert

2011-06-01

Animal and clinical observations of a reduction in electrode impedance following electrical stimulation encouraged the development of an in vitro model of the electrode-tissue interface. This model was used previously to show an increase in impedance with cell and protein cover over electrodes. In this paper, the model was used to assess the changes in electrode impedance and cell cover following application of a charge-balanced biphasic current pulse train. Following stimulation, a large and rapid drop in total impedance (Zt) and access resistance (Ra) occurred. The magnitude of this impedance change was dependent on the current amplitude used, with a linear relationship determined between Ra and the resulting cell cover over the electrodes. The changes in impedance due to stimulation were shown to be transitory, with impedance returning to pre-stimulation levels several hours after cessation of stimulation. A loss of cells over the electrode surface was observed immediately after stimulation, suggesting that the level of stimulation applied was creating localized changes to cell adhesion. Similar changes in electrode impedance were observed for in vivo and in vitro work, thus helping to verify the in vitro model, although the underlying mechanisms may differ. A change in the porosity of the cellular layer was proposed to explain the alterations in electrode impedance in vitro. These in vitro studies provide insight into the possible mechanisms occurring at the electrode-tissue interface in association with electrical stimulation.

Fully Implantable Deep Brain Stimulation System with Wireless Power Transmission for Long-term Use in Rodent Models of Parkinson's Disease.

PubMed

Heo, Man Seung; Moon, Hyun Seok; Kim, Hee Chan; Park, Hyung Woo; Lim, Young Hoon; Paek, Sun Ha

2015-03-01

The purpose of this study to develop new deep-brain stimulation system for long-term use in animals, in order to develop a variety of neural prostheses. Our system has two distinguished features, which are the fully implanted system having wearable wireless power transfer and ability to change the parameter of stimulus parameter. It is useful for obtaining a variety of data from a long-term experiment. To validate our system, we performed pre-clinical test in Parkinson's disease-rat models for 4 weeks. Through the in vivo test, we observed the possibility of not only long-term implantation and stability, but also free movement of animals. We confirmed that the electrical stimulation neither caused any side effect nor damaged the electrodes. We proved possibility of our system to conduct the long-term pre-clinical test in variety of parameter, which is available for development of neural prostheses.

The Effect of a Transcranial Channel as a Skull/Brain Interface in High-Definition Transcranial Direct Current Stimulation-A Computational Study.

PubMed

Seo, Hyeon; Kim, Hyoung-Ihl; Jun, Sung Chan

2017-01-13

A transcranial channel is an interface between the skull and brain; it consists of a biocompatible and highly conductive material that helps convey the current induced by transcranial direct current stimulation (tDCS) to the target area. However, it has been proposed only conceptually, and there has been no concrete study of its efficacy. In this work, we conducted a computational investigation of this conceptual transcranial model with high-definition tDCS, inducing focalized neuromodulation to determine whether inclusion of a transcranial channel performs effectively. To do so, we constructed an anatomically realistic head model and compartmental pyramidal neuronal models. We analyzed membrane polarization by extracellular stimulation and found that the inclusion of a transcranial channel induced polarization at the target area 11 times greater than conventional HD-tDCS without the transcranial channel. Furthermore, the stimulation effect of the transcranial channel persisted up to approximately 80%, even when the stimulus electrodes were displaced approximately 5 mm from the target area. We investigated the efficacy of the transcranial channel and found that greatly improved stimulation intensity and focality may be achieved. Thus, the use of these channels may be promising for clinical treatment.

Targeting the brain: considerations in 332 consecutive patients treated by deep brain stimulation (DBS) for severe neurological diseases.

PubMed

Franzini, Angelo; Cordella, Roberto; Messina, Giuseppe; Marras, Carlo Efisio; Romito, Luigi Michele; Albanese, Alberto; Rizzi, Michele; Nardocci, Nardo; Zorzi, Giovanna; Zekaj, Edvin; Villani, Flavio; Leone, Massimo; Gambini, Orsola; Broggi, Giovanni

2012-12-01

Deep brain stimulation (DBS) extends the treatment of some severe neurological diseases beyond pharmacological and conservative therapy. Our experience extends the field of DBS beyond the treatment of Parkinson disease and dystonia, including several other diseases such as cluster headache and disruptive behavior. Since 1993, at the Istituto Nazionale Neurologico "Carlo Besta" in Milan, 580 deep brain electrodes were implanted in 332 patients. The DBS targets include Stn, GPi, Voa, Vop, Vim, CM-pf, pHyp, cZi, Nacc, IC, PPN, and Brodmann areas 24 and 25. Three hundred patients are still available for follow-up and therapeutic considerations. DBS gave a new therapeutic chance to these patients affected by severe neurological diseases and in some cases controlled life-threatening pathological conditions, which would otherwise result in the death of the patient such as in status dystonicus, status epilepticus and post-stroke hemiballismus. The balance of DBS in severe neurological disease is strongly positive even if further investigations and studies are needed to search for new applications and refine the selection criteria for the actual indications.

Simultaneous transcranial magnetic stimulation and single neuron recording in alert non-human primates

PubMed Central

Mueller, Jerel K.; Grigsby, Erinn M.; Prevosto, Vincent; Petraglia, Frank W.; Rao, Hrishikesh; Deng, Zhi-De; Peterchev, Angel V.; Sommer, Marc A.; Egner, Tobias; Platt, Michael L.; Grill, Warren M.

2014-01-01

Transcranial magnetic stimulation (TMS) is a widely used, noninvasive method for stimulating nervous tissue, yet its mechanisms of effect are poorly understood. Here we report novel methods for studying the influence of TMS on single neurons in the brain of alert non-human primates. We designed a TMS coil that focuses its effect near the tip of a recording electrode and recording electronics that enable direct acquisition of neuronal signals at the site of peak stimulus strength minimally perturbed by stimulation artifact in intact, awake monkeys (Macaca mulatta). We recorded action potentials within ~1 ms after 0.4 ms TMS pulses and observed changes in activity that differed significantly for active stimulation as compared to sham stimulation. The methodology is compatible with standard equipment in primate laboratories, allowing for easy implementation. Application of these new tools will facilitate the refinement of next generation TMS devices, experiments, and treatment protocols. PMID:24974797

Considering the influence of stimulation parameters on the effect of conventional and high-definition transcranial direct current stimulation.

PubMed

To, Wing Ting; Hart, John; De Ridder, Dirk; Vanneste, Sven

2016-01-01

Recently, techniques to non-invasively modulate specific brain areas gained popularity in the form of transcranial direct current stimulation (tDCS) and high-definition transcranial direct current stimulation. These non-invasive techniques have already shown promising outcomes in various studies with healthy subjects as well as patient populations. Despite widespread dissemination of tDCS, there remain significant unknowns about the influence of a diverse number of tDCS parameters (e.g. polarity, size, position of electrodes & duration of stimulation) in inducing neurophysiological and behavioral effects. This article explores both techniques starting with the history of tDCS, to the differences between conventional tDCS and high-definition transcranial direct current stimulation, the underlying physiological mechanism, the (in)direct effects, the applications of tDCS with varying parameters, the efficacy, the safety issues and the opportunities for future research.

Distributed stimulation increases force elicited with functional electrical stimulation

NASA Astrophysics Data System (ADS)

Buckmire, Alie J.; Lockwood, Danielle R.; Doane, Cynthia J.; Fuglevand, Andrew J.

2018-04-01

Objective. The maximum muscle forces that can be evoked using functional electrical stimulation (FES) are relatively modest. The reason for this weakness is not fully understood but could be partly related to the widespread distribution of motor nerve branches within muscle. As such, a single stimulating electrode (as is conventionally used) may be incapable of activating the entire array of motor axons supplying a muscle. Therefore, the objective of this study was to determine whether stimulating a muscle with more than one source of current could boost force above that achievable with a single source. Approach. We compared the maximum isometric forces that could be evoked in the anterior deltoid of anesthetized monkeys using one or two intramuscular electrodes. We also evaluated whether temporally interleaved stimulation between two electrodes might reduce fatigue during prolonged activity compared to synchronized stimulation through two electrodes. Main results. We found that dual electrode stimulation consistently produced greater force (~50% greater on average) than maximal stimulation with single electrodes. No differences, however, were found in the fatigue responses using interleaved versus synchronized stimulation. Significance. It seems reasonable to consider using multi-electrode stimulation to augment the force-generating capacity of muscles and thereby increase the utility of FES systems.

A simple method for EEG guided transcranial electrical stimulation without models.

PubMed

Cancelli, Andrea; Cottone, Carlo; Tecchio, Franca; Truong, Dennis Q; Dmochowski, Jacek; Bikson, Marom

2016-06-01

There is longstanding interest in using EEG measurements to inform transcranial Electrical Stimulation (tES) but adoption is lacking because users need a simple and adaptable recipe. The conventional approach is to use anatomical head-models for both source localization (the EEG inverse problem) and current flow modeling (the tES forward model), but this approach is computationally demanding, requires an anatomical MRI, and strict assumptions about the target brain regions. We evaluate techniques whereby tES dose is derived from EEG without the need for an anatomical head model, target assumptions, difficult case-by-case conjecture, or many stimulation electrodes. We developed a simple two-step approach to EEG-guided tES that based on the topography of the EEG: (1) selects locations to be used for stimulation; (2) determines current applied to each electrode. Each step is performed based solely on the EEG with no need for head models or source localization. Cortical dipoles represent idealized brain targets. EEG-guided tES strategies are verified using a finite element method simulation of the EEG generated by a dipole, oriented either tangential or radial to the scalp surface, and then simulating the tES-generated electric field produced by each model-free technique. These model-free approaches are compared to a 'gold standard' numerically optimized dose of tES that assumes perfect understanding of the dipole location and head anatomy. We vary the number of electrodes from a few to over three hundred, with focality or intensity as optimization criterion. Model-free approaches evaluated include (1) voltage-to-voltage, (2) voltage-to-current; (3) Laplacian; and two Ad-Hoc techniques (4) dipole sink-to-sink; and (5) sink to concentric. Our results demonstrate that simple ad hoc approaches can achieve reasonable targeting for the case of a cortical dipole, remarkably with only 2-8 electrodes and no need for a model of the head. Our approach is verified directly only for a theoretically localized source, but may be potentially applied to an arbitrary EEG topography. For its simplicity and linearity, our recipe for model-free EEG guided tES lends itself to broad adoption and can be applied to static (tDCS), time-variant (e.g., tACS, tRNS, tPCS), or closed-loop tES.

A simple method for EEG guided transcranial electrical stimulation without models

NASA Astrophysics Data System (ADS)

Cancelli, Andrea; Cottone, Carlo; Tecchio, Franca; Truong, Dennis Q.; Dmochowski, Jacek; Bikson, Marom

2016-06-01

Objective. There is longstanding interest in using EEG measurements to inform transcranial Electrical Stimulation (tES) but adoption is lacking because users need a simple and adaptable recipe. The conventional approach is to use anatomical head-models for both source localization (the EEG inverse problem) and current flow modeling (the tES forward model), but this approach is computationally demanding, requires an anatomical MRI, and strict assumptions about the target brain regions. We evaluate techniques whereby tES dose is derived from EEG without the need for an anatomical head model, target assumptions, difficult case-by-case conjecture, or many stimulation electrodes. Approach. We developed a simple two-step approach to EEG-guided tES that based on the topography of the EEG: (1) selects locations to be used for stimulation; (2) determines current applied to each electrode. Each step is performed based solely on the EEG with no need for head models or source localization. Cortical dipoles represent idealized brain targets. EEG-guided tES strategies are verified using a finite element method simulation of the EEG generated by a dipole, oriented either tangential or radial to the scalp surface, and then simulating the tES-generated electric field produced by each model-free technique. These model-free approaches are compared to a ‘gold standard’ numerically optimized dose of tES that assumes perfect understanding of the dipole location and head anatomy. We vary the number of electrodes from a few to over three hundred, with focality or intensity as optimization criterion. Main results. Model-free approaches evaluated include (1) voltage-to-voltage, (2) voltage-to-current; (3) Laplacian; and two Ad-Hoc techniques (4) dipole sink-to-sink; and (5) sink to concentric. Our results demonstrate that simple ad hoc approaches can achieve reasonable targeting for the case of a cortical dipole, remarkably with only 2-8 electrodes and no need for a model of the head. Significance. Our approach is verified directly only for a theoretically localized source, but may be potentially applied to an arbitrary EEG topography. For its simplicity and linearity, our recipe for model-free EEG guided tES lends itself to broad adoption and can be applied to static (tDCS), time-variant (e.g., tACS, tRNS, tPCS), or closed-loop tES.

Transcranial focal stimulation via concentric ring electrodes reduced power of pentylenetetrazole-induced seizure activity in rat electroencephalogram.

PubMed

Makeyev, Oleksandr; Liu, Xiang; Koka, Kanthaiah; Kay, Steven M; Besio, Walter G

2011-01-01

As epilepsy affects approximately one percent of the world population, electrical stimulation of the brain has recently shown potential for additive seizure control therapy. In this study we applied noninvasive transcranial focal stimulation (TFS) via concentric ring electrodes on the scalp of rats after inducing seizures with pentylenetetrazole (PTZ) to assess the effect of TFS on the electrographic activity. Grand average power spectral densities were calculated to compare different stages of seizure development. They showed a significant difference between the TFS treated group and the control group. In case of the TFS treated group, after TFS, the power spectral density was reduced further towards a pre-seizure "baseline" than it was for the control group. The difference is the most drastic in delta, theta and alpha frequency bands. Application of general likelihood ratio test showed that TFS significantly (p<0.001) reduced the power of electrographic seizure activity in the TFS treated group compared to controls in more than 86% of the cases. These results suggest that TFS may have an anticonvulsant effect.

Neurotechnology: a new approach for treating brain disorders.

PubMed

Robson, John A; Davenport, R John

2014-05-01

Advances in neuroscience, engineering and computer technologies are creating opportunities to connect the brain directly to devices to treat a variety of disorders, both neurological and psychiatric. They are opening a new field of neuroscience called "neurotechnology." This article reviews efforts in this area that are ongoing at Brown University and the hospitals affiliated with Brown's Alpert Medical School. Two general approaches are being used. One uses advanced electrodes to "sense" the activity of many individual neurons in the cerebral cortex and then use that activity for therapeutic purposes. The other uses various types of devices to stimulate specific networks in the brain in order to restore normal function and alleviate symptoms.

3D finite element modeling of epiretinal stimulation: Impact of prosthetic electrode size and distance from the retina.

PubMed

Sui, Xiaohong; Huang, Yu; Feng, Fuchen; Huang, Chenhui; Chan, Leanne Lai Hang; Wang, Guoxing

2015-05-01

A novel 3-dimensional (3D) finite element model was established to systematically investigate the impact of the diameter (Φ) of disc electrodes and the electrode-to-retina distance on the effectiveness of stimulation. The 3D finite element model was established based on a disc platinum stimulating electrode and a 6-layered retinal structure. The ground electrode was placed in the extraocular space in direct attachment with sclera and treated as a distant return electrode. An established criterion of electric-field strength of 1000 Vm-1 was adopted as the activation threshold for RGCs. The threshold current (TC) increased linearly with increasing Φ and electrode-to-retina distance and remained almost unchanged with further increases in diameter. However, the threshold charge density (TCD) increased dramatically with decreasing electrode diameter. TCD exceeded the electrode safety limit for an electrode diameter of 50 µm at an electrode-to-retina distance of 50 to 200 μm. The electric field distributions illustrated that smaller electrode diameters and shorter electrode-to-retina distances were preferred due to more localized excitation of RGC area under stimulation of different threshold currents in terms of varied electrode size and electrode-to-retina distances. Under the condition of same-amplitude current stimulation, a large electrode exhibited an improved potential spatial selectivity at large electrode-to-retina distances. Modeling results were consistent with those reported in animal electrophysiological experiments and clinical trials, validating the 3D finite element model of epiretinal stimulation. The computational model proved to be useful in optimizing the design of an epiretinal stimulating electrode for prosthesis.

Lightning may pose a danger to patients receiving deep brain stimulation: case report.

PubMed

Prezelj, Neža; Trošt, Maja; Georgiev, Dejan; Flisar, Dušan

2018-05-01

Deep brain stimulation (DBS) is an established treatment option for advanced stages of Parkinson's disease and other movement disorders. It is known that DBS is susceptible to strong electromagnetic fields (EMFs) that can be generated by various electrical devices at work, home, and in medical environments. EMFs can interfere with the proper functioning of implantable pulse generators (IPGs). Very strong EMFs can generate induction currents in implanted electrodes and even damage the brain. Manufacturers of DBS devices have issued a list of warnings on how to avoid this danger. Strong EMFs can result from natural forces as well. The authors present the case of a 66-year-old woman who was being treated with a rechargeable DBS system for neck dystonia when her apartment was struck by lightning. Domestic electronic devices that were operating during the event were burned and destroyed. The woman's IPG switched off but remained undamaged, and she suffered no neurological consequences.

Design of electrical stimulation bioreactors for cardiac tissue engineering.

PubMed

Tandon, N; Marsano, A; Cannizzaro, C; Voldman, J; Vunjak-Novakovic, G

2008-01-01

Electrical stimulation has been shown to improve functional assembly of cardiomyocytes in vitro for cardiac tissue engineering. Carbon electrodes were found in past studies to have the best current injection characteristics. The goal of this study was to develop rational experimental design principles for the electrodes and stimulation regime, in particular electrode configuration, electrode ageing, and stimulation amplitude. Carbon rod electrodes were compared via electrochemical impedance spectroscopy (EIS) and we identified a safety range of 0 to 8 V/cm by comparing excitation thresholds and maximum capture rates for neonatal rat cardiomyocytes cultured with electrical stimulation. We conclude with recommendations for studies involving carbon electrodes for cardiac tissue engineering.

The Effect of Uni- and Bilateral Thalamic Deep Brain Stimulation on Speech in Patients With Essential Tremor: Acoustics and Intelligibility.

PubMed

Becker, Johannes; Barbe, Michael T; Hartinger, Mariam; Dembek, Till A; Pochmann, Jil; Wirths, Jochen; Allert, Niels; Mücke, Doris; Hermes, Anne; Meister, Ingo G; Visser-Vandewalle, Veerle; Grice, Martine; Timmermann, Lars

2017-04-01

Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) is performed to suppress medically-resistant essential tremor (ET). However, stimulation induced dysarthria (SID) is a common side effect, limiting the extent to which tremor can be suppressed. To date, the exact pathogenesis of SID in VIM-DBS treated ET patients is unknown. We investigate the effect of inactivated, uni- and bilateral VIM-DBS on speech production in patients with ET. We employ acoustic measures, tempo, and intelligibility ratings and patient's self-estimated speech to quantify SID, with a focus on comparing bilateral to unilateral stimulation effects and the effect of electrode position on speech. Sixteen German ET patients participated in this study. Each patient was acoustically recorded with DBS-off, unilateral-right-hemispheric-DBS-on, unilateral-left-hemispheric-DBS-on, and bilateral-DBS-on during an oral diadochokinesis task and a read German standard text. To capture the extent of speech impairment, we measured syllable duration and intensity ratio during the DDK task. Naïve listeners rated speech tempo and speech intelligibility of the read text on a 5-point-scale. Patients had to rate their "ability to speak". We found an effect of bilateral compared to unilateral and inactivated stimulation on syllable durations and intensity ratio, as well as on external intelligibility ratings and patients' VAS scores. Additionally, VAS scores are associated with more laterally located active contacts. For speech ratings, we found an effect of syllable duration such that tempo and intelligibility was rated worse for speakers exhibiting greater syllable durations. Our data confirms that SID is more pronounced under bilateral compared to unilateral stimulation. Laterally located electrodes are associated with more severe SID according to patient's self-ratings. We can confirm the relation between diadochokinetic rate and SID in that listener's tempo and intelligibility ratings can be predicted by measured syllable durations from DDK tasks. © 2017 International Neuromodulation Society.

Spatial channel interactions in cochlear implants

NASA Astrophysics Data System (ADS)

Tang, Qing; Benítez, Raul; Zeng, Fan-Gang

2011-08-01

The modern multi-channel cochlear implant is widely considered to be the most successful neural prosthesis owing to its ability to restore partial hearing to post-lingually deafened adults and to allow essentially normal language development in pre-lingually deafened children. However, the implant performance varies greatly in individuals and is still limited in background noise, tonal language understanding, and music perception. One main cause for the individual variability and the limited performance in cochlear implants is spatial channel interaction from the stimulating electrodes to the auditory nerve and brain. Here we systematically examined spatial channel interactions at the physical, physiological, and perceptual levels in the same five modern cochlear implant subjects. The physical interaction was examined using an electric field imaging technique, which measured the voltage distribution as a function of the electrode position in the cochlea in response to the stimulation of a single electrode. The physiological interaction was examined by recording electrically evoked compound action potentials as a function of the electrode position in response to the stimulation of the same single electrode position. The perceptual interactions were characterized by changes in detection threshold as well as loudness summation in response to in-phase or out-of-phase dual-electrode stimulation. To minimize potentially confounding effects of temporal factors on spatial channel interactions, stimulus rates were limited to 100 Hz or less in all measurements. Several quantitative channel interaction indexes were developed to define and compare the width, slope and symmetry of the spatial excitation patterns derived from these physical, physiological and perceptual measures. The electric field imaging data revealed a broad but uniformly asymmetrical intracochlear electric field pattern, with the apical side producing a wider half-width and shallower slope than the basal side. In contrast, the evoked compound action potential and perceptual channel interaction data showed much greater individual variability. It is likely that actual reduction in neural and higher level interactions, instead of simple sharpening of the electric current field, would be the key to predicting and hopefully improving the variable cochlear implant performance. The present results are obtained with auditory prostheses but can be applied to other neural prostheses, in which independent spatial channels, rather than a high stimulation rate, are critical to their performance.

Robotic Stereotaxy in Cranial Neurosurgery: A Qualitative Systematic Review.

PubMed

Fomenko, Anton; Serletis, Demitre

2017-12-14

Modern-day stereotactic techniques have evolved to tackle the neurosurgical challenge of accurately and reproducibly accessing specific brain targets. Neurosurgical advances have been made in synergy with sophisticated technological developments and engineering innovations such as automated robotic platforms. Robotic systems offer a unique combination of dexterity, durability, indefatigability, and precision. To perform a systematic review of robotic integration for cranial stereotactic guidance in neurosurgery. Specifically, we comprehensively analyze the strengths and weaknesses of a spectrum of robotic technologies, past and present, including details pertaining to each system's kinematic specifications and targeting accuracy profiles. Eligible articles on human clinical applications of cranial robotic-guided stereotactic systems between 1985 and 2017 were extracted from several electronic databases, with a focus on stereotactic biopsy procedures, stereoelectroencephalography, and deep brain stimulation electrode insertion. Cranial robotic stereotactic systems feature serial or parallel architectures with 4 to 7 degrees of freedom, and frame-based or frameless registration. Indications for robotic assistance are diversifying, and include stereotactic biopsy, deep brain stimulation and stereoelectroencephalography electrode placement, ventriculostomy, and ablation procedures. Complication rates are low, and mainly consist of hemorrhage. Newer systems benefit from increasing targeting accuracy, intraoperative imaging ability, improved safety profiles, and reduced operating times. We highlight emerging future directions pertaining to the integration of robotic technologies into future neurosurgical procedures. Notably, a trend toward miniaturization, cost-effectiveness, frameless registration, and increasing safety and accuracy characterize successful stereotactic robotic technologies. Copyright © 2017 by the Congress of Neurological Surgeons

Nanomaterial-Enabled Neural Stimulation

PubMed Central

Wang, Yongchen; Guo, Liang

2016-01-01

Neural stimulation is a critical technique in treating neurological diseases and investigating brain functions. Traditional electrical stimulation uses electrodes to directly create intervening electric fields in the immediate vicinity of neural tissues. Second-generation stimulation techniques directly use light, magnetic fields or ultrasound in a non-contact manner. An emerging generation of non- or minimally invasive neural stimulation techniques is enabled by nanotechnology to achieve a high spatial resolution and cell-type specificity. In these techniques, a nanomaterial converts a remotely transmitted primary stimulus such as a light, magnetic or ultrasonic signal to a localized secondary stimulus such as an electric field or heat to stimulate neurons. The ease of surface modification and bio-conjugation of nanomaterials facilitates cell-type-specific targeting, designated placement and highly localized membrane activation. This review focuses on nanomaterial-enabled neural stimulation techniques primarily involving opto-electric, opto-thermal, magneto-electric, magneto-thermal and acousto-electric transduction mechanisms. Stimulation techniques based on other possible transduction schemes and general consideration for these emerging neurotechnologies are also discussed. PMID:27013938

Design of Electrical Stimulation Bioreactors for Cardiac Tissue Engineering

PubMed Central

Tandon, N.; Marsano, A.; Cannizzaro, C.; Voldman, J.; Vunjak-Novakovic, G.

2009-01-01

Electrical stimulation has been shown to improve functional assembly of cardiomyocytes in vitro for cardiac tissue engineering. Carbon electrodes were found in past studies to have the best current injection characteristics. The goal of this study was to develop rational experimental design principles for the electrodes and stimulation regime, in particular electrode configuration, electrode ageing, and stimulation amplitude. Carbon rod electrodes were compared via electrochemical impedance spectroscopy (EIS) and we identified a safety range of 0 to 8 V/cm by comparing excitation thresholds and maximum capture rates for neonatal rat cardiomyocytes cultured with electrical stimulation. We conclude with recommendations for studies involving carbon electrodes for cardiac tissue engineering. PMID:19163486

Temperature control at DBS electrodes using a heat sink: experimentally validated FEM model of DBS lead architecture.

PubMed

Elwassif, Maged M; Datta, Abhishek; Rahman, Asif; Bikson, Marom

2012-08-01

There is a growing interest in the use of deep brain stimulation (DBS) for the treatment of medically refractory movement disorders and other neurological and psychiatric conditions. The extent of temperature increases around DBS electrodes during normal operation (joule heating and increased metabolic activity) or coupling with an external source (e.g. magnetic resonance imaging) remains poorly understood and methods to mitigate temperature increases are being actively investigated. We developed a heat transfer finite element method (FEM) simulation of DBS incorporating the realistic architecture of Medtronic 3389 leads. The temperature changes were analyzed considering different electrode configurations, stimulation protocols and tissue properties. The heat-transfer model results were then validated using micro-thermocouple measurements during DBS lead stimulation in a saline bath. FEM results indicate that lead design (materials and geometry) may have a central role in controlling temperature rise by conducting heat. We show how modifying lead design can effectively control temperature increases. The robustness of this heat-sink approach over complimentary heat-mitigation technologies follows from several features: (1) it is insensitive to the mechanisms of heating (e.g. nature of magnetic coupling); (2) it does not interfere with device efficacy; and (3) can be practically implemented in a broad range of implanted devices without modifying the normal device operations or the implant procedure.

Temperature control at DBS electrodes using a heat sink: experimentally validated FEM model of DBS lead architecture

NASA Astrophysics Data System (ADS)

Elwassif, Maged M.; Datta, Abhishek; Rahman, Asif; Bikson, Marom

2012-08-01

There is a growing interest in the use of deep brain stimulation (DBS) for the treatment of medically refractory movement disorders and other neurological and psychiatric conditions. The extent of temperature increases around DBS electrodes during normal operation (joule heating and increased metabolic activity) or coupling with an external source (e.g. magnetic resonance imaging) remains poorly understood and methods to mitigate temperature increases are being actively investigated. We developed a heat transfer finite element method (FEM) simulation of DBS incorporating the realistic architecture of Medtronic 3389 leads. The temperature changes were analyzed considering different electrode configurations, stimulation protocols and tissue properties. The heat-transfer model results were then validated using micro-thermocouple measurements during DBS lead stimulation in a saline bath. FEM results indicate that lead design (materials and geometry) may have a central role in controlling temperature rise by conducting heat. We show how modifying lead design can effectively control temperature increases. The robustness of this heat-sink approach over complimentary heat-mitigation technologies follows from several features: (1) it is insensitive to the mechanisms of heating (e.g. nature of magnetic coupling); (2) it does not interfere with device efficacy; and (3) can be practically implemented in a broad range of implanted devices without modifying the normal device operations or the implant procedure.

Central Visual Prosthesis With Interface at the Lateral Geniculate Nucleus

DTIC Science & Technology

2017-07-01

burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching...currently used in the field to implant Deep Brain Stimulation electrodes. Page 4 We thus limited ourselves to using a ‘4 French’ size split sheath...this program. At this time , several approaches for realizing the complete system have been evaluated. Initially, a very simple mechanical mockup

PEDOT-CNT coated electrodes stimulate retinal neurons at low voltage amplitudes and low charge densities

NASA Astrophysics Data System (ADS)

Samba, R.; Herrmann, T.; Zeck, G.

2015-02-01

Objective. The aim of this study was to compare two different microelectrode materials—the conductive polymer composite poly-3,4-ethylenedioxythiophene (PEDOT)-carbon nanotube(CNT) and titanium nitride (TiN)—at activating spikes in retinal ganglion cells in whole mount rat retina through stimulation of the local retinal network. Stimulation efficacy of the microelectrodes was analyzed by comparing voltage, current and transferred charge at stimulation threshold. Approach. Retinal ganglion cell spikes were recorded by a central electrode (30 μm diameter) in the planar grid of an electrode array. Extracellular stimulation (monophasic, cathodic, 0.1-1.0 ms) of the retinal network was performed using constant voltage pulses applied to the eight surrounding electrodes. The stimulation electrodes were equally spaced on the four sides of a square (400 × 400 μm). Threshold voltage was determined as the pulse amplitude required to evoke network-mediated ganglion cell spiking in a defined post stimulus time window in 50% of identical stimulus repetitions. For the two electrode materials threshold voltage, transferred charge at threshold, maximum current and the residual current at the end of the pulse were compared. Main results. Stimulation of retinal interneurons using PEDOT-CNT electrodes is achieved with lower stimulation voltage and requires lower charge transfer as compared to TiN. The key parameter for effective stimulation is a constant current over at least 0.5 ms, which is obtained by PEDOT-CNT electrodes at lower stimulation voltage due to its faradaic charge transfer mechanism. Significance. In neuroprosthetic implants, PEDOT-CNT may allow for smaller electrodes, effective stimulation in a safe voltage regime and lower energy-consumption. Our study also indicates, that the charge transferred at threshold or the charge injection capacity per se does not determine stimulation efficacy.

Chips of Hope: Neuro-Electronic Hybrids for Brain Repair

NASA Astrophysics Data System (ADS)

Ben-Jacob, Eshel

2010-03-01

The field of Neuro-Electronic Hybrids kicked off 30 years ago when researchers in the US first tweaked the technology of recording and stimulation of networks of live neurons grown in a Petri dish and interfaced with a computer via an array of electrodes. Since then, many researchers have searched for ways to imprint in neural networks new ``memories" without erasing old ones. I will describe our new generation of Neuro-Electronic Hybrids and how we succeeded to turn them into the first learning Neurochips - memory and information processing chips made of live neurons. To imprint multiple memories in our new chip we used chemical stimulation at specific locations that were selected by analyzing the networks activity in real time according to our new information encoding principle. Currently we develop new-generation of neuro chips using special carbon nano tubes (CNT). These electrodes enable to engineer the networks topology and efficient electrical interfacing with the neurons. This advance bears the promise to pave the way for building a new experimental platform for testing new drugs and developing new methods for neural networks repair and regeneration. Looking into the future, the development brings us a step closer towards the dream of Brain Repair by implementable Neuro-Electronic hybrid chips.

Accuracy of Intraoperative Computed Tomography during Deep Brain Stimulation Procedures: Comparison with Postoperative Magnetic Resonance Imaging

PubMed Central

Bot, Maarten; van den Munckhof, Pepijn; Bakay, Roy; Stebbins, Glenn; Verhagen Metman, Leo

2017-01-01

Objective To determine the accuracy of intraoperative computed tomography (iCT) in localizing deep brain stimulation (DBS) electrodes by comparing this modality with postoperative magnetic resonance imaging (MRI). Background Optimal lead placement is a critical factor for the outcome of DBS procedures and preferably confirmed during surgery. iCT offers 3-dimensional verification of both microelectrode and lead location during DBS surgery. However, accurate electrode representation on iCT has not been extensively studied. Methods DBS surgery was performed using the Leksell stereotactic G frame. Stereotactic coordinates of 52 DBS leads were determined on both iCT and postoperative MRI and compared with intended final target coordinates. The resulting absolute differences in X (medial-lateral), Y (anterior-posterior), and Z (dorsal-ventral) coordinates (ΔX, ΔY, and ΔZ) for both modalities were then used to calculate the euclidean distance. Results Euclidean distances were 2.7 ± 1.1 and 2.5 ± 1.2 mm for MRI and iCT, respectively (p = 0.2). Conclusion Postoperative MRI and iCT show equivalent DBS lead representation. Intraoperative localization of both microelectrode and DBS lead in stereotactic space enables direct adjustments. Verification of lead placement with postoperative MRI, considered to be the gold standard, is unnecessary. PMID:28601874

Accuracy of Intraoperative Computed Tomography during Deep Brain Stimulation Procedures: Comparison with Postoperative Magnetic Resonance Imaging.

PubMed

Bot, Maarten; van den Munckhof, Pepijn; Bakay, Roy; Stebbins, Glenn; Verhagen Metman, Leo

2017-01-01

To determine the accuracy of intraoperative computed tomography (iCT) in localizing deep brain stimulation (DBS) electrodes by comparing this modality with postoperative magnetic resonance imaging (MRI). Optimal lead placement is a critical factor for the outcome of DBS procedures and preferably confirmed during surgery. iCT offers 3-dimensional verification of both microelectrode and lead location during DBS surgery. However, accurate electrode representation on iCT has not been extensively studied. DBS surgery was performed using the Leksell stereotactic G frame. Stereotactic coordinates of 52 DBS leads were determined on both iCT and postoperative MRI and compared with intended final target coordinates. The resulting absolute differences in X (medial-lateral), Y (anterior-posterior), and Z (dorsal-ventral) coordinates (ΔX, ΔY, and ΔZ) for both modalities were then used to calculate the euclidean distance. Euclidean distances were 2.7 ± 1.1 and 2.5 ± 1.2 mm for MRI and iCT, respectively (p = 0.2). Postoperative MRI and iCT show equivalent DBS lead representation. Intraoperative localization of both microelectrode and DBS lead in stereotactic space enables direct adjustments. Verification of lead placement with postoperative MRI, considered to be the gold standard, is unnecessary. © 2017 The Author(s) Published by S. Karger AG, Basel.

Bidirectional Modulation of Extinction of Drug Seeking by Deep Brain Stimulation of the Ventral Striatum.

PubMed

Martínez-Rivera, Freddyson J; Rodriguez-Romaguera, Jose; Lloret-Torres, Mario E; Do Monte, Fabricio H; Quirk, Gregory J; Barreto-Estrada, Jennifer L

2016-11-01

Recent research in humans and rodents has explored the use of deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VS) as a possible treatment for drug addiction. However, the optimum electrode placement and optimum DBS parameters have not been thoroughly studied. Here we varied stimulation sites and frequencies to determine whether DBS of the VS could facilitate the extinction of morphine-induced conditioned place preference in rats. Rats were implanted with DBS electrodes in the dorsal or ventral subregions of the VS and trained to the morphine conditioned place preference. Subsequently, rats received extinction sessions over 9 days, combined with 60 min of either high- (130 Hz) or low- (20 Hz) frequency DBS. To study circuit-wide activations after DBS of the VS, c-fos immunohistochemistry was performed in regions involved in the extinction of drug-seeking behaviors. High-frequency DBS of the dorsal-VS impaired both extinction training and extinction memory, whereas high-frequency DBS of the ventral-VS had no effect. In contrast, low-frequency DBS of the dorsal-VS strengthened extinction memory when tested 2 or 9 days after the cessation of stimulation. Both DBS frequencies increased c-fos expression in the infralimbic prefrontal cortex, but only low-frequency DBS increased c-fos expression in the basal amygdala and the medial portion of the central amygdala. Our results suggest that low-frequency (rather than high-frequency) DBS of the dorsal-VS strengthens extinction memory and may be a potential adjunct for extinction-based therapies for treatment-refractory opioid addiction. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Failed DBS for palliation of visual problems in a case of oculopalatal tremor.

PubMed

Wang, David; Sanchez, Justin; Foote, Kelly D; Sudhyadhom, Atchar; Bhatti, M Tariq; Lewis, Steven; Okun, Michael S

2009-01-01

To report the results of attempted bilateral red nucleus (RN) deep brain stimulation (DBS) for the palliative treatment of visual problems associated with oculopalatal tremor (OPT). It is hypothesized that OPT results from a defect in the Guillain-Mollaret triangle, a circuit that includes connections with the dentate nucleus, the contralateral red nucleus, and the inferior olive. We present a high functioning patient (an accountant) who underwent a palliative trial of RN region DBS in an approach targeted through the subthalamic nucleus region. The aim was to reduce eye tremor and improve vision through interruption of the pathologically oscillating circuit in the Guillain-Mollaret triangle. Following informed consent, a patient with OPT (and failure of multiple classes of medication and botulinum toxin therapy) underwent placement of bilateral DBS electrodes within the region of the RN. He underwent preoperative testing and testing after 12 months of continuous stimulation with the device in monopolar, bipolar, low frequency, and high frequency settings. The patient did not demonstrate significant changes in the neurological examination following the procedure and postoperative programming sessions. Eye tremor was monitored pre- and postoperatively by ocular EMG and did not change in frequency. Following the one-year trial, stimulation was discontinued as there were no improvements in vision. DBS for OPT was not clinically effective. There were many potential reasons for failed efficacy including a failure to implant the electrodes deep and medial enough into the target region because of stimulation induced side effects. Other targets within the Guillain-Mollaret circuit (and outside of the circuit) may be more useful, though they may prove to be less safe and even more difficult to access. Better custom designed DBS leads may be needed for such small targets in critical brain regions.

Suppression and facilitation of auditory neurons through coordinated acoustic and midbrain stimulation: investigating a deep brain stimulator for tinnitus

NASA Astrophysics Data System (ADS)

Offutt, Sarah J.; Ryan, Kellie J.; Konop, Alexander E.; Lim, Hubert H.

2014-12-01

Objective. The inferior colliculus (IC) is the primary processing center of auditory information in the midbrain and is one site of tinnitus-related activity. One potential option for suppressing the tinnitus percept is through deep brain stimulation via the auditory midbrain implant (AMI), which is designed for hearing restoration and is already being implanted in deaf patients who also have tinnitus. However, to assess the feasibility of AMI stimulation for tinnitus treatment we first need to characterize the functional connectivity within the IC. Previous studies have suggested modulatory projections from the dorsal cortex of the IC (ICD) to the central nucleus of the IC (ICC), though the functional properties of these projections need to be determined. Approach. In this study, we investigated the effects of electrical stimulation of the ICD on acoustic-driven activity within the ICC in ketamine-anesthetized guinea pigs. Main Results. We observed ICD stimulation induces both suppressive and facilitatory changes across ICC that can occur immediately during stimulation and remain after stimulation. Additionally, ICD stimulation paired with broadband noise stimulation at a specific delay can induce greater suppressive than facilitatory effects, especially when stimulating in more rostral and medial ICD locations. Significance. These findings demonstrate that ICD stimulation can induce specific types of plastic changes in ICC activity, which may be relevant for treating tinnitus. By using the AMI with electrode sites positioned with the ICD and the ICC, the modulatory effects of ICD stimulation can be tested directly in tinnitus patients.

Rational modulation of neuronal processing with applied electric fields.

PubMed

Bikson, Marom; Radman, Thomas; Datta, Abhishek

2006-01-01

Traditional approaches to electrical stimulation, using trains of supra-threshold pulses to trigger action potentials, may be replaced or augmented by using 'rational' sub-threshold stimulation protocols that incorporate knowledge of single neuron geometry, inhomogeneous tissue properties, and nervous system information coding. Sub-threshold stimulation, at intensities (well) below those sufficient to trigger action potentials, may none-the-less exert a profound effect on brain function through modulation of concomitant neuronal activity. For example, small DC fields may coherently polarize a network of neurons and thus modulate the simultaneous processing of afferent synaptic input as well as resulting changes in synaptic plasticity. Through 'activity-dependent plasticity', sub-threshold fields may allow specific targeting of pathological networks and are thus particularly suitable to overcome the poor anatomical focus of noninvasive (transcranial) electrical stimulation. Additional approaches to improve targeting in transcranial stimulation using novel electrode configurations are also introduced.

Electrical stimulation as a means for achieving recovery of function in stroke patients.

PubMed

Popović, Dejan B; Sinkaer, Thomas; Popović, Mirjana B

2009-01-01

This review presents technologies used in and assesses the main clinical outcomes of electrical therapies designed to speed up and increase functional recovery in stroke patients. The review describes methods which interface peripheral systems (e.g., cyclic neural stimulation, stimulation triggered by electrical activity of muscles, therapeutic functional electrical stimulation) and transcranial brain stimulation with surface and implantable electrodes. Our conclusion from reviewing these data is that integration of electrical therapy into exercise-active movement mediated by electrical activation of peripheral and central sensory-motor mechanisms enhances motor re-learning following damage to the central nervous system. Motor re-learning is considered here as a set of processes associated with practice or experience that leads to long-term changes in the capability for movement. An important suggestion is that therapeutic effects are likely to be much more effective when treatment is applied in the acute, rather than in the chronic, phase of stroke.

Individual fiber anatomy of the subthalamic region revealed with diffusion tensor imaging: a concept to identify the deep brain stimulation target for tremor suppression.

PubMed

Coenen, Volker A; Mädler, Burkhard; Schiffbauer, Hagen; Urbach, Horst; Allert, Niels

2011-04-01

Deep brain stimulation (DBS) has been proven to alleviate tremor of various origins. Distinct regions have been targeted. One explanation for good clinical tremor control might be the involvement of the dentatorubrothalamic tract (DRT) as has been suggested in superficial (thalamic) and inferior (posterior subthalamic) target regions. Beyond a correlation with atlas data and the postmortem evaluation of patients treated with lesion surgery, proof for the involvement of DRT in tremor reduction in the living, the scope of this work, is elusive. To report a case of unilateral refractory tremor in tremor-dominant Parkinson disease treated with thalamic DBS. Preoperative diffusion tensor imaging (DTI) was performed. Correlation with individual DBS electrode contact locations was obtained through postoperative fusion of helical computed tomography (CT) data with DTI fiber tracking. Tremor was alleviated effectively. An evaluation of the active electrode contact position revealed clear involvement of the DRT in tremor control. A closer evaluation of clinical effects and side effects revealed a highly detailed individual fiber map of the subthalamic region with DTI fiber tracking. This is the first time the involvement of the DRT in tremor reduction through DBS has been shown in the living. The combination of DTI with postoperative CT and the evaluation of the electrophysiological environment of distinct electrode contacts led to an individual detailed fiber map and might be extrapolated to refined DTI-based targeting strategies in the future. Data acquisition for a larger study group is the topic of our ongoing research.

Deep Brain Stimulation of the Dentato-Rubro-Thalamic Tract: Outcomes of Direct Targeting for Tremor.

PubMed

Fenoy, Albert J; Schiess, Mya C

2017-07-01

Targeting the dentato-rubro-thalamic tract (DRTt) has been suggested to be efficacious in deep brain stimulation (DBS) for tremor suppression, both in case reports and post-hoc analyses. This prospective observational study sought to analyze outcomes after directly targeting the DRTt in tremor patients. 20 consecutively enrolled intention tremor patients obtained pre-operative MRI with diffusion tensor (dTi) sequences. Mean baseline tremor amplitude based on The Essential Tremor Rating Assessment Scale was recorded. The DRTt was drawn for each individual on StealthViz software (Medtronic) using the dentate nucleus as the seed region and the ipsilateral pre-central gyrus as the end region and then directly targeted during surgery. Intraoperative testing confirmed successful tremor control. Post-operative analysis of electrode position relative to the DRTt was performed, as was post-operative assessment of tremor improvement. The mean age of patients was 66.8 years; mean duration of tremor was 16 years. Mean voltage for the L electrode = 3.4 V; R = 2.6 V. Mean distance from the center of the active electrode contact to the DRTt was 0.9 mm on the L, and 0.8 mm on the R. Improvement in arm tremor amplitude from baseline after DBS was significant (P < 0.001). Direct targeting of the DRTt in DBS is an effective strategy for tremor suppression. Accounting for hardware, software, and model limitations, depiction of the DRTt allows for placement of electrode contacts directly within the fiber tract for modulation despite any anatomical variation, which reproducibly resulted in good tremor control. © 2017 International Neuromodulation Society.

The electric field distributions in anatomical head models during transcranial direct current stimulation for post-stroke rehabilitation.

PubMed

Manoli, Zoi; Parazzini, Marta; Ravazzani, Paolo; Samaras, Theodoros

2017-01-01

The lack of knowledge of the electric field distribution inside the brain of stroke patients receiving transcranial direct current stimulation (tDCS) calls for estimating it computationally. Moreover, the impact on this distribution of a novel clinical management approach which involves secondary motor areas (SMA) in stroke rehabilitation needs to be evaluated. Finally, the differences in the electric field distributions due to gender and age need to be investigated. This work presents the development of two different anatomical models (young adult female and elderly male) with an ischemic stroke region of spherical volume 10 cm 3 or 50 cm 3 , using numerical models of the Virtual Population (ViP). The stroke phase was considered as acute or chronic, resulting in different electrical properties of the area. Two different electrode montages were used - One over the lesion area and the contralateral supra-orbital region and the other over the SMA and the contralateral supra-orbital region. A quasi-electrostatic solver was used to numerically solve the Laplace equation with the finite-difference technique. Both the 99th percentile of the electric field intensity distribution ("E peak value") and the percentage of the tissue volumes with electric field intensity over 50% and 70% of the E peak value were assessed inside the target areas of the primary motor cortex (M1) and the SMA, as well as in other brain tissues (hypothalamus and cerebellum). In the acute phase of an ischemic stroke, the normalized electric field intensity distributions do not differ noticeably compared to those in the brain of a healthy person (mean square difference < 2%). The difference becomes larger (up to 4.5%) for the chronic phase of a large ischemic lesion. Moreover, the maximum values of the induced electric field in the tissues in the SMA are almost equal for both electrode montages. The peak values of the electric field distribution ("E peak values") in cerebellum and hypothalamus for both electrode montages are rather small but different from those of healthy patients. The largest difference of 21% decrease with respect to a healthy subject was noticed in the elder adult model with a large chronic lesion. The comparison of the different electrode montages shows that the use of a stimulating electrode over the affected area creates larger values of the electric field in M1, by up to 26% for a small chronic lesion in the young female model. On the contrary, the montage does not affect considerably (change less than 8%) the E peak values in the SMA. This implies that for exciting M1, the M1-Fp2 montage should be favored. The presence and the phase of an ischemic stroke lesion, as well as the configuration of electrode montages affect the distribution and the maximum value of the electric field induced in tissues. Moreover, patients whom seem to benefit most from tDCS are those in the chronic phase of an ischemic stroke, since contrasts in the tissue conductivity result in a higher electric field induced around the lesion volume, which could stimulate the remaining healthy tissue in the area. © 2016 American Association of Physicists in Medicine.

Development of nanowire arrays for neural probe

NASA Astrophysics Data System (ADS)

Abraham, Jose K.; Xie, Jining; Varadan, Vijay K.

2005-05-01

It is already established that functional electrical stimulation is an effective way to restore many functions of the brain in disabled individuals. The electrical stimulation can be done by using an array of electrodes. Neural probes stimulate or sense the biopotentials mainly through the exposed metal sites. These sites should be smaller relative to the spatial potential distribution so that any potential averaging in the sensing area can be avoided. At the same time, the decrease in size of these sensing sites is limited due to the increase in impedance levels and the thermal noise while decreasing its size. It is known that current density in a planar electrode is not uniform and a higher current density can be observer around the perimeter of the electrodes. Electrical measurements conducted on many nanotubes and nanowires have already proved that it could be possible to use for current density applications and the drawbacks of the present design in neural probes can be overcome by incorporating many nanotechnology solutions. In this paper we present the design and development of nanowire arrays for the neural probe for the multisite contact which has the ability to collect and analyze isolated single unit activity. An array of vertically grown nanowires is used as contact site and many of such arrays can be used for stimulating as well as recording sites. The nanolevel interaction and wireless communication solution can extend to applications involving the treatment of many neurological disorders including Parkinson"s disease, Alzheimer"s disease, spinal injuries and the treatment of blindness and paralyzed patients with minimal or no invasive surgical procedures.

Bio-inspired hybrid microelectrodes: a hybrid solution to improve long-term performance of chronic intracortical implants.

PubMed

De Faveri, Sara; Maggiolini, Emma; Miele, Ermanno; De Angelis, Francesco; Cesca, Fabrizia; Benfenati, Fabio; Fadiga, Luciano

2014-01-01

The use of implants that allow chronic electrical stimulation and recording in the brain of human patients is currently limited by a series of events that cause the deterioration over time of both the electrode surface and the surrounding tissue. The main reason of failure is the tissue inflammatory reaction that eventually causes neuronal loss and glial encapsulation, resulting in a progressive increase of the electrode-electrolyte impedance. Here, we describe a new method to create bio-inspired electrodes to mimic the mechanical properties and biological composition of the host tissue. This combination has a great potential to increase the implant lifetime by reducing tissue reaction and improving electrical coupling. Our method implies coating the electrode with reprogrammed neural or glial cells encapsulated within a hydrogel layer. We chose fibrin as a hydrogel and primary hippocampal neurons or astrocytes from rat brain as cellular layer. We demonstrate that fibrin coating is highly biocompatible, forms uniform coatings of controllable thickness, does not alter the electrochemical properties of the microelectrode and allows good quality recordings. Moreover, it reduces the amount of host reactive astrocytes - over time - compared to a bare wire and is fully reabsorbed by the surrounding tissue within 7 days after implantation, avoiding the common problem of hydrogels swelling. Both astrocytes and neurons could be successfully grown onto the electrode surface within the fibrin hydrogel without altering the electrochemical properties of the microelectrode. This bio-hybrid device has therefore a good potential to improve the electrical integration at the neuron-electrode interface and support the long-term success of neural prostheses.

Mathematical modeling of chemotaxis and glial scarring around implanted electrodes

NASA Astrophysics Data System (ADS)

Silchenko, Alexander N.; Tass, Peter A.

2015-02-01

It is well known that the implantation of electrodes for deep brain stimulation or microelectrode probes for the recording of neuronal activity is always accompanied by the response of the brain’s immune system leading to the formation of a glial scar around the implantation sites. The implantation of electrodes causes massive release of adenosine-5‧-triphosphate (ATP) and different cytokines into the extracellular space and activates the microglia. The released ATP and the products of its hydrolysis, such as ADP and adenosine, become the main elements mediating chemotactic sensitivity and motility of microglial cells via subsequent activation of P2Y2,12 as well as A3A/A2A adenosine receptors. The size and density of an insulating sheath around the electrode, formed by microglial cells, are important criteria for the optimization of the signal-to-noise ratio during microelectrode recordings or parameters of electrical current delivered to the brain tissue. Here, we study a purinergic signaling pathway underlying the chemotactic motion of microglia towards implanted electrodes as well as the possible impact of an anti-inflammatory coating consisting of the interleukin-1 receptor antagonist. We present a model describing the formation of a stable aggregate around the electrode due to the joint chemo-attractive action of ATP and ADP and the mixed influence of extracellular adenosine. The bioactive coating is modeled as a source of chemo-repellent located near the electrode surface. The obtained analytical and numerical results allowed us to reveal the dependences of size and spatial location of the insulating sheath on the amount of released ATP and estimate the impact of immune suppressive coating on the scarring process.

Selective Neuronal Activation by Cochlear Implant Stimulation in Auditory Cortex of Awake Primate

PubMed Central

Johnson, Luke A.; Della Santina, Charles C.

2016-01-01

Despite the success of cochlear implants (CIs) in human populations, most users perform poorly in noisy environments and music and tonal language perception. How CI devices engage the brain at the single neuron level has remained largely unknown, in particular in the primate brain. By comparing neuronal responses with acoustic and CI stimulation in marmoset monkeys unilaterally implanted with a CI electrode array, we discovered that CI stimulation was surprisingly ineffective at activating many neurons in auditory cortex, particularly in the hemisphere ipsilateral to the CI. Further analyses revealed that the CI-nonresponsive neurons were narrowly tuned to frequency and sound level when probed with acoustic stimuli; such neurons likely play a role in perceptual behaviors requiring fine frequency and level discrimination, tasks that CI users find especially challenging. These findings suggest potential deficits in central auditory processing of CI stimulation and provide important insights into factors responsible for poor CI user performance in a wide range of perceptual tasks. SIGNIFICANCE STATEMENT The cochlear implant (CI) is the most successful neural prosthetic device to date and has restored hearing in hundreds of thousands of deaf individuals worldwide. However, despite its huge successes, CI users still face many perceptual limitations, and the brain mechanisms involved in hearing through CI devices remain poorly understood. By directly comparing single-neuron responses to acoustic and CI stimulation in auditory cortex of awake marmoset monkeys, we discovered that neurons unresponsive to CI stimulation were sharply tuned to frequency and sound level. Our results point out a major deficit in central auditory processing of CI stimulation and provide important insights into mechanisms underlying the poor CI user performance in a wide range of perceptual tasks. PMID:27927962

The Effect of a Transcranial Channel as a Skull/Brain Interface in High-Definition Transcranial Direct Current Stimulation—A Computational Study

NASA Astrophysics Data System (ADS)

Seo, Hyeon; Kim, Hyoung-Ihl; Jun, Sung Chan

2017-01-01

A transcranial channel is an interface between the skull and brain; it consists of a biocompatible and highly conductive material that helps convey the current induced by transcranial direct current stimulation (tDCS) to the target area. However, it has been proposed only conceptually, and there has been no concrete study of its efficacy. In this work, we conducted a computational investigation of this conceptual transcranial model with high-definition tDCS, inducing focalized neuromodulation to determine whether inclusion of a transcranial channel performs effectively. To do so, we constructed an anatomically realistic head model and compartmental pyramidal neuronal models. We analyzed membrane polarization by extracellular stimulation and found that the inclusion of a transcranial channel induced polarization at the target area 11 times greater than conventional HD-tDCS without the transcranial channel. Furthermore, the stimulation effect of the transcranial channel persisted up to approximately 80%, even when the stimulus electrodes were displaced approximately 5 mm from the target area. We investigated the efficacy of the transcranial channel and found that greatly improved stimulation intensity and focality may be achieved. Thus, the use of these channels may be promising for clinical treatment.

Evaluation of focused multipolar stimulation for cochlear implants: a preclinical safety study

NASA Astrophysics Data System (ADS)

Shepherd, Robert K.; Wise, Andrew K.; Enke, Ya Lang; Carter, Paul M.; Fallon, James B.

2017-08-01

Objective. Cochlear implants (CIs) have a limited number of independent stimulation channels due to the highly conductive nature of the fluid-filled cochlea. Attempts to develop highly focused stimulation to improve speech perception in CI users includes the use of simultaneous stimulation via multiple current sources. Focused multipolar (FMP) stimulation is an example of this approach and has been shown to reduce interaction between stimulating channels. However, compared with conventional biphasic current pulses generated from a single current source, FMP is a complex stimulus that includes extended periods of stimulation before charge recovery is achieved, raising questions on whether chronic stimulation with this strategy is safe. The present study evaluated the long-term safety of intracochlear stimulation using FMP in a preclinical animal model of profound deafness. Approach. Six cats were bilaterally implanted with scala tympani electrode arrays two months after deafening, and received continuous unilateral FMP stimulation at levels that evoked a behavioural response for periods of up to 182 d. Electrode impedance, electrically-evoked compound action potentials (ECAPs) and auditory brainstem responses (EABRs) were monitored periodically over the course of the stimulation program from both the stimulated and contralateral control cochleae. On completion of the stimulation program cochleae were examined histologically and the electrode arrays were evaluated for evidence of platinum (Pt) corrosion. Main results. There was no significant difference in electrode impedance between control and chronically stimulated electrodes following long-term FMP stimulation. Moreover, there was no significant difference between ECAP and EABR thresholds evoked from control or stimulated cochleae at either the onset of stimulation or at completion of the stimulation program. Chronic FMP stimulation had no effect on spiral ganglion neuron (SGN) survival when compared with unstimulated control cochleae. Long-term implantation typically evoked a mild foreign body reaction proximal to the electrode array; however stimulated cochleae exhibited a small but statistically significant increase in the tissue response. Finally, there was no evidence of Pt corrosion following long-term FMP stimulation; stimulated electrodes exhibited the same surface features as the unstimulated control electrodes. Significance. Chronic intracochlear FMP stimulation at levels used in the present study did not adversely affect electrically-evoked neural thresholds or SGN survival but evoked a small, benign increase in inflammatory response compared to control ears. Moreover chronic FMP stimulation does not affect the surface of Pt electrodes at suprathreshold stimulus levels. These findings support the safe clinical application of an FMP stimulation strategy.

Pudendal nerve stimulation and block by a wireless-controlled implantable stimulator in cats.

PubMed

Yang, Guangning; Wang, Jicheng; Shen, Bing; Roppolo, James R; de Groat, William C; Tai, Changfeng

2014-07-01

The study aims to determine the functionality of a wireless-controlled implantable stimulator designed for stimulation and block of the pudendal nerve. In five cats under α-chloralose anesthesia, the stimulator was implanted underneath the skin on the left side in the lower back along the sacral spine. Two tripolar cuff electrodes were implanted bilaterally on the pudendal nerves in addition to one bipolar cuff electrode that was implanted on the left side central to the tripolar cuff electrode. The stimulator provided high-frequency (5-20 kHz) biphasic stimulation waveforms to the two tripolar electrodes and low-frequency (1-100 Hz) rectangular pulses to the bipolar electrode. Bladder and urethral pressures were measured to determine the effects of pudendal nerve stimulation (PNS) or block. The maximal (70-100 cmH2O) urethral pressure generated by 20-Hz PNS applied via the bipolar electrode was completely eliminated by the pudendal nerve block induced by the high-frequency stimulation (6-15 kHz, 6-10 V) applied via the two tripolar electrodes. In a partially filled bladder, 20-30 Hz PNS (2-8 V, 0.2 ms) but not 5 Hz stimulation applied via the bipolar electrode elicited a large sustained bladder contraction (45.9 ± 13.4 to 52.0 ± 22 cmH2O). During cystometry, the 5 Hz PNS significantly (p < 0.05) increased bladder capacity to 176.5 ± 27.1% of control capacity. The wireless-controlled implantable stimulator successfully generated the required waveforms for stimulation and block of pudendal nerve, which will be useful for restoring bladder functions after spinal cord injury. © 2013 International Neuromodulation Society.

The effects of chronic intracortical microstimulation on neural tissue and fine motor behavior.

PubMed

Rajan, Alexander T; Boback, Jessica L; Dammann, John F; Tenore, Francesco V; Wester, Brock A; Otto, Kevin J; Gaunt, Robert A; Bensmaia, Sliman J

2015-12-01

One approach to conveying sensory feedback in neuroprostheses is to electrically stimulate sensory neurons in the cortex. For this approach to be viable, it is critical that intracortical microstimulation (ICMS) causes minimal damage to the brain. Here, we investigate the effects of chronic ICMS on the neuronal tissue across a variety of stimulation regimes in non-human primates. We also examine each animal's ability to use their hand--the cortical representation of which is targeted by the ICMS--as a further assay of possible neuronal damage. We implanted electrode arrays in the primary somatosensory cortex of three Rhesus macaques and delivered ICMS four hours per day, five days per week, for six months. Multiple regimes of ICMS were delivered to investigate the effects of stimulation parameters on the tissue and behavior. Parameters included current amplitude (10-100 μA), pulse train duration (1, 5 s), and duty cycle (1/1, 1/3). We then performed a range of histopathological assays on tissue near the tips of both stimulated and unstimulated electrodes to assess the effects of chronic ICMS on the tissue and their dependence on stimulation parameters. While the implantation and residence of the arrays in the cortical tissue did cause significant damage, chronic ICMS had no detectable additional effect; furthermore, the animals exhibited no impairments in fine motor control. Chronic ICMS may be a viable means to convey sensory feedback in neuroprostheses as it does not cause significant damage to the stimulated tissue.

The effects of chronic intracortical microstimulation on neural tissue and fine motor behavior

NASA Astrophysics Data System (ADS)

Rajan, Alexander T.; Boback, Jessica L.; Dammann, John F.; Tenore, Francesco V.; Wester, Brock A.; Otto, Kevin J.; Gaunt, Robert A.; Bensmaia, Sliman J.

2015-12-01

Objective. One approach to conveying sensory feedback in neuroprostheses is to electrically stimulate sensory neurons in the cortex. For this approach to be viable, it is critical that intracortical microstimulation (ICMS) causes minimal damage to the brain. Here, we investigate the effects of chronic ICMS on the neuronal tissue across a variety of stimulation regimes in non-human primates. We also examine each animal’s ability to use their hand—the cortical representation of which is targeted by the ICMS—as a further assay of possible neuronal damage. Approach. We implanted electrode arrays in the primary somatosensory cortex of three Rhesus macaques and delivered ICMS four hours per day, five days per week, for six months. Multiple regimes of ICMS were delivered to investigate the effects of stimulation parameters on the tissue and behavior. Parameters included current amplitude (10-100 μA), pulse train duration (1, 5 s), and duty cycle (1/1, 1/3). We then performed a range of histopathological assays on tissue near the tips of both stimulated and unstimulated electrodes to assess the effects of chronic ICMS on the tissue and their dependence on stimulation parameters. Main results. While the implantation and residence of the arrays in the cortical tissue did cause significant damage, chronic ICMS had no detectable additional effect; furthermore, the animals exhibited no impairments in fine motor control. Significance. Chronic ICMS may be a viable means to convey sensory feedback in neuroprostheses as it does not cause significant damage to the stimulated tissue.

Complications and results of subdural grid electrode implantation in epilepsy surgery.

PubMed

Lee, W S; Lee, J K; Lee, S A; Kang, J K; Ko, T S

2000-11-01

We assessed the risk of delayed subdural hematoma and other complications associated with subdural grid implantation. Forty-nine patients underwent subdural grid implantation with/without subdural strips or depth electrodes from January 1994 to August 1998. To identify the risk associated with subdural grid implantation, a retrospective review of all patients' medical records and radiological studies was performed. The major complications of 50 subdural grid electrode implantations were as follows: four cases (7.8%) of delayed subdural hematoma at the site of the subdural grid, requiring emergency operation; two cases (3.9%) of infection; one case (2.0%) of epidural hematoma; and one case (2.0%) of brain swelling. After subdural hematoma removal, the electrodes were left in place. CCTV monitoring and cortical stimulation studies were continued thereafter. No delayed subdural hematoma has occurred since routine placement of subdural drains was begun. In our experience the worst complication of subdural grid implantation has been delayed subdural hematoma. Placement of subdural drains and close observation may be helpful to prevent this serious complication.

Reanimating the arm and hand with intraspinal microstimulation

NASA Astrophysics Data System (ADS)

Zimmermann, Jonas B.; Seki, Kazuhiko; Jackson, Andrew

2011-10-01

To date, there is no effective therapy for spinal cord injury, and many patients could benefit dramatically from at least partial restoration of arm and hand function. Despite a substantial body of research investigating intraspinal microstimulation (ISMS) in frogs, rodents and cats, little is known about upper-limb responses to cervical stimulation in the primate. Here, we show for the first time that long trains of ISMS delivered to the macaque spinal cord can evoke functional arm and hand movements. Complex movements involving coordinated activation of multiple muscles could be elicited from a single electrode, while just two electrodes were required for independent control of reaching and grasping. We found that the motor responses to ISMS were described by a dual exponential model that depended only on stimulation history. We demonstrate that this model can be inverted to generate stimulus trains capable of eliciting arbitrary, graded motor responses, and could be used to restore volitional movements in a closed-loop brain-machine interface.

[Pallidal and subthalamic stimulation in Parkinson's disease: lessons from the unsatisfactory results].

PubMed

2001-01-01

Deep brain stimulation is being widely used in advanced Parkinson's disease (PD). Outcome determinants are not known. Some relevant data about outcome may be obtained from the study of patients with unsatisfactory results. We have retrospectively analyzed the number and causes of unsatisfactory results (insufficient improvement 6 months after the intervention) in 211 patients. Forty patients (18.9%) experienced an unsatisfactory result. Inadequate clinical selection by advanced age, abnormal MRI and levodopa unresponsive symptoms was the main cause in 28 cases. In 11 patients a misplacement of the electrode was reported. In 2 cases no cause was identified. Thirty-four out of the 40 patients corresponded to the early experience of the teams involved in the study. We conclude that the main factors responsible for a negative outcome are related to the inadequate clinical selection of the patients and the incorrect placement of the electrode. The experience of the team may also be a key factor.

A Nerve Clamp Electrode Design for Indirect Stimulation of Skeletal Muscle

DTIC Science & Technology

2010-10-01

neurons. This device enables stimulation of muscle contraction indirectly as opposed to contraction from direct muscle stimulation. The electrode is able...to stimulate indirect muscle contraction when tested on ex vivo preparations from rodent phrenic nerve-hemidiaphragm muscle in similar fashion to...unsuccessful in stimulating indirect muscle contraction . Therefore, this novel electrode is useful for physiological assessment of nerve agents and

Neural feedback for instantaneous spatiotemporal modulation of afferent pathways in bi-directional brain-machine interfaces.

PubMed

Liu, Jianbo; Khalil, Hassan K; Oweiss, Karim G

2011-10-01

In bi-directional brain-machine interfaces (BMIs), precisely controlling the delivery of microstimulation, both in space and in time, is critical to continuously modulate the neural activity patterns that carry information about the state of the brain-actuated device to sensory areas in the brain. In this paper, we investigate the use of neural feedback to control the spatiotemporal firing patterns of neural ensembles in a model of the thalamocortical pathway. Control of pyramidal (PY) cells in the primary somatosensory cortex (S1) is achieved based on microstimulation of thalamic relay cells through multiple-input multiple-output (MIMO) feedback controllers. This closed loop feedback control mechanism is achieved by simultaneously varying the stimulation parameters across multiple stimulation electrodes in the thalamic circuit based on continuous monitoring of the difference between reference patterns and the evoked responses of the cortical PY cells. We demonstrate that it is feasible to achieve a desired level of performance by controlling the firing activity pattern of a few "key" neural elements in the network. Our results suggest that neural feedback could be an effective method to facilitate the delivery of information to the cortex to substitute lost sensory inputs in cortically controlled BMIs.

The functional neuroanatomy of pleasure and happiness.

PubMed

Kringelbach, Morten L; Berridge, Kent C

2010-06-01

Over fifty years ago the discovery that rats would work to electrically stimulate their brains suggested the intriguing possibility that bliss could be achieved through the use of 'pleasure electrodes' implanted deep within the brain. Subsequent research has failed to bring about this brave new world of boundless pleasure, but more recent findings have started to throw new light on the intriguing links between brain mechanisms of pleasure and happiness. We discuss these findings of the underlying neural mechanisms and functional neuroanatomy of pleasure in the brain. In particular we address how they may come to shed light on our understanding of the brain basis of happiness. Beyond sensory pleasures, we examine how higher pleasures may be related to the brain's default networks, especially in orchestrating cognitive aspects of the meaningfulness important to happiness. We also address how understanding of the hedonic brain might help alleviate the suffering caused by the lack of pleasure, anhedonia, which is a central feature of affective disorders such as depression and chronic pain.

On the road to a neuroprosthetic hand: a novel hand grasp orthosis based on functional electrical stimulation.

PubMed

Leeb, Robert; Gubler, Miguel; Tavella, Michele; Miller, Heather; Del Millan, Jose R

2010-01-01

To patients who have lost the functionality of their hands as a result of a severe spinal cord injury or brain stroke, the development of new techniques for grasping is indispensable for reintegration and independency in daily life. Functional Electrical Stimulation (FES) of residual muscles can reproduce the most dominant grasping tasks and can be initialized by brain signals. However, due to the very complex hand anatomy and current limitations in FES-technology with surface electrodes, these grasp patterns cannot be smoothly executed. In this paper, we present an adaptable passive hand orthosis which is capable of producing natural and smooth movements when coupled with FES. It evenly synchronizes the grasping movements and applied forces on all fingers, allowing for naturalistic gestures and functional grasps of everyday objects. The orthosis is also equipped with a lock, which allows it to remain in the desired position without the need for long-term stimulation. Furthermore, we quantify improvements offered by the orthosis compare them with natural grasps on healthy subjects.

Dr. Robert G. Heath: a controversial figure in the history of deep brain stimulation.

PubMed

O'Neal, Christen M; Baker, Cordell M; Glenn, Chad A; Conner, Andrew K; Sughrue, Michael E

2017-09-01

The history of psychosurgery is filled with tales of researchers pushing the boundaries of science and ethics. These stories often create a dark historical framework for some of the most important medical and surgical advancements. Dr. Robert G. Heath, a board-certified neurologist, psychiatrist, and psychoanalyst, holds a debated position within this framework and is most notably remembered for his research on schizophrenia. Dr. Heath was one of the first physicians to implant electrodes in deep cortical structures as a psychosurgical intervention. He used electrical stimulation in an attempt to cure patients with schizophrenia and as a method of conversion therapy in a homosexual man. This research was highly controversial, even prior to the implementation of current ethics standards for clinical research and often goes unmentioned within the historical narrative of deep brain stimulation (DBS). While distinction between the modern practice of DBS and its controversial origins is necessary, it is important to examine Dr. Heath's work as it allows for reflection on current neurosurgical practices and questioning the ethical implication of these advancements.

Focused intracochlear electric stimulation with phased array channels.

PubMed

van den Honert, Chris; Kelsall, David C

2007-06-01

A method is described for producing focused intracochlear electric stimulation using an array of N electrodes. For each electrode site, N weights are computed that define the ratios of positive and negative electrode currents required to produce cancellation of the voltage within scala tympani at all of the N-1 other sites. Multiple sites can be stimulated simultaneously by superposition of their respective current vectors. The method allows N independent stimulus waveforms to be delivered to each of the N electrode sites without spatial overlap. Channel interaction from current spread associated with monopolar stimulation is substantially eliminated. The method operates by inverting the spread functions of individual monopoles as measured with the other electrodes. The method was implemented and validated with data from three human subjects implanted with 22-electrode perimodiolar arrays. Results indicate that (1) focusing is realizable with realistic precision; (2) focusing comes at the cost of increased total stimulation current; (3) uncanceled voltages that arise beyond the ends of the array are weak except when stimulating the two end channels; and (4) close perimodiolar positioning of the electrodes may be important for minimizing stimulation current and sensitivity to measurement errors.

Atlas-Independent, Electrophysiological Mapping of the Optimal Locus of Subthalamic Deep Brain Stimulation for the Motor Symptoms of Parkinson Disease.

PubMed

Conrad, Erin C; Mossner, James M; Chou, Kelvin L; Patil, Parag G

2018-05-23

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms of Parkinson disease (PD). However, motor outcomes can be variable, perhaps due to inconsistent positioning of the active contact relative to an unknown optimal locus of stimulation. Here, we determine the optimal locus of STN stimulation in a geometrically unconstrained, mathematically precise, and atlas-independent manner, using Unified Parkinson Disease Rating Scale (UPDRS) motor outcomes and an electrophysiological neuronal stimulation model. In 20 patients with PD, we mapped motor improvement to active electrode location, relative to the individual, directly MRI-visualized STN. Our analysis included a novel, unconstrained and computational electrical-field model of neuronal activation to estimate the optimal locus of DBS. We mapped the optimal locus to a tightly defined ovoid region 0.49 mm lateral, 0.88 mm posterior, and 2.63 mm dorsal to the anatomical midpoint of the STN. On average, this locus is 11.75 lateral, 1.84 mm posterior, and 1.08 mm ventral to the mid-commissural point. Our novel, atlas-independent method reveals a single, ovoid optimal locus of stimulation in STN DBS for PD. The methodology, here applied to UPDRS and PD, is generalizable to atlas-independent mapping of other motor and non-motor effects of DBS. © 2018 S. Karger AG, Basel.

Je pense donc je fais: transcranial direct current stimulation modulates brain oscillations associated with motor imagery and movement observation.

PubMed

Lapenta, Olivia M; Minati, Ludovico; Fregni, Felipe; Boggio, Paulo S

2013-01-01

Motor system neural networks are activated during movement imagery, observation and execution, with a neural signature characterized by suppression of the Mu rhythm. In order to investigate the origin of this neurophysiological marker, we tested whether transcranial direct current stimulation (tDCS) modifies Mu rhythm oscillations during tasks involving observation and imagery of biological and non-biological movements. We applied tDCS (anodal, cathodal, and sham) in 21 male participants (mean age 23.8 ± 3.06), over the left M1 with a current of 2 mA for 20 min. Following this, we recorded the EEG at C3, C4, and Cz and surrounding C3 and C4 electrodes. Analyses of C3 and C4 showed significant effects for biological vs. non-biological movement (p = 0.005), and differential hemisphere effects according to the type of stimulation (p = 0.04) and type of movement (p = 0.02). Analyses of surrounding electrodes revealed significant interaction effects considering type of stimulation and imagery or observation of biological or non-biological movement (p = 0.03). The main findings of this study were (1) Mu desynchronization during biological movement of the hand region in the contralateral hemisphere after sham tDCS; (2) polarity-dependent modulation effects of tDCS on the Mu rhythm, i.e., anodal tDCS led to Mu synchronization while cathodal tDCS led to Mu desynchronization during movement observation and imagery (3) specific focal and opposite inter-hemispheric effects, i.e., contrary effects for the surrounding electrodes during imagery condition and also for inter-hemispheric electrodes (C3 vs. C4). These findings provide insights into the cortical oscillations during movement observation and imagery. Furthermore, it shows that tDCS can be highly focal when guided by a behavioral task.

The subthalamic microlesion story in Parkinson's disease: electrode insertion-related motor improvement with relative cortico-subcortical hypoactivation in fMRI.

PubMed

Jech, Robert; Mueller, Karsten; Urgošík, Dušan; Sieger, Tomáš; Holiga, Štefan; Růžička, Filip; Dušek, Petr; Havránková, Petra; Vymazal, Josef; Růžička, Evžen

2012-01-01

Electrode implantation into the subthalamic nucleus for deep brain stimulation in Parkinson's disease (PD) is associated with a temporary motor improvement occurring prior to neurostimulation. We studied this phenomenon by functional magnetic resonance imaging (fMRI) when considering the Unified Parkinson's Disease Rating Scale (UPDRS-III) and collateral oedema. Twelve patients with PD (age 55.9± (SD)6.8 years, PD duration 9-15 years) underwent bilateral electrode implantation into the subthalamic nucleus. The fMRI was carried out after an overnight withdrawal of levodopa (OFF condition): (i) before and (ii) within three days after surgery in absence of neurostimulation. The motor task involved visually triggered finger tapping. The OFF/UPDRS-III score dropped from 33.8±8.7 before to 23.3±4.8 after the surgery (p<0.001), correlating with the postoperative oedema score (p<0.05). During the motor task, bilateral activation of the thalamus and basal ganglia, motor cortex and insula were preoperatively higher than after surgery (p<0.001). The results became more enhanced after compensation for the oedema and UPDRS-III scores. In addition, the rigidity and axial symptoms score correlated inversely with activation of the putamen and globus pallidus (p<0.0001). One month later, the OFF/UPDRS-III score had returned to the preoperative level (35.8±7.0, p = 0.4).In conclusion, motor improvement induced by insertion of an inactive electrode into the subthalamic nucleus caused an acute microlesion which was at least partially related to the collateral oedema and associated with extensive impact on the motor network. This was postoperatively manifested as lowered movement-related activation at the cortical and subcortical levels and differed from the known effects of neurostimulation or levodopa. The motor system finally adapted to the microlesion within one month as suggested by loss of motor improvement and good efficacy of deep brain stimulation.

The Subthalamic Microlesion Story in Parkinson's Disease: Electrode Insertion-Related Motor Improvement with Relative Cortico-Subcortical Hypoactivation in fMRI

PubMed Central

Urgošík, Dušan; Sieger, Tomáš; Holiga, Štefan; Růžička, Filip; Dušek, Petr; Havránková, Petra; Vymazal, Josef; Růžička, Evžen

2012-01-01

Electrode implantation into the subthalamic nucleus for deep brain stimulation in Parkinson's disease (PD) is associated with a temporary motor improvement occurring prior to neurostimulation. We studied this phenomenon by functional magnetic resonance imaging (fMRI) when considering the Unified Parkinson's Disease Rating Scale (UPDRS-III) and collateral oedema. Twelve patients with PD (age 55.9± (SD)6.8 years, PD duration 9–15 years) underwent bilateral electrode implantation into the subthalamic nucleus. The fMRI was carried out after an overnight withdrawal of levodopa (OFF condition): (i) before and (ii) within three days after surgery in absence of neurostimulation. The motor task involved visually triggered finger tapping. The OFF/UPDRS-III score dropped from 33.8±8.7 before to 23.3±4.8 after the surgery (p<0.001), correlating with the postoperative oedema score (p<0.05). During the motor task, bilateral activation of the thalamus and basal ganglia, motor cortex and insula were preoperatively higher than after surgery (p<0.001). The results became more enhanced after compensation for the oedema and UPDRS-III scores. In addition, the rigidity and axial symptoms score correlated inversely with activation of the putamen and globus pallidus (p<0.0001). One month later, the OFF/UPDRS-III score had returned to the preoperative level (35.8±7.0, p = 0.4). In conclusion, motor improvement induced by insertion of an inactive electrode into the subthalamic nucleus caused an acute microlesion which was at least partially related to the collateral oedema and associated with extensive impact on the motor network. This was postoperatively manifested as lowered movement-related activation at the cortical and subcortical levels and differed from the known effects of neurostimulation or levodopa. The motor system finally adapted to the microlesion within one month as suggested by loss of motor improvement and good efficacy of deep brain stimulation. PMID:23145068

Optimized programming algorithm for cylindrical and directional deep brain stimulation electrodes.

PubMed

Anderson, Daria Nesterovich; Osting, Braxton; Vorwerk, Johannes; Dorval, Alan D; Butson, Christopher R

2018-04-01

Deep brain stimulation (DBS) is a growing treatment option for movement and psychiatric disorders. As DBS technology moves toward directional leads with increased numbers of smaller electrode contacts, trial-and-error methods of manual DBS programming are becoming too time-consuming for clinical feasibility. We propose an algorithm to automate DBS programming in near real-time for a wide range of DBS lead designs. Magnetic resonance imaging and diffusion tensor imaging are used to build finite element models that include anisotropic conductivity. The algorithm maximizes activation of target tissue and utilizes the Hessian matrix of the electric potential to approximate activation of neurons in all directions. We demonstrate our algorithm's ability in an example programming case that targets the subthalamic nucleus (STN) for the treatment of Parkinson's disease for three lead designs: the Medtronic 3389 (four cylindrical contacts), the direct STNAcute (two cylindrical contacts, six directional contacts), and the Medtronic-Sapiens lead (40 directional contacts). The optimization algorithm returns patient-specific contact configurations in near real-time-less than 10 s for even the most complex leads. When the lead was placed centrally in the target STN, the directional leads were able to activate over 50% of the region, whereas the Medtronic 3389 could activate only 40%. When the lead was placed 2 mm lateral to the target, the directional leads performed as well as they did in the central position, but the Medtronic 3389 activated only 2.9% of the STN. This DBS programming algorithm can be applied to cylindrical electrodes as well as novel directional leads that are too complex with modern technology to be manually programmed. This algorithm may reduce clinical programming time and encourage the use of directional leads, since they activate a larger volume of the target area than cylindrical electrodes in central and off-target lead placements.

Selective electrical interfaces with the nervous system.

PubMed

Rutten, Wim L C

2002-01-01

To achieve selective electrical interfacing to the neural system it is necessary to approach neuronal elements on a scale of micrometers. This necessitates microtechnology fabrication and introduces the interdisciplinary field of neurotechnology, lying at the juncture of neuroscience with microtechnology. The neuroelectronic interface occurs where the membrane of a cell soma or axon meets a metal microelectrode surface. The seal between these may be narrow or may be leaky. In the latter case the surrounding volume conductor becomes part of the interface. Electrode design for successful interfacing, either for stimulation or recording, requires good understanding of membrane phenomena, natural and evoked action potential generation, volume conduction, and electrode behavior. Penetrating multimicroelectrodes have been produced as one-, two-, and three-dimensional arrays, mainly in silicon, glass, and metal microtechnology. Cuff electrodes circumvent a nerve; their selectivity aims at fascicles more than at nerve fibers. Other types of electrodes are regenerating sieves and cone-ingrowth electrodes. The latter may play a role in brain-computer interfaces. Planar substrate-embedded electrode arrays with cultured neural cells on top are used to study the activity and plasticity of developing neural networks. They also serve as substrates for future so-called cultured probes.

Effects of Electrical Stimulation in the Inferior Colliculus on Frequency Discrimination by Rhesus Monkeys and Implications for the Auditory Midbrain Implant

PubMed Central

Ross, Deborah A.; Puñal, Vanessa M.; Agashe, Shruti; Dweck, Isaac; Mueller, Jerel; Grill, Warren M.; Wilson, Blake S.

2016-01-01

Understanding the relationship between the auditory selectivity of neurons and their contribution to perception is critical to the design of effective auditory brain prosthetics. These prosthetics seek to mimic natural activity patterns to achieve desired perceptual outcomes. We measured the contribution of inferior colliculus (IC) sites to perception using combined recording and electrical stimulation. Monkeys performed a frequency-based discrimination task, reporting whether a probe sound was higher or lower in frequency than a reference sound. Stimulation pulses were paired with the probe sound on 50% of trials (0.5–80 μA, 100–300 Hz, n = 172 IC locations in 3 rhesus monkeys). Electrical stimulation tended to bias the animals' judgments in a fashion that was coarsely but significantly correlated with the best frequency of the stimulation site compared with the reference frequency used in the task. Although there was considerable variability in the effects of stimulation (including impairments in performance and shifts in performance away from the direction predicted based on the site's response properties), the results indicate that stimulation of the IC can evoke percepts correlated with the frequency-tuning properties of the IC. Consistent with the implications of recent human studies, the main avenue for improvement for the auditory midbrain implant suggested by our findings is to increase the number and spatial extent of electrodes, to increase the size of the region that can be electrically activated, and to provide a greater range of evoked percepts. SIGNIFICANCE STATEMENT Patients with hearing loss stemming from causes that interrupt the auditory pathway after the cochlea need a brain prosthetic to restore hearing. Recently, prosthetic stimulation in the human inferior colliculus (IC) was evaluated in a clinical trial. Thus far, speech understanding was limited for the subjects and this limitation is thought to be partly due to challenges in harnessing the sound frequency representation in the IC. Here, we tested the effects of IC stimulation in monkeys trained to report the sound frequencies they heard. Our results indicate that the IC can be used to introduce a range of frequency percepts and suggest that placement of a greater number of electrode contacts may improve the effectiveness of such implants. PMID:27147659

A Simple and Accurate Model to Predict Responses to Multi-electrode Stimulation in the Retina

PubMed Central

Maturana, Matias I.; Apollo, Nicholas V.; Hadjinicolaou, Alex E.; Garrett, David J.; Cloherty, Shaun L.; Kameneva, Tatiana; Grayden, David B.; Ibbotson, Michael R.; Meffin, Hamish

2016-01-01

Implantable electrode arrays are widely used in therapeutic stimulation of the nervous system (e.g. cochlear, retinal, and cortical implants). Currently, most neural prostheses use serial stimulation (i.e. one electrode at a time) despite this severely limiting the repertoire of stimuli that can be applied. Methods to reliably predict the outcome of multi-electrode stimulation have not been available. Here, we demonstrate that a linear-nonlinear model accurately predicts neural responses to arbitrary patterns of stimulation using in vitro recordings from single retinal ganglion cells (RGCs) stimulated with a subretinal multi-electrode array. In the model, the stimulus is projected onto a low-dimensional subspace and then undergoes a nonlinear transformation to produce an estimate of spiking probability. The low-dimensional subspace is estimated using principal components analysis, which gives the neuron’s electrical receptive field (ERF), i.e. the electrodes to which the neuron is most sensitive. Our model suggests that stimulation proportional to the ERF yields a higher efficacy given a fixed amount of power when compared to equal amplitude stimulation on up to three electrodes. We find that the model captures the responses of all the cells recorded in the study, suggesting that it will generalize to most cell types in the retina. The model is computationally efficient to evaluate and, therefore, appropriate for future real-time applications including stimulation strategies that make use of recorded neural activity to improve the stimulation strategy. PMID:27035143

Local vs. volume conductance activity of field potentials in the human subthalamic nucleus

PubMed Central

Marmor, Odeya; Valsky, Dan; Joshua, Mati; Bick, Atira S; Arkadir, David; Tamir, Idit; Bergman, Hagai; Israel, Zvi

2017-01-01

Subthalamic nucleus field potentials have attracted growing research and clinical interest over the last few decades. However, it is unclear whether subthalamic field potentials represent locally generated neuronal subthreshold activity or volume conductance of the organized neuronal activity generated in the cortex. This study aimed at understanding of the physiological origin of subthalamic field potentials and determining the most accurate method for recording them. We compared different methods of recordings in the human subthalamic nucleus: spikes (300–9,000 Hz) and field potentials (3–100 Hz) recorded by monopolar micro- and macroelectrodes, as well as by differential-bipolar macroelectrodes. The recordings were done outside and inside the subthalamic nucleus during electrophysiological navigation for deep brain stimulation procedures (150 electrode trajectories) in 41 Parkinson’s disease patients. We modeled the signal and estimated the contribution of nearby/independent vs. remote/common activity in each recording configuration and area. Monopolar micro- and macroelectrode recordings detect field potentials that are considerably affected by common (probably cortical) activity. However, bipolar macroelectrode recordings inside the subthalamic nucleus can detect locally generated potentials. These results are confirmed by high correspondence between the model predictions and actual correlation of neuronal activity recorded by electrode pairs. Differential bipolar macroelectrode subthalamic field potentials can overcome volume conductance effects and reflect locally generated neuronal activity. Bipolar macroelectrode local field potential recordings might be used as a biological marker of normal and pathological brain functions for future electrophysiological studies and navigation systems as well as for closed-loop deep brain stimulation paradigms. NEW & NOTEWORTHY Our results integrate a new method for human subthalamic recordings with a development of an advanced mathematical model. We found that while monopolar microelectrode and macroelectrode recordings detect field potentials that are considerably affected by common (probably cortical) activity, bipolar macroelectrode recordings inside the subthalamic nucleus (STN) detect locally generated potentials that are significantly different than those recorded outside the STN. Differential bipolar subthalamic field potentials can be used in navigation and closed-loop deep brain stimulation paradigms. PMID:28202569

[Finite element analysis of temperature field of retina by electrical stimulation with microelectrode array].

PubMed

Wang, Wei; Qiao, Qingli; Gao, Weiping; Wu, Jun

2014-12-01

We studied the influence of electrode array parameters on temperature distribution to the retina during the use of retinal prosthesis in order to avoid thermal damage to retina caused by long-term electrical stimulation. Based on real epiretinal prosthesis, a three-dimensional model of electrical stimulation for retina with 4 X 4 microelectrode array had been established using the finite element software (COMSOL Multiphysics). The steady-state temperature field of electrical stimulation of the retina was calculated, and the effects of the electrode parameters such as the distance between the electrode contacts, the materials and area of the electrode contact on temperature field were considered. The maximum increase in the retina steady temperature was about 0. 004 degrees C with practical stimulation current. When the distance between the electrode contacts was changed from 130 microm to 520 microm, the temperature was reduced by about 0.006 microC. When the contact radius was doubled from 130 microm to 260 microm, the temperature decrease was about 0.005 degrees C. It was shown that there were little temperature changes in the retina with a 4 x 4 epiretinal microelectrode array, reflecting the safety of electrical stimulation. It was also shown that the maximum temperature in the retina decreased with increasing the distance between the electrode contacts, as well as increasing the area of electrode contact. However, the change of the maximum temperature was very small when the distance became larger than the diameter of electrode contact. There was no significant difference in the effects of temperature increase among the different electrode materials. Rational selection of the distance between the electrode contacts and their area in electrode design can reduce the temperature rise induced by electrical stimulation.

Graphene electrodes for stimulation of neuronal cells

NASA Astrophysics Data System (ADS)

Koerbitzer, Berit; Krauss, Peter; Nick, Christoph; Yadav, Sandeep; Schneider, Joerg J.; Thielemann, Christiane

2016-06-01

Graphene has the ability to improve the electrical interface between neuronal cells and electrodes used for recording and stimulation purposes. It provides a biocompatible coating for common electrode materials such as gold and improves the electrode properties. Graphene electrodes are also prepared on SiO2 substrate to benefit from its optical properties like transparency. We perform electrochemical and Raman characterization of gold electrodes with graphene coating and compare them with graphene on SiO2 substrate. It was found that the substrate plays an important role in the performance of graphene and show that graphene on SiO2 substrate is a very promising material combination for stimulation electrodes.

Exploratory study of once-daily transcranial direct current stimulation (tDCS) as a treatment for auditory hallucinations in schizophrenia.

PubMed

Fröhlich, F; Burrello, T N; Mellin, J M; Cordle, A L; Lustenberger, C M; Gilmore, J H; Jarskog, L F

2016-03-01

Auditory hallucinations are resistant to pharmacotherapy in about 25% of adults with schizophrenia. Treatment with noninvasive brain stimulation would provide a welcomed additional tool for the clinical management of auditory hallucinations. A recent study found a significant reduction in auditory hallucinations in people with schizophrenia after five days of twice-daily transcranial direct current stimulation (tDCS) that simultaneously targeted left dorsolateral prefrontal cortex and left temporo-parietal cortex. We hypothesized that once-daily tDCS with stimulation electrodes over left frontal and temporo-parietal areas reduces auditory hallucinations in patients with schizophrenia. We performed a randomized, double-blind, sham-controlled study that evaluated five days of daily tDCS of the same cortical targets in 26 outpatients with schizophrenia and schizoaffective disorder with auditory hallucinations. We found a significant reduction in auditory hallucinations measured by the Auditory Hallucination Rating Scale (F2,50=12.22, P<0.0001) that was not specific to the treatment group (F2,48=0.43, P=0.65). No significant change of overall schizophrenia symptom severity measured by the Positive and Negative Syndrome Scale was observed. The lack of efficacy of tDCS for treatment of auditory hallucinations and the pronounced response in the sham-treated group in this study contrasts with the previous finding and demonstrates the need for further optimization and evaluation of noninvasive brain stimulation strategies. In particular, higher cumulative doses and higher treatment frequencies of tDCS together with strategies to reduce placebo responses should be investigated. Additionally, consideration of more targeted stimulation to engage specific deficits in temporal organization of brain activity in patients with auditory hallucinations may be warranted. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Resting-state functional magnetic resonance imaging of the subthalamic microlesion and stimulation effects in Parkinson's disease: Indications of a principal role of the brainstem

PubMed Central

Holiga, Štefan; Mueller, Karsten; Möller, Harald E.; Urgošík, Dušan; Růžička, Evžen; Schroeter, Matthias L.; Jech, Robert

2015-01-01

During implantation of deep-brain stimulation (DBS) electrodes in the target structure, neurosurgeons and neurologists commonly observe a “microlesion effect” (MLE), which occurs well before initiating subthalamic DBS. This phenomenon typically leads to a transitory improvement of motor symptoms of patients suffering from Parkinson's disease (PD). Mechanisms behind MLE remain poorly understood. In this work, we exploited the notion of ranking to assess spontaneous brain activity in PD patients examined by resting-state functional magnetic resonance imaging in response to penetration of DBS electrodes in the subthalamic nucleus. In particular, we employed a hypothesis-free method, eigenvector centrality (EC), to reveal motor-communication-hubs of the highest rank and their reorganization following the surgery; providing a unique opportunity to evaluate the direct impact of disrupting the PD motor circuitry in vivo without prior assumptions. Penetration of electrodes was associated with increased EC of functional connectivity in the brainstem. Changes in connectivity were quantitatively related to motor improvement, which further emphasizes the clinical importance of the functional integrity of the brainstem. Surprisingly, MLE and DBS were associated with anatomically different EC maps despite their similar clinical benefit on motor functions. The DBS solely caused an increase in connectivity of the left premotor region suggesting separate pathophysiological mechanisms of both interventions. While the DBS acts at the cortical level suggesting compensatory activation of less affected motor regions, the MLE affects more fundamental circuitry as the dysfunctional brainstem predominates in the beginning of PD. These findings invigorate the overlooked brainstem perspective in the understanding of PD and support the current trend towards its early diagnosis. PMID:26509113

Resting-state functional magnetic resonance imaging of the subthalamic microlesion and stimulation effects in Parkinson's disease: Indications of a principal role of the brainstem.

PubMed

Holiga, Štefan; Mueller, Karsten; Möller, Harald E; Urgošík, Dušan; Růžička, Evžen; Schroeter, Matthias L; Jech, Robert

2015-01-01

During implantation of deep-brain stimulation (DBS) electrodes in the target structure, neurosurgeons and neurologists commonly observe a "microlesion effect" (MLE), which occurs well before initiating subthalamic DBS. This phenomenon typically leads to a transitory improvement of motor symptoms of patients suffering from Parkinson's disease (PD). Mechanisms behind MLE remain poorly understood. In this work, we exploited the notion of ranking to assess spontaneous brain activity in PD patients examined by resting-state functional magnetic resonance imaging in response to penetration of DBS electrodes in the subthalamic nucleus. In particular, we employed a hypothesis-free method, eigenvector centrality (EC), to reveal motor-communication-hubs of the highest rank and their reorganization following the surgery; providing a unique opportunity to evaluate the direct impact of disrupting the PD motor circuitry in vivo without prior assumptions. Penetration of electrodes was associated with increased EC of functional connectivity in the brainstem. Changes in connectivity were quantitatively related to motor improvement, which further emphasizes the clinical importance of the functional integrity of the brainstem. Surprisingly, MLE and DBS were associated with anatomically different EC maps despite their similar clinical benefit on motor functions. The DBS solely caused an increase in connectivity of the left premotor region suggesting separate pathophysiological mechanisms of both interventions. While the DBS acts at the cortical level suggesting compensatory activation of less affected motor regions, the MLE affects more fundamental circuitry as the dysfunctional brainstem predominates in the beginning of PD. These findings invigorate the overlooked brainstem perspective in the understanding of PD and support the current trend towards its early diagnosis.

Exploring potential social influences on brain potentials during anticipation of tactile stimulation.

PubMed

Shen, Guannan; Saby, Joni N; Drew, Ashley R; Marshall, Peter J

2017-03-15

This study explored interpersonal influences on electrophysiological responses during the anticipation of tactile stimulation. It is well-known that broad, negative-going potentials are present in the event-related potential (ERP) between a forewarning cue and a tactile stimulus. It has also been shown that the alpha-range mu rhythm shows a lateralized desynchronization over central electrode sites during anticipation of tactile stimulation of the hand. The current study used a tactile discrimination task in which a visual cue signaled that an upcoming stimulus would either be delivered 1500ms later to the participant's hand, to a task partner's hand, or to neither person. For the condition in which participants anticipated the tactile stimulation to their own hand, a negative potential (contingent negative variation, CNV) was observed in the ERP at central sites in the 1000ms prior to the tactile stimulus. Significant mu rhythm desynchronization was also present in the same time window. The magnitudes of the ERPs and of the mu desynchronization were greater in the contralateral than in the ipsilateral hemisphere prior to right hand stimulation. Similar ERP and EEG changes were not present when the visual cue indicated that stimulation would be delivered to the task partner or to neither person. The absence of social influences during anticipation of tactile stimulation, and the relationship between the two brain signatures of anticipatory attention (CNV and mu rhythm) are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Bio-inspired hybrid microelectrodes: a hybrid solution to improve long-term performance of chronic intracortical implants

PubMed Central

De Faveri, Sara; Maggiolini, Emma; Miele, Ermanno; De Angelis, Francesco; Cesca, Fabrizia; Benfenati, Fabio; Fadiga, Luciano

2014-01-01

The use of implants that allow chronic electrical stimulation and recording in the brain of human patients is currently limited by a series of events that cause the deterioration over time of both the electrode surface and the surrounding tissue. The main reason of failure is the tissue inflammatory reaction that eventually causes neuronal loss and glial encapsulation, resulting in a progressive increase of the electrode-electrolyte impedance. Here, we describe a new method to create bio-inspired electrodes to mimic the mechanical properties and biological composition of the host tissue. This combination has a great potential to increase the implant lifetime by reducing tissue reaction and improving electrical coupling. Our method implies coating the electrode with reprogrammed neural or glial cells encapsulated within a hydrogel layer. We chose fibrin as a hydrogel and primary hippocampal neurons or astrocytes from rat brain as cellular layer. We demonstrate that fibrin coating is highly biocompatible, forms uniform coatings of controllable thickness, does not alter the electrochemical properties of the microelectrode and allows good quality recordings. Moreover, it reduces the amount of host reactive astrocytes – over time – compared to a bare wire and is fully reabsorbed by the surrounding tissue within 7 days after implantation, avoiding the common problem of hydrogels swelling. Both astrocytes and neurons could be successfully grown onto the electrode surface within the fibrin hydrogel without altering the electrochemical properties of the microelectrode. This bio-hybrid device has therefore a good potential to improve the electrical integration at the neuron-electrode interface and support the long-term success of neural prostheses. PMID:24782757

Chronic Electrical Stimulation with a Suprachoroidal Retinal Prosthesis: A Preclinical Safety and Efficacy Study

PubMed Central

Nayagam, David A. X.; Williams, Richard A.; Allen, Penelope J.; Shivdasani, Mohit N.; Luu, Chi D.; Salinas-LaRosa, Cesar M.; Finch, Sue; Ayton, Lauren N.; Saunders, Alexia L.; McPhedran, Michelle; McGowan, Ceara; Villalobos, Joel; Fallon, James B.; Wise, Andrew K.; Yeoh, Jonathan; Xu, Jin; Feng, Helen; Millard, Rodney; McWade, Melanie; Thien, Patrick C.; Williams, Chris E.; Shepherd, Robert K.

2014-01-01

Purpose To assess the safety and efficacy of chronic electrical stimulation of the retina with a suprachoroidal visual prosthesis. Methods Seven normally-sighted feline subjects were implanted for 96–143 days with a suprachoroidal electrode array and six were chronically stimulated for 70–105 days at levels that activated the visual cortex. Charge balanced, biphasic, current pulses were delivered to platinum electrodes in a monopolar stimulation mode. Retinal integrity/function and the mechanical stability of the implant were assessed monthly using electroretinography (ERG), optical coherence tomography (OCT) and fundus photography. Electrode impedances were measured weekly and electrically-evoked visual cortex potentials (eEVCPs) were measured monthly to verify that chronic stimuli were suprathreshold. At the end of the chronic stimulation period, thresholds were confirmed with multi-unit recordings from the visual cortex. Randomized, blinded histological assessments were performed by two pathologists to compare the stimulated and non-stimulated retina and adjacent tissue. Results All subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. After an initial post-operative settling period, electrode arrays were mechanically stable. Mean electrode impedances were stable between 11–15 kΩ during the implantation period. Visually-evoked ERGs & OCT were normal, and mean eEVCP thresholds did not substantially differ over time. In 81 of 84 electrode-adjacent tissue samples examined, there were no discernible histopathological differences between stimulated and unstimulated tissue. In the remaining three tissue samples there were minor focal fibroblastic and acute inflammatory responses. Conclusions Chronic suprathreshold electrical stimulation of the retina using a suprachoroidal electrode array evoked a minimal tissue response and no adverse clinical or histological findings. Moreover, thresholds and electrode impedance remained stable for stimulation durations of up to 15 weeks. This study has demonstrated the safety and efficacy of suprachoroidal stimulation with charge balanced stimulus currents. PMID:24853376

Surmounting retraining limits in musicians' dystonia by transcranial stimulation.

PubMed

Furuya, Shinichi; Nitsche, Michael A; Paulus, Walter; Altenmüller, Eckart

2014-05-01

Abnormal cortical excitability is evident in various movement disorders that compromise fine motor control. Here we tested whether skilled finger movements can be restored in musicians with focal hand dystonia through behavioral training assisted by transcranial direct current stimulation to the motor cortex of both hemispheres. The bilateral motor cortices of 20 pianists (10 with focal dystonia, 10 healthy controls) were electrically stimulated noninvasively during bimanual mirrored finger movements. We found improvement in the rhythmic accuracy of sequential finger movements with the affected hand during and after cathodal stimulation over the affected cortex and simultaneous anodal stimulation over the unaffected cortex. The improvement was retained 4 days after intervention. Neither a stimulation with the reversed montage of electrodes nor sham stimulation yielded any improvement. Furthermore, the amount of improvement was positively correlated with the severity of the symptoms. Bihemispheric stimulation without concurrent motor training failed to improve fine motor control, underlining the importance of combined retraining and stimulation for restoring the dystonic symptoms. For the healthy pianists, none of the stimulation protocols enhanced movement accuracy. These results suggest a therapeutic potential of behavioral training assisted by bihemispheric, noninvasive brain stimulation in restoring fine motor control in focal dystonia. © 2014 American Neurological Association.

Chronic multisite brain recordings from a totally implantable bidirectional neural interface: experience in 5 patients with Parkinson's disease.

PubMed

Swann, Nicole C; de Hemptinne, Coralie; Miocinovic, Svjetlana; Qasim, Salman; Ostrem, Jill L; Galifianakis, Nicholas B; Luciano, Marta San; Wang, Sarah S; Ziman, Nathan; Taylor, Robin; Starr, Philip A

2018-02-01

OBJECTIVE Dysfunction of distributed neural networks underlies many brain disorders. The development of neuromodulation therapies depends on a better understanding of these networks. Invasive human brain recordings have a favorable temporal and spatial resolution for the analysis of network phenomena but have generally been limited to acute intraoperative recording or short-term recording through temporarily externalized leads. Here, the authors describe their initial experience with an investigational, first-generation, totally implantable, bidirectional neural interface that allows both continuous therapeutic stimulation and recording of field potentials at multiple sites in a neural network. METHODS Under a physician-sponsored US Food and Drug Administration investigational device exemption, 5 patients with Parkinson's disease were implanted with the Activa PC+S system (Medtronic Inc.). The device was attached to a quadripolar lead placed in the subdural space over motor cortex, for electrocorticography potential recordings, and to a quadripolar lead in the subthalamic nucleus (STN), for both therapeutic stimulation and recording of local field potentials. Recordings from the brain of each patient were performed at multiple time points over a 1-year period. RESULTS There were no serious surgical complications or interruptions in deep brain stimulation therapy. Signals in both the cortex and the STN were relatively stable over time, despite a gradual increase in electrode impedance. Canonical movement-related changes in specific frequency bands in the motor cortex were identified in most but not all recordings. CONCLUSIONS The acquisition of chronic multisite field potentials in humans is feasible. The device performance characteristics described here may inform the design of the next generation of totally implantable neural interfaces. This research tool provides a platform for translating discoveries in brain network dynamics to improved neurostimulation paradigms. Clinical trial registration no.: NCT01934296 (clinicaltrials.gov).

Impacts of selected stimulation patterns on the perception threshold in electrocutaneous stimulation

PubMed Central

2011-01-01

Background Consistency is one of the most important concerns to convey stable artificially induced sensory feedback. However, the constancy of perceived sensations cannot be guaranteed, as the artificially evoked sensation is a function of the interaction of stimulation parameters. The hypothesis of this study is that the selected stimulation parameters in multi-electrode cutaneous stimulation have significant impacts on the perception threshold. Methods The investigated parameters included the stimulated location, the number of active electrodes, the number of pulses, and the interleaved time between a pair of electrodes. Biphasic, rectangular pulses were applied via five surface electrodes placed on the forearm of 12 healthy subjects. Results Our main findings were: 1) the perception thresholds at the five stimulated locations were significantly different (p < 0.0001), 2) dual-channel simultaneous stimulation lowered the perception thresholds and led to smaller variance in perception thresholds compared to single-channel stimulation, 3) the perception threshold was inversely related to the number of pulses, and 4) the perception threshold increased with increasing interleaved time when the interleaved time between two electrodes was below 500 μs. Conclusions To maintain a consistent perception threshold, our findings indicate that dual-channel simultaneous stimulation with at least five pulses should be used, and that the interleaved time between two electrodes should be longer than 500 μs. We believe that these findings have implications for design of reliable sensory feedback codes. PMID:21306616

Optogenetic versus electrical stimulation of dopamine terminals in the nucleus accumbens reveals local modulation of presynaptic release

PubMed Central

Melchior, James R.; Ferris, Mark J.; Stuber, Garret D.; Riddle, David R.; Jones, Sara R.

2015-01-01

The nucleus accumbens is highly heterogeneous, integrating regionally distinct afferent projections and accumbal interneurons, resulting in diverse local microenvironments. Dopamine (DA) neuron terminals similarly express a heterogeneous collection of terminal receptors that modulate DA signaling. Cyclic voltammetry is often used to probe DA terminal dynamics in brain slice preparations; however, this method traditionally requires electrical stimulation to induce DA release. Electrical stimulation excites all of the neuronal processes in the stimulation field, potentially introducing simultaneous, multi-synaptic modulation of DA terminal release. We used optogenetics to selectively stimulate DA terminals and used voltammetry to compare DA responses from electrical and optical stimulation of the same area of tissue around a recording electrode. We found that with multiple pulse stimulation trains, optically stimulated DA release increasingly exceeded that of electrical stimulation. Furthermore, electrical stimulation produced inhibition of DA release across longer duration stimulations. The GABAB antagonist, CGP 55845, increased electrically stimulated DA release significantly more than light stimulated release. The nicotinic acetylcholine receptor antagonist, dihydro-β-erythroidine hydrobromide, inhibited single pulse electrically stimulated DA release while having no effect on optically stimulated DA release. Our results demonstrate that electrical stimulation introduces local multi-synaptic modulation of DA release that is absent with optogenetically targeted stimulation. PMID:26011081

Effect of Electrical Stimulation of the Suprahyoid Muscles in Brain-Injured Patients with Dysphagia.

PubMed

Beom, Jaewon; Oh, Byung-Mo; Choi, Kyoung Hyo; Kim, Won; Song, Young Jin; You, Dae Sang; Kim, Sang Jun; Han, Tai Ryoon

2015-08-01

The purpose of this study is to determine whether neuromuscular electrical stimulation of the suprahyoid muscle is effective compared to that of the infrahyoid muscle in brain-injured patients with dysphagia. A total of 132 patients with stroke, traumatic brain injury, or brain tumor in 2 university hospitals were allocated to 2 groups: those who received electrical stimulation therapy (EST) on the suprahyoid muscles (SM group, n = 66) and those who received EST with one pair of electrodes on the suprahyoid muscle and the other pair on the infrahyoid muscle (SI group, n = 66). Patients received 11.2 ± 3.4 sessions of electrical stimulation in the SM group and 11.9 ± 3.4 sessions in the SI group. The functional dysphagia scale (FDS), swallow function score (SFS), supraglottic penetration, and subglottic aspiration were measured using videofluoroscopic swallowing study. FDS scores decreased from 42.0 ± 19.1 to 32.3 ± 17.8 in the SM group and from 44.8 ± 17.4 to 32.9 ± 18.8 in the SI group by per-protocol (PP) analysis, and those decreased from 41.2 ± 20.9 to 34.5 ± 20.3 in the SM group and from 44.3 ± 19.1 to 35.7 ± 20.5 in the SI group by intention-to-treat (ITT) analysis, after electrical stimulation (p < 0.001 for each). SFSs increased from 3.3 ± 1.8 to 4.2 ± 1.6 in the SM group and from 2.8 ± 1.8 to 4.0 ± 1.8 in the SI group by PP analysis, and those increased from 3.3 ± 1.6 to 3.9 ± 1.6 in the SM group and from 2.8 ± 1.9 to 3.6 ± 2.0 in the SI group by ITT analysis, after electrical stimulation (p < 0.001, respectively). However, changes in FDS scores, SFSs, penetration, and aspiration were comparable between the SM and the SI groups. The results suggest that both SM and SI therapies induced similar improvements in swallowing function in brain-injured patients.

The polarity-dependent effects of the bilateral brain stimulation on working memory.

PubMed

Keshvari, Fatemeh; Pouretemad, Hamid-Reza; Ekhtiari, Hamed

2013-01-01

Working memory plays a critical role in cognitive processes which are central to our daily life. Neuroimaging studies have shown that one of the most important areas corresponding to the working memory is the dorsolateral prefrontal cortex (DLFPC). This study was aimed to assess whether bilateral modulation of the DLPFC using a noninvasive brain stimulation, namely transcranial direct current stimulation (tDCS), modifies the working memory function in healthy adults. In a randomized sham-controlled cross-over study, 60 subjects (30 Males) received sham and active tDCS in two subgroups (anode left/cathode right and anode right/cathode left) of the DLPFC. Subjects were presented working memory n-back task while the reaction time and accuracy were recorded. A repeated measures, mixed design ANOVA indicated a significant difference between the type of stimulation (sham vs. active) in anodal stimulation of the left DLPFC with cathodal stimulation of the right DLPFC [F(1,55)= 5.29, P=0.019], but not the inverse polarity worsened accuracy in the 2-back working memory task. There were also no statistically significant changes in speed of working memory [F(1,55)= 0.458,P=0.502] related to type or order of stimulation. The results would imply to a polarity dependence of bilateral tDCS of working memory. Left anodal/ right cathodal stimulation of DLPFC could impair working memory, while the reverser stimulation had no effect. Meaning that bilateral stimulation of DLFC would not be a useful procedure to improve working memory. Further studies are required to understand subtle effects of different tDCS stimulation/inhibition electrode positioning on the working memory.

Evaluation of the tripolar electrode stimulation method by numerical analysis and animal experiments for cochlear implants.

PubMed

Miyoshi, S; Sakajiri, M; Ifukube, T; Matsushima, J

1997-01-01

We have proposed the Tripolar Electrode Stimulation Method (TESM) which may enable us to narrow the stimulation region and to move continuously the stimulation site for the cochlear implants. We evaluated whether or not TESM works according to a theory based on numerical analysis using the auditory nerve fiber model. In this simulation, the sum of the excited model fibers were compared with the compound actions potentials obtained from animal experiments. As a result, this experiment showed that TESM could narrow a stimulation region by controlling the sum of the currents emitted from the electrodes on both sides, and continuously move a stimulation site by changing the ratio of the currents emitted from the electrodes on both sides.

Intraoperative Subcortical Fiber Mapping with Subcortico-Cortical Evoked Potentials.

PubMed

Enatsu, Rei; Kanno, Aya; Ohtaki, Shunya; Akiyama, Yukinori; Ochi, Satoko; Mikuni, Nobuhiro

2016-02-01

During brain surgery, there are difficulties associated with identifying subcortical fibers with no clear landmarks. We evaluated the usefulness of cortical evoked potentials with subcortical stimuli (subcortico-cortical evoked potential [SCEP]) in identifying subcortical fibers intraoperatively. We used SCEP to identify the pyramidal tract in 4 patients, arcuate fasciculus in 1 patient, and both in 2 patients during surgical procedures. After resection, a 1 × 4-electrode plate was placed on the floor of the removal cavity and 1-Hz alternating electrical stimuli were delivered to this electrode. A 4 × 5 recording electrode plate was placed on the central cortical areas to map the pyramidal tract and temporoparietal cortical areas for the arcuate fasciculus. SCEPs were obtained by averaging electrocorticograms time locked to the stimulus onset. The subcortical stimulation within 15 mm of the target fiber induced cortical evoked potentials in the corresponding areas, whereas the stimulation apart from 20 mm did not. Five patients showed transient worsening of neurologic symptoms after surgery. However, all patients recovered. SCEP was useful for identifying subcortical fibers and confirmed the preservation of these fibers. This technique is expected to contribute to the effectiveness and safety of resective surgery in patients with lesions close to eloquent areas. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of prefrontal bipolar and high-definition transcranial direct current stimulation on cortical reactivity and working memory in healthy adults.

PubMed

Hill, Aron T; Rogasch, Nigel C; Fitzgerald, Paul B; Hoy, Kate E

2017-05-15

Transcranial direct current stimulation (tDCS) is a well-recognised neuromodulatory technology which has been shown to induce short-lasting changes in motor-cortical excitability. The recent and rapid expansion of tDCS into the cognitive domain, however, necessitates deeper mechanistic understanding of its neurophysiological effects over non-motor brain regions. The present study utilised transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) to probe the immediate and longer-term effects of both a bipolar (BP-tDCS) and more focal 4×1 High-Definition tDCS (HD-tDCS) montage applied over the left DLPFC on TMS-evoked potentials (TEPs) and oscillations in 19 healthy adult participants. 2-back working memory (WM) performance was also assessed as a marker of cognitive function. Region of interest (ROI) analyses taken from the F1 electrode directly adjacent to the stimulation site revealed increased P60 TEP amplitudes at this location 5min following BP-tDCS and 30min following HD-tDCS. Further global cluster based analyses of all scalp electrodes revealed widespread neuromodulatory changes following HD-tDCS, but not BP-tDCS, both five and 30min after stimulation, with reductions also detected in both beta and gamma oscillatory power over parieto-occipital channels 30min after stimulation. No significant changes in WM performance were observed following either HD-tDCS or BP-tDCS. This study highlights the capacity for single-session prefrontal anodal tDCS montages to modulate neurophysiological processes, as assessed with TMS-EEG. Copyright © 2017 Elsevier Inc. All rights reserved.

A versatile all-channel stimulator for electrode arrays, with real-time control

PubMed Central

Wagenaar, Daniel A; Potter, Steve M

2008-01-01

Over the last few decades, technology to record through ever increasing numbers of electrodes has become available to electrophysiologists. For the study of distributed neural processing, however, the ability to stimulate through equal numbers of electrodes, and thus to attain bidirectional communication, is of paramount importance. Here, we present a stimulation system for multi-electrode arrays which interfaces with existing commercial recording hardware, and allows stimulation through any electrode in the array, with rapid switching between channels. The system is controlled through real-time Linux, making it extremely flexible: stimulation sequences can be constructed on-the-fly, and arbitrary stimulus waveforms can be used if desired. A key feature of this design is that it can be readily and inexpensively reproduced in other labs, since it interfaces to standard PC parallel ports and uses only off-the-shelf components. Moreover, adaptation for use with in vivo multi-electrode probes would be straightforward. In combination with our freely available data-acquisition software, MeaBench, this system can provide feedback stimulation in response to recorded action potentials within 15 ms. PMID:15876621

Lateral hypothalamic area deep brain stimulation for refractory obesity: a pilot study with preliminary data on safety, body weight, and energy metabolism

PubMed Central

Whiting, Donald M.; Tomycz, Nestor D.; Bailes, Julian; De Jonge, Lilian; Lecoultre, Virgile; Wilent, Bryan; Alcindor, Dunbar; Prostko, E. Richard; Cheng, Boyle C.; Angle, Cynthia; Cantella, Diane; Whiting, Benjamin B.; Mizes, J. Scott; Finnis, Kirk W.; Ravussin, Eric; Oh, Michael Y.

2017-01-01

Object Deep brain stimulation (DBS) of the lateral hypothalamic area (LHA) has been suggested as a potential treatment for intractable obesity. The authors present the 2-year safety results as well as early efficacy and metabolic effects in 3 patients undergoing bilateral LHA DBS in the first study of this approach in humans. Methods Three patients meeting strict criteria for intractable obesity, including failed bariatric surgery, under-went bilateral implantation of LHA DBS electrodes as part of an institutional review board– and FDA-approved pilot study. The primary focus of the study was safety; however, the authors also received approval to collect data on early efficacy including weight change and energy metabolism. Results No serious adverse effects, including detrimental psychological consequences, were observed with continuous LHA DBS after a mean follow-up of 35 months (range 30–39 months). Three-dimensional nonlinear transformation of postoperative imaging superimposed onto brain atlas anatomy was used to confirm and study DBS contact proximity to the LHA. No significant weight loss trends were seen when DBS was programmed using standard settings derived from movement disorder DBS surgery. However, promising weight loss trends have been observed when monopolar DBS stimulation has been applied via specific contacts found to increase the resting metabolic rate measured in a respiratory chamber. Conclusions Deep brain stimulation of the LHA may be applied safely to humans with intractable obesity. Early evidence for some weight loss under metabolically optimized settings provides the first “proof of principle” for this novel antiobesity strategy. A larger follow-up study focused on efficacy along with a more rigorous metabolic analysis is planned to further explore the benefits and therapeutic mechanism behind this investigational therapy. PMID:23560573

Deep brain stimulation of the ventral hippocampus restores deficits in processing of auditory evoked potentials in a rodent developmental disruption model of schizophrenia.

PubMed

Ewing, Samuel G; Grace, Anthony A

2013-02-01

Existing antipsychotic drugs are most effective at treating the positive symptoms of schizophrenia but their relative efficacy is low and they are associated with considerable side effects. In this study deep brain stimulation of the ventral hippocampus was performed in a rodent model of schizophrenia (MAM-E17) in an attempt to alleviate one set of neurophysiological alterations observed in this disorder. Bipolar stimulating electrodes were fabricated and implanted, bilaterally, into the ventral hippocampus of rats. High frequency stimulation was delivered bilaterally via a custom-made stimulation device and both spectral analysis (power and coherence) of resting state local field potentials and amplitude of auditory evoked potential components during a standard inhibitory gating paradigm were examined. MAM rats exhibited alterations in specific components of the auditory evoked potential in the infralimbic cortex, the core of the nucleus accumbens, mediodorsal thalamic nucleus, and ventral hippocampus in the left hemisphere only. DBS was effective in reversing these evoked deficits in the infralimbic cortex and the mediodorsal thalamic nucleus of MAM-treated rats to levels similar to those observed in control animals. In contrast stimulation did not alter evoked potentials in control rats. No deficits or stimulation-induced alterations were observed in the prelimbic and orbitofrontal cortices, the shell of the nucleus accumbens or ventral tegmental area. These data indicate a normalization of deficits in generating auditory evoked potentials induced by a developmental disruption by acute high frequency, electrical stimulation of the ventral hippocampus. Copyright © 2012 Elsevier B.V. All rights reserved.

Deep brain stimulation of the ventral hippocampus restores deficits in processing of auditory evoked potentials in a rodent developmental disruption model of schizophrenia

PubMed Central

Ewing, Samuel G.; Grace, Anthony A.

2012-01-01

Existing antipsychotic drugs are most effective at treating the positive symptoms of schizophrenia, but their relative efficacy is low and they are associated with considerable side effects. In this study deep brain stimulation of the ventral hippocampus was performed in a rodent model of schizophrenia (MAM-E17) in an attempt to alleviate one set of neurophysiological alterations observed in this disorder. Bipolar stimulating electrodes were fabricated and implanted, bilaterally, into the ventral hippocampus of rats. High frequency stimulation was delivered bilaterally via a custom-made stimulation device and both spectral analysis (power and coherence) of resting state local field potentials and amplitude of auditory evoked potential components during a standard inhibitory gating paradigm were examined. MAM rats exhibited alterations in specific components of the auditory evoked potential in the infralimbic cortex, the core of the nucleus accumbens, mediodorsal thalamic nucleus, and ventral hippocampus in the left hemisphere only. DBS was effective in reversing these evoked deficits in the infralimbic cortex and the mediodorsal thalamic nucleus of MAM-treated rats to levels similar to those observed in control animals. In contrast stimulation did not alter evoked potentials in control rats. No deficits or stimulation-induced alterations were observed in the prelimbic and orbitofrontal cortices, the shell of the nucleus accumbens or ventral tegmental area. These data indicate a normalization of deficits in generating auditory evoked potentials induced by a developmental disruption by acute high frequency, electrical stimulation of the ventral hippocampus. PMID:23269227

Auditory brainstem activity and development evoked by apical versus basal cochlear implant electrode stimulation in children.

PubMed

Gordon, K A; Papsin, B C; Harrison, R V

2007-08-01

The role of apical versus basal cochlear implant electrode stimulation on central auditory development was examined. We hypothesized that, in children with early onset deafness, auditory development evoked by basal electrode stimulation would differ from that evoked more apically. Responses of the auditory nerve and brainstem, evoked by an apical and a basal implant electrode, were measured over the first year of cochlear implant use in 50 children with early onset severe to profound deafness who used hearing aids prior to implantation. Responses at initial stimulation were of larger amplitude and shorter latency when evoked by the apical electrode. No significant effects of residual hearing or age were found on initial response amplitudes or latencies. With implant use, responses evoked by both electrodes showed decreases in wave and interwave latencies reflecting decreased neural conduction time through the brainstem. Apical versus basal differences persisted with implant experience with one exception; eIII-eV interlatency differences decreased with implant use. Acute stimulation shows prolongation of basally versus apically evoked auditory nerve and brainstem responses in children with severe to profound deafness. Interwave latencies reflecting neural conduction along the caudal and rostral portions of the brainstem decreased over the first year of implant use. Differences in neural conduction times evoked by apical versus basal electrode stimulation persisted in the caudal but not rostral brainstem. Activity-dependent changes of the auditory brainstem occur in response to both apical and basal cochlear implant electrode stimulation.

In Vivo Recording of Single-Unit Activity during Singing in Zebra Finches

PubMed Central

Okubo, Tatsuo S.; Mackevicius, Emily L.; Fee, Michale S.

2015-01-01

The zebra finch is an important model for investigating the neural mechanisms that underlie vocal production and learning. Previous anatomical and gene expression studies have identified an interconnected set of brain areas in this organism that are important for singing. To advance our understanding of how these various brain areas act together to learn and produce a highly stereotyped song, it is necessary to record the activity of individual neurons during singing. Here, we present a protocol for recording single-unit activity in freely moving zebra finches during singing using a miniature, motorized microdrive. It includes procedures for both the microdrive implant surgery and the electrophysiological recordings. There are several advantages of this technique: (1) high-impedance electrodes can be used in the microdrive to obtain well-isolated single units; (2) a motorized microdrive is used to remotely control the electrode position, allowing neurons to be isolated without handling the bird, and (3) a lateral positioner is used to move electrodes into fresh tissue before each penetration, allowing recordings from well-isolated neurons over the course of several weeks. We also describe the application of the antidromic stimulation and the spike collision test to identify neurons based on the axonal projection patterns. PMID:25342072

The Mechanism of Extracellular Stimulation of Nerve Cells on an Electrolyte-Oxide-Semiconductor Capacitor

PubMed Central

Schoen, Ingmar; Fromherz, Peter

2007-01-01

Extracellular excitation of neurons is applied in studies of cultured networks and brain tissue, as well as in neuroprosthetics. We elucidate its mechanism in an electrophysiological approach by comparing voltage-clamp and current-clamp recordings of individual neurons on an insulated planar electrode. Noninvasive stimulation of neurons from pedal ganglia of Lymnaea stagnalis is achieved by defined voltage ramps applied to an electrolyte/HfO2/silicon capacitor. Effects on the smaller attached cell membrane and the larger free membrane are distinguished in a two-domain-stimulation model. Under current-clamp, we study the polarization that is induced for closed ion channels. Under voltage-clamp, we determine the capacitive gating of ion channels in the attached membrane by falling voltage ramps and for comparison also the gating of all channels by conventional variation of the intracellular voltage. Neuronal excitation is elicited under current-clamp by two mechanisms: Rising voltage ramps depolarize the free membrane such that an action potential is triggered. Falling voltage ramps depolarize the attached membrane such that local ion currents are activated that depolarize the free membrane and trigger an action potential. The electrophysiological analysis of extracellular stimulation in the simple model system is a basis for its systematic optimization in neuronal networks and brain tissue. PMID:17098803

The Effect of a Transcranial Channel as a Skull/Brain Interface in High-Definition Transcranial Direct Current Stimulation—A Computational Study

PubMed Central

Seo, Hyeon; Kim, Hyoung-Ihl; Jun, Sung Chan

2017-01-01

A transcranial channel is an interface between the skull and brain; it consists of a biocompatible and highly conductive material that helps convey the current induced by transcranial direct current stimulation (tDCS) to the target area. However, it has been proposed only conceptually, and there has been no concrete study of its efficacy. In this work, we conducted a computational investigation of this conceptual transcranial model with high-definition tDCS, inducing focalized neuromodulation to determine whether inclusion of a transcranial channel performs effectively. To do so, we constructed an anatomically realistic head model and compartmental pyramidal neuronal models. We analyzed membrane polarization by extracellular stimulation and found that the inclusion of a transcranial channel induced polarization at the target area 11 times greater than conventional HD-tDCS without the transcranial channel. Furthermore, the stimulation effect of the transcranial channel persisted up to approximately 80%, even when the stimulus electrodes were displaced approximately 5 mm from the target area. We investigated the efficacy of the transcranial channel and found that greatly improved stimulation intensity and focality may be achieved. Thus, the use of these channels may be promising for clinical treatment. PMID:28084429

Assessment of anodal and cathodal transcranial direct current stimulation (tDCS) on MMN-indexed auditory sensory processing.

PubMed

Impey, Danielle; de la Salle, Sara; Knott, Verner

2016-06-01

Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation which uses a very weak constant current to temporarily excite (anodal stimulation) or inhibit (cathodal stimulation) activity in the brain area of interest via small electrodes placed on the scalp. Currently, tDCS of the frontal cortex is being used as a tool to investigate cognition in healthy controls and to improve symptoms in neurological and psychiatric patients. tDCS has been found to facilitate cognitive performance on measures of attention, memory, and frontal-executive functions. Recently, a short session of anodal tDCS over the temporal lobe has been shown to increase auditory sensory processing as indexed by the Mismatch Negativity (MMN) event-related potential (ERP). This preliminary pilot study examined the separate and interacting effects of both anodal and cathodal tDCS on MMN-indexed auditory pitch discrimination. In a randomized, double blind design, the MMN was assessed before (baseline) and after tDCS (2mA, 20min) in 2 separate sessions, one involving 'sham' stimulation (the device is turned off), followed by anodal stimulation (to temporarily excite cortical activity locally), and one involving cathodal stimulation (to temporarily decrease cortical activity locally), followed by anodal stimulation. Results demonstrated that anodal tDCS over the temporal cortex increased MMN-indexed auditory detection of pitch deviance, and while cathodal tDCS decreased auditory discrimination in baseline-stratified groups, subsequent anodal stimulation did not significantly alter MMN amplitudes. These findings strengthen the position that tDCS effects on cognition extend to the neural processing of sensory input and raise the possibility that this neuromodulatory technique may be useful for investigating sensory processing deficits in clinical populations. Copyright © 2016 Elsevier Inc. All rights reserved.

Communication calls produced by electrical stimulation of four structures in the guinea pig brain

PubMed Central

Green, David B.; Shackleton, Trevor M.; Grimsley, Jasmine M. S.; Zobay, Oliver; Palmer, Alan R.

2018-01-01

One of the main central processes affecting the cortical representation of conspecific vocalizations is the collateral output from the extended motor system for call generation. Before starting to study this interaction we sought to compare the characteristics of calls produced by stimulating four different parts of the brain in guinea pigs (Cavia porcellus). By using anaesthetised animals we were able to reposition electrodes without distressing the animals. Trains of 100 electrical pulses were used to stimulate the midbrain periaqueductal grey (PAG), hypothalamus, amygdala, and anterior cingulate cortex (ACC). Each structure produced a similar range of calls, but in significantly different proportions. Two of the spontaneous calls (chirrup and purr) were never produced by electrical stimulation and although we identified versions of chutter, durr and tooth chatter, they differed significantly from our natural call templates. However, we were routinely able to elicit seven other identifiable calls. All seven calls were produced both during the 1.6 s period of stimulation and subsequently in a period which could last for more than a minute. A single stimulation site could produce four or five different calls, but the amygdala was much less likely to produce a scream, whistle or rising whistle than any of the other structures. These three high-frequency calls were more likely to be produced by females than males. There were also differences in the timing of the call production with the amygdala primarily producing calls during the electrical stimulation and the hypothalamus mainly producing calls after the electrical stimulation. For all four structures a significantly higher stimulation current was required in males than females. We conclude that all four structures can be stimulated to produce fictive vocalizations that should be useful in studying the relationship between the vocal motor system and cortical sensory representation. PMID:29584746

Communication calls produced by electrical stimulation of four structures in the guinea pig brain.

PubMed

Green, David B; Shackleton, Trevor M; Grimsley, Jasmine M S; Zobay, Oliver; Palmer, Alan R; Wallace, Mark N

2018-01-01

One of the main central processes affecting the cortical representation of conspecific vocalizations is the collateral output from the extended motor system for call generation. Before starting to study this interaction we sought to compare the characteristics of calls produced by stimulating four different parts of the brain in guinea pigs (Cavia porcellus). By using anaesthetised animals we were able to reposition electrodes without distressing the animals. Trains of 100 electrical pulses were used to stimulate the midbrain periaqueductal grey (PAG), hypothalamus, amygdala, and anterior cingulate cortex (ACC). Each structure produced a similar range of calls, but in significantly different proportions. Two of the spontaneous calls (chirrup and purr) were never produced by electrical stimulation and although we identified versions of chutter, durr and tooth chatter, they differed significantly from our natural call templates. However, we were routinely able to elicit seven other identifiable calls. All seven calls were produced both during the 1.6 s period of stimulation and subsequently in a period which could last for more than a minute. A single stimulation site could produce four or five different calls, but the amygdala was much less likely to produce a scream, whistle or rising whistle than any of the other structures. These three high-frequency calls were more likely to be produced by females than males. There were also differences in the timing of the call production with the amygdala primarily producing calls during the electrical stimulation and the hypothalamus mainly producing calls after the electrical stimulation. For all four structures a significantly higher stimulation current was required in males than females. We conclude that all four structures can be stimulated to produce fictive vocalizations that should be useful in studying the relationship between the vocal motor system and cortical sensory representation.

Deep brain stimulation of the anterior internal capsule for the treatment of Tourette syndrome: technical case report.

PubMed

Flaherty, Alice W; Williams, Ziv M; Amirnovin, Ramin; Kasper, Ekkehard; Rauch, Scott L; Cosgrove, G Rees; Eskandar, Emad N

2005-10-01

Medical treatment of Tourette syndrome is often ineffective or is accompanied by debilitating side effects, therefore prompting the need to evaluate surgical therapies. We present the case of a 37-year-old woman with severe Tourette syndrome since the age of 10 years. Her symptoms included frequent vocalizations and severe head and arm jerks that resulted in unilateral blindness. Trials of more than 40 medications and other therapies had failed to relieve the tics. We implanted bilateral electrodes in the anterior limb of the internal capsule, terminating in the vicinity of the nucleus accumbens. At 18-month follow-up, optimal stimulation continued to lower her tic frequency and severity significantly. Our findings suggest that stimulation of the anterior internal capsule may be a safe and effective procedure for the treatment of Tourette syndrome.

Different Movement of Hyolaryngeal Structures by Various Application of Electrical Stimulation in Normal Individuals

PubMed Central

Kim, Sae Hyun; Oh, Byung-Mo; Han, Tae Ryun; Jeong, Ho Joong

2015-01-01

Objective To identify the differences in the movement of the hyoid bone and the vocal cord with and without electrical stimulation in normal subjects. Methods Two-dimensional motion analysis using a videofluoroscopic swallowing study with and without electrical stimulation was performed. Surface electrical stimulation was applied during swallowing using electrodes placed at three different locations on each subject. All subjects were analyzed three times using the following electrode placements: with one pair of electrodes on the suprahyoid muscles and a second pair on the infrahyoid muscles (SI); with placement of the electrode pairs on only the infrahyoid muscles (IO); and with the electrode pairs placed vertically on the suprahyoid and infrahyoid muscles (SIV). Results The main outcomes of this study demonstrated an initial downward displacement as well as different movements of the hyoid bone with the three electrode placements used for electrical stimulation. The initial positions of the hyoid bone with the SI and IO placements resulted in an inferior and anterior displaced position. During swallowing, the hyoid bone moved in a more superior and less anterior direction, resulting in almost the same peak position compared with no electrical stimulation. Conclusion These results demonstrate that electrical stimulation caused an initial depression of the hyoid bone, which had nearly the same peak position during swallowing. Electrical stimulation during swallowing was not dependent on the position of the electrode on the neck, such as on the infrahyoid or on both the suprahyoid and infrahyoid muscles. PMID:26361589

An energy-efficient, adiabatic electrode stimulator with inductive energy recycling and feedback current regulation.

PubMed

Arfin, Scott K; Sarpeshkar, Rahul

2012-02-01

In this paper, we present a novel energy-efficient electrode stimulator. Our stimulator uses inductive storage and recycling of energy in a dynamic power supply. This supply drives an electrode in an adiabatic fashion such that energy consumption is minimized. It also utilizes a shunt current-sensor to monitor and regulate the current through the electrode via feedback, thus enabling flexible and safe stimulation. Since there are no explicit current sources or current limiters, wasteful energy dissipation across such elements is naturally avoided. The dynamic power supply allows efficient transfer of energy both to and from the electrode and is based on a DC-DC converter topology that we use in a bidirectional fashion in forward-buck or reverse-boost modes. In an exemplary electrode implementation intended for neural stimulation, we show how the stimulator combines the efficiency of voltage control and the safety and accuracy of current control in a single low-power integrated-circuit built in a standard .35 μm CMOS process. This stimulator achieves a 2x-3x reduction in energy consumption as compared to a conventional current-source-based stimulator operating from a fixed power supply. We perform a theoretical analysis of the energy efficiency that is in accord with experimental measurements. This theoretical analysis reveals that further improvements in energy efficiency may be achievable with better implementations in the future. Our electrode stimulator could be widely useful for neural, cardiac, retinal, cochlear, muscular and other biomedical implants where low power operation is important.

Deep brain stimulation for Parkinson's disease: defining the optimal location within the subthalamic nucleus.

PubMed

Bot, Maarten; Schuurman, P Richard; Odekerken, Vincent J J; Verhagen, Rens; Contarino, Fiorella Maria; De Bie, Rob M A; van den Munckhof, Pepijn

2018-05-01

Individual motor improvement after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD) varies considerably. Stereotactic targeting of the dorsolateral sensorimotor part of the STN is considered paramount for maximising effectiveness, but studies employing the midcommissural point (MCP) as anatomical reference failed to show correlation between DBS location and motor improvement. The medial border of the STN as reference may provide better insight in the relationship between DBS location and clinical outcome. Motor improvement after 12 months of 65 STN DBS electrodes was categorised into non-responding, responding and optimally responding body-sides. Stereotactic coordinates of optimal electrode contacts relative to both medial STN border and MCP served to define theoretic DBS 'hotspots'. Using the medial STN border as reference, significant negative correlation (Pearson's correlation -0.52, P<0.01) was found between the Euclidean distance from the centre of stimulation to this DBS hotspot and motor improvement. This hotspot was located at 2.8 mm lateral, 1.7 mm anterior and 2.5 mm superior relative to the medial STN border. Using MCP as reference, no correlation was found. The medial STN border proved superior compared with MCP as anatomical reference for correlation of DBS location and motor improvement, and enabled defining an optimal DBS location within the nucleus. We therefore propose the medial STN border as a better individual reference point than the currently used MCP on preoperative stereotactic imaging, in order to obtain optimal and thus less variable motor improvement for individual patients with PD following STN DBS. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Regenerated Sciatic Nerve Axons Stimulated through a Chronically Implanted Macro-Sieve Electrode.

PubMed

MacEwan, Matthew R; Zellmer, Erik R; Wheeler, Jesse J; Burton, Harold; Moran, Daniel W

2016-01-01

Sieve electrodes provide a chronic interface for stimulating peripheral nerve axons. Yet, successful utilization requires robust axonal regeneration through the implanted electrode. The present study determined the effect of large transit zones in enhancing axonal regeneration and revealed an intimate neural interface with an implanted sieve electrode. Fabrication of the polyimide sieve electrodes employed sacrificial photolithography. The manufactured macro-sieve electrode (MSE) contained nine large transit zones with areas of ~0.285 mm 2 surrounded by eight Pt-Ir metallized electrode sites. Prior to implantation, saline, or glial derived neurotropic factor (GDNF) was injected into nerve guidance silicone-conduits with or without a MSE. The MSE assembly or a nerve guidance conduit was implanted between transected ends of the sciatic nerve in adult male Lewis rats. At 3 months post-operation, fiber counts were similar through both implant types. Likewise, stimulation of nerves regenerated through a MSE or an open silicone conduit evoked comparable muscle forces. These results showed that nerve regeneration was comparable through MSE transit zones and an open conduit. GDNF had a minimal positive effect on the quality and morphology of fibers regenerating through the MSE; thus, the MSE may reduce reliance on GDNF to augment axonal regeneration. Selective stimulation of several individual muscles was achieved through monopolar stimulation of individual electrodes sites suggesting that the MSE might be an optimal platform for functional neuromuscular stimulation.

Regenerated Sciatic Nerve Axons Stimulated through a Chronically Implanted Macro-Sieve Electrode

PubMed Central

MacEwan, Matthew R.; Zellmer, Erik R.; Wheeler, Jesse J.; Burton, Harold; Moran, Daniel W.

2016-01-01

Sieve electrodes provide a chronic interface for stimulating peripheral nerve axons. Yet, successful utilization requires robust axonal regeneration through the implanted electrode. The present study determined the effect of large transit zones in enhancing axonal regeneration and revealed an intimate neural interface with an implanted sieve electrode. Fabrication of the polyimide sieve electrodes employed sacrificial photolithography. The manufactured macro-sieve electrode (MSE) contained nine large transit zones with areas of ~0.285 mm2 surrounded by eight Pt-Ir metallized electrode sites. Prior to implantation, saline, or glial derived neurotropic factor (GDNF) was injected into nerve guidance silicone-conduits with or without a MSE. The MSE assembly or a nerve guidance conduit was implanted between transected ends of the sciatic nerve in adult male Lewis rats. At 3 months post-operation, fiber counts were similar through both implant types. Likewise, stimulation of nerves regenerated through a MSE or an open silicone conduit evoked comparable muscle forces. These results showed that nerve regeneration was comparable through MSE transit zones and an open conduit. GDNF had a minimal positive effect on the quality and morphology of fibers regenerating through the MSE; thus, the MSE may reduce reliance on GDNF to augment axonal regeneration. Selective stimulation of several individual muscles was achieved through monopolar stimulation of individual electrodes sites suggesting that the MSE might be an optimal platform for functional neuromuscular stimulation. PMID:28008303

A comparison of two surgical approaches in functional neurosurgery: individualized versus conventional stereotactic frames.

PubMed

Matzke, Cornelia; Lindner, Dirk; Schwarz, Johannes; Classen, Joseph; Hammer, Niels; Weise, David; Rumpf, Jost-Julian; Fritzsch, Dominik; Meixensberger, Jürgen; Winkler, Dirk

2015-01-01

The individualized Starfix® miniframe belongs to a new generation of stereotactic systems enabling high-precision electrode placement with considerably better time-efficiency in deep brain stimulation (DBS). We evaluated the usability and reliability of this novel technique in patients with idiopathic Parkinson's disease (IPD) and compared surgical and clinical results with those obtained in a historical group in which a conventional stereotactic frame was employed. Sixty patients underwent surgery for implantation of DBS electrodes in the subthalamic nucleus. In 31 of them (group I) a conventional Zamorano-Dujovny frame was used and in 29 of them (group II) a Starfix® miniframe was used. Image fusion of preoperatively acquired 3D T1w and T2w 1.5 T MR-image series was used for the targeting procedure. Placement of the test electrodes and permanent electrodes corresponded to standard functional neurosurgery and included microelectrode recording and macrostimulation. Clinical (L-Dopa equivalent dose, United Parkinson's disease rating scale part III) and time for surgical electrode implantation were evaluated postoperatively in a 3-, 6- and 12-month follow-up. Twelve months postoperatively, L-Dopa dose was significantly reduced from 685.19 to 205.88 mg/day and from 757.92 to 314.42 mg/day in groups I and II, respectively. A comparable reduction of the LED could be observed 1 year after surgery. Motor function has improved in a significant and identical manner with 59% (group I) and 61% (group II). Besides clinical effects by stimulation therapy there was a significantly reduced surgery time required for electrode implantation using the Starfix® miniframe (group I: 234.1 min, group II: 173.6 min; p < 0.001). Individualized miniframes such as the Starfix® miniframe allow implantation of DBS electrodes in IPD that is equally effective as conventional systems. The time efficiency achieved in surgery using of the Starfix® system helps to minimize patients' discomfort during DBS surgery.

Technological Advances in Deep Brain Stimulation.

PubMed

Ughratdar, Ismail; Samuel, Michael; Ashkan, Keyoumars

2015-01-01

Functional and stereotactic neurosurgery has always been regarded as a subspecialty based on and driven by technological advances. However until recently, the fundamentals of deep brain stimulation (DBS) hardware and software design had largely remained stagnant since its inception almost three decades ago. Recent improved understanding of disease processes in movement disorders as well clinician and patient demands has resulted in new avenues of development for DBS technology. This review describes new advances both related to hardware and software for neuromodulation. New electrode designs with segmented contacts now enable sophisticated shaping and sculpting of the field of stimulation, potentially allowing multi-target stimulation and avoidance of side effects. To avoid lengthy programming sessions utilising multiple lead contacts, new user-friendly software allows for computational modelling and individualised directed programming. Therapy delivery is being improved with the next generation of smaller profile, longer-lasting, re-chargeable implantable pulse generators (IPGs). These include IPGs capable of delivering constant current stimulation or personalised closed-loop adaptive stimulation. Post-implantation Magnetic Resonance Imaging (MRI) has long been an issue which has been partially overcome with 'MRI conditional devices' and has enabled verification of DBS lead location. Surgical technique is considering a shift from frame-based to frameless stereotaxy or greater role for robot assisted implantation. The challenge for these contemporary techniques however, will be in demonstrating equivalent safety and accuracy to conventional methods. We also discuss potential future direction utilising wireless technology allowing for miniaturisation of hardware.

Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation.

PubMed

Rangarajan, Vinitha; Parvizi, Josef

2016-03-01

The ventral temporal cortex (VTC) contains several areas with selective responses to words, numbers, faces, and objects as demonstrated by numerous human and primate imaging and electrophysiological studies. Our recent work using electrocorticography (ECoG) confirmed the presence of face-selective neuronal populations in the human fusiform gyrus (FG) in patients implanted with intracranial electrodes in either the left or right hemisphere. Electrical brain stimulation (EBS) disrupted the conscious perception of faces only when it was delivered in the right, but not left, FG. In contrast to our previous findings, here we report both negative and positive EBS effects in right and left FG, respectively. The presence of right hemisphere language dominance in the first, and strong left-handedness and poor language processing performance in the second case, provide indirect clues about the functional architecture of the human VTC in relation to hemispheric asymmetries in language processing and handedness. Copyright © 2015 Elsevier Ltd. All rights reserved.

Electrical stimulation of the brain and the development of cortical visual prostheses: An historical perspective.

PubMed

Lewis, Philip M; Rosenfeld, Jeffrey V

2016-01-01

Rapid advances are occurring in neural engineering, bionics and the brain-computer interface. These milestones have been underpinned by staggering advances in micro-electronics, computing, and wireless technology in the last three decades. Several cortically-based visual prosthetic devices are currently being developed, but pioneering advances with early implants were achieved by Brindley followed by Dobelle in the 1960s and 1970s. We have reviewed these discoveries within the historical context of the medical uses of electricity including attempts to cure blindness, the discovery of the visual cortex, and opportunities for cortex stimulation experiments during neurosurgery. Further advances were made possible with improvements in electrode design, greater understanding of cortical electrophysiology and miniaturisation of electronic components. Human trials of a new generation of prototype cortical visual prostheses for the blind are imminent. This article is part of a Special Issue entitled Hold Item. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Comparison of magnetic resonance imaging sequences for depicting the subthalamic nucleus for deep brain stimulation.

PubMed

Nagahama, Hiroshi; Suzuki, Kengo; Shonai, Takaharu; Aratani, Kazuki; Sakurai, Yuuki; Nakamura, Manami; Sakata, Motomichi

2015-01-01

Electrodes are surgically implanted into the subthalamic nucleus (STN) of Parkinson's disease patients to provide deep brain stimulation. For ensuring correct positioning, the anatomic location of the STN must be determined preoperatively. Magnetic resonance imaging has been used for pinpointing the location of the STN. To identify the optimal imaging sequence for identifying the STN, we compared images produced with T2 star-weighted angiography (SWAN), gradient echo T2*-weighted imaging, and fast spin echo T2-weighted imaging in 6 healthy volunteers. Our comparison involved measurement of the contrast-to-noise ratio (CNR) for the STN and substantia nigra and a radiologist's interpretations of the images. Of the sequences examined, the CNR and qualitative scores were significantly higher on SWAN images than on other images (p < 0.01) for STN visualization. Kappa value (0.74) on SWAN images was the highest in three sequences for visualizing the STN. SWAN is the sequence best suited for identifying the STN at the present time.

Electromagnetic Field Modeling of Transcranial Electric and Magnetic Stimulation: Targeting, Individualization, and Safety of Convulsive and Subconvulsive Applications

NASA Astrophysics Data System (ADS)

Deng, Zhi-De

The proliferation of noninvasive transcranial electric and magnetic brain stimulation techniques and applications in recent years has led to important insights into brain function and pathophysiology of brain-based disorders. Transcranial electric and magnetic stimulation encompasses a wide spectrum of methods that have developed into therapeutic interventions for a variety of neurological and psychiatric disorders. Although these methods are at different stages of development, the physical principle underlying these techniques is the similar. Namely, an electromagnetic field is induced in the brain either via current injection through scalp electrodes or via electromagnetic induction. The induced electric field modulates the neuronal transmembrane potentials and, thereby, neuronal excitability or activity. Therefore, knowledge of the induced electric field distribution is key in the design and interpretation of basic research and clinical studies. This work aims to delineate the fundamental physical limitations, tradeoffs, and technological feasibility constraints associated with transcranial electric and magnetic stimulation, in order to inform the development of technologies that deliver safer, and more spatially, temporally, and patient specific stimulation. Part I of this dissertation expounds on the issue of spatial targeting of the electric field. Contrasting electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) configurations that differ markedly in efficacy, side effects, and seizure induction efficiency could advance our understanding of the principles linking treatment parameters and therapeutic outcome and could provide a means of testing hypotheses of the mechanisms of therapeutic action. Using the finite element method, we systematically compare the electric field characteristics of existing forms of ECT and MST. We introduce a method of incorporating a modality-specific neural activation threshold in the electric field models that can inform dosage requirements in convulsive therapies. Our results indicate that the MST electric field is more focal and more confined to the superficial cortex compared to ECT. Further, the conventional ECT current amplitude is much higher than necessary for seizure induction. One of the factors important to clinical outcome is seizure expression. However, it is unknown how the induced electric field is related to seizure onset and propagation. In this work, we explore the effect of the electric field distribution on the quantitative ictal electroencephalography and current source density in ECT and MST. We further demonstrate how the ECT electrode shape, size, spacing, and current can be manipulated to yield more precise control of the induced electric field. If desirable, ECT can be made as focal as MST while using simpler stimulation equipment. Next, we demonstrate how the electric field induced by transcranial magnetic stimulation (TMS) can be controlled. We present the most comprehensive comparison of TMS coil electric field penetration and focality to date. The electric field distributions of more than 50 TMS coils were simulated. We show that TMS coils differ markedly in their electric field characteristics, but they all are subject to a consistent depth-focality tradeoff. Specifically, the ability to directly stimulate deeper brain structures is obtained at the expense of inducing wider electric field spread. Figure-8 type coils are fundamentally more focal compared to circular type coils. Understanding the depth-focality tradeoff can help researchers and clinicians to appropriately select coils and interpret TMS studies. This work also enables the development of novel TMS coils with electronically switchable active and sham modes as well as for deep TMS. Design considerations of these coils are extensively discussed. Part II of the dissertation aims to quantify the effect of individual, sex, and age differences in head geometry and conductivity on the induced neural stimulation strength and focality of ECT and MST. Across and within ECT studies, there is marked unexplained variability in seizure threshold and clinical outcomes. It is not known to what extent the age and sex effects on seizure threshold are mediated by interindividual variation in neural excitability and/or anatomy of the head. Addressing this question, we examine the effect on ECT and MST induced field characteristics of the variability in head diameter, scalp and skull thicknesses and conductivities, as well as brain volume, in a range of values that are representative of the patient population. Variations in the local tissue properties such as scalp and skull thickness and conductivity affect the existing ECT configurations more than MST. On the other hand, the existing MST coil configurations show greater sensitivity to head diameter variation compared to ECT. Due to the high focality of MST compared to ECT, the stimulated brain volume in MST is more sensitive to variation in tissue layer thicknesses. We further demonstrate how individualization of the stimulus pulse current amplitude, which is not presently done in ECT or MST, can be used as a means of compensating for interindividual anatomical variability, which could lead to better and more consistent clinical outcomes. Part III of the dissertation aims to systemically investigate, both computationally and experimentally, the safety of TMS and ECT in patients with a deep-brain stimulation system, and propose safety guidelines for the dual-device therapy. We showed that the induction of significant voltages in the subcutaneous leads in the scalp during TMS could result in unintended and potentially dangerous levels of electrical currents in the DBS electrode contacts. When applying ECT in patients with intracranial implants, we showed that there is an increase in the electric field strength in the brain due to conduction through the burr holes, especially when the burr holes are not fitted with nonconductive caps. Safety concerns presently limit the access of patients with intracranial electronic devices to therapies involving transcranial stimulation technology, which may preclude them from obtaining appropriate medical treatments. Gaining better understanding of the interactions between transcranial and implanted stimulation devices will demarcate significant safety risks from benign interactions, and will provide recommendations for reducing risk, thus enhancing the patient's therapeutic options.

In-Vivo Characterization of Glassy Carbon Micro-Electrode Arrays for Neural Applications and Histological Analysis of the Brain Tissue

NASA Astrophysics Data System (ADS)

Vomero, Maria

The aim of this work is to fabricate and characterize glassy carbon Microelectrode Arrays (MEAs) for sensing and stimulating neural activity, and conduct histological analysis of the brain tissue after the implant to determine long-term performance. Neural applications often require robust electrical and electrochemical response over a long period of time, and for those applications we propose to replace the commonly used noble metals like platinum, gold and iridium with glassy carbon. We submit that such material has the potential to improve the performances of traditional neural prostheses, thanks to better charge transfer capabilities and higher electrochemical stability. Great interest and attention is given in this work, in particular, to the investigation of tissue response after several weeks of implants in rodents' brain motor cortex and the associated materials degradation. As part of this work, a new set of devices for Electrocorticography (ECoG) has been designed and fabricated to improve durability and quality of the previous generation of devices, designed and manufactured by the same research group in 2014. In-vivo long-term impedance measurements and brain activity recordings were performed to test the functionality of the neural devices. In-vitro electrical characterization of the carbon electrodes, as well as the study of the adhesion mechanisms between glassy carbon and different substrates is also part of the research described in this book.

Control of a visual keyboard using an electrocorticographic brain-computer interface.

PubMed

Krusienski, Dean J; Shih, Jerry J

2011-05-01

Brain-computer interfaces (BCIs) are devices that enable severely disabled people to communicate and interact with their environments using their brain waves. Most studies investigating BCI in humans have used scalp EEG as the source of electrical signals and focused on motor control of prostheses or computer cursors on a screen. The authors hypothesize that the use of brain signals obtained directly from the cortical surface will more effectively control a communication/spelling task compared to scalp EEG. A total of 6 patients with medically intractable epilepsy were tested for the ability to control a visual keyboard using electrocorticographic (ECOG) signals. ECOG data collected during a P300 visual task paradigm were preprocessed and used to train a linear classifier to subsequently predict the intended target letters. The classifier was able to predict the intended target character at or near 100% accuracy using fewer than 15 stimulation sequences in 5 of the 6 people tested. ECOG data from electrodes outside the language cortex contributed to the classifier and enabled participants to write words on a visual keyboard. This is a novel finding because previous invasive BCI research in humans used signals exclusively from the motor cortex to control a computer cursor or prosthetic device. These results demonstrate that ECOG signals from electrodes both overlying and outside the language cortex can reliably control a visual keyboard to generate language output without voice or limb movements.

Deep Brain Stimulation Frequency—A Divining Rod for New and Novel Concepts of Nervous System Function and Therapy

PubMed Central

Montgomery, Erwin B.; He, Huang

2016-01-01

The efficacy of Deep Brain Stimulation (DBS) for an expanding array of neurological and psychiatric disorders demonstrates directly that DBS affects the basic electroneurophysiological mechanisms of the brain. The increasing array of active electrode configurations, stimulation currents, pulse widths, frequencies, and pulse patterns provides valuable tools to probe electroneurophysiological mechanisms. The extension of basic electroneurophysiological and anatomical concepts using sophisticated computational modeling and simulation has provided relatively straightforward explanations of all the DBS parameters except frequency. This article summarizes current thought about frequency and relevant observations. Current methodological and conceptual errors are critically examined in the hope that future work will not replicate these errors. One possible alternative theory is presented to provide a contrast to many current theories. DBS, conceptually, is a noisy discrete oscillator interacting with the basal ganglia–thalamic–cortical system of multiple re-entrant, discrete oscillators. Implications for positive and negative resonance, stochastic resonance and coherence, noisy synchronization, and holographic memory (related to movement generation) are presented. The time course of DBS neuronal responses demonstrates evolution of the DBS response consistent with the dynamics of re-entrant mechanisms. Finally, computational modeling demonstrates identical dynamics as seen by neuronal activities recorded from human and nonhuman primates, illustrating the differences of discrete from continuous harmonic oscillators and the power of conceptualizing the nervous system as composed on interacting discrete nonlinear oscillators. PMID:27548234

A conformal, bio-interfaced class of silicon electronics for mapping cardiac electrophysiology.

PubMed

Viventi, Jonathan; Kim, Dae-Hyeong; Moss, Joshua D; Kim, Yun-Soung; Blanco, Justin A; Annetta, Nicholas; Hicks, Andrew; Xiao, Jianliang; Huang, Younggang; Callans, David J; Rogers, John A; Litt, Brian

2010-03-24

In all current implantable medical devices such as pacemakers, deep brain stimulators, and epilepsy treatment devices, each electrode is independently connected to separate control systems. The ability of these devices to sample and stimulate tissues is hindered by this configuration and by the rigid, planar nature of the electronics and the electrode-tissue interfaces. Here, we report the development of a class of mechanically flexible silicon electronics for multiplexed measurement of signals in an intimate, conformal integrated mode on the dynamic, three-dimensional surfaces of soft tissues in the human body. We demonstrate this technology in sensor systems composed of 2016 silicon nanomembrane transistors configured to record electrical activity directly from the curved, wet surface of a beating porcine heart in vivo. The devices sample with simultaneous submillimeter and submillisecond resolution through 288 amplified and multiplexed channels. We use this system to map the spread of spontaneous and paced ventricular depolarization in real time, at high resolution, on the epicardial surface in a porcine animal model. This demonstration is one example of many possible uses of this technology in minimally invasive medical devices.

Direct Exploration of the Role of the Ventral Anterior Temporal Lobe in Semantic Memory: Cortical Stimulation and Local Field Potential Evidence From Subdural Grid Electrodes

PubMed Central

Shimotake, Akihiro; Matsumoto, Riki; Ueno, Taiji; Kunieda, Takeharu; Saito, Satoru; Hoffman, Paul; Kikuchi, Takayuki; Fukuyama, Hidenao; Miyamoto, Susumu; Takahashi, Ryosuke; Ikeda, Akio; Lambon Ralph, Matthew A.

2015-01-01

Semantic memory is a crucial higher cortical function that codes the meaning of objects and words, and when impaired after neurological damage, patients are left with significant disability. Investigations of semantic dementia have implicated the anterior temporal lobe (ATL) region, in general, as crucial for multimodal semantic memory. The potentially crucial role of the ventral ATL subregion has been emphasized by recent functional neuroimaging studies, but the necessity of this precise area has not been selectively tested. The implantation of subdural electrode grids over this subregion, for the presurgical assessment of patients with partial epilepsy or brain tumor, offers the dual yet rare opportunities to record cortical local field potentials while participants complete semantic tasks and to stimulate the functionally identified regions in the same participants to evaluate the necessity of these areas in semantic processing. Across 6 patients, and utilizing a variety of semantic assessments, we evaluated and confirmed that the anterior fusiform/inferior temporal gyrus is crucial in multimodal, receptive, and expressive, semantic processing. PMID:25491206

Rhythmic entrainment source separation: Optimizing analyses of neural responses to rhythmic sensory stimulation.

PubMed

Cohen, Michael X; Gulbinaite, Rasa

2017-02-15

Steady-state evoked potentials (SSEPs) are rhythmic brain responses to rhythmic sensory stimulation, and are often used to study perceptual and attentional processes. We present a data analysis method for maximizing the signal-to-noise ratio of the narrow-band steady-state response in the frequency and time-frequency domains. The method, termed rhythmic entrainment source separation (RESS), is based on denoising source separation approaches that take advantage of the simultaneous but differential projection of neural activity to multiple electrodes or sensors. Our approach is a combination and extension of existing multivariate source separation methods. We demonstrate that RESS performs well on both simulated and empirical data, and outperforms conventional SSEP analysis methods based on selecting electrodes with the strongest SSEP response, as well as several other linear spatial filters. We also discuss the potential confound of overfitting, whereby the filter captures noise in absence of a signal. Matlab scripts are available to replicate and extend our simulations and methods. We conclude with some practical advice for optimizing SSEP data analyses and interpreting the results. Copyright © 2016 Elsevier Inc. All rights reserved.

Feasibility of recording high frequency oscillations with tripolar concentric ring electrodes during pentylenetetrazole-induced seizures in rats.

PubMed

Makeyev, Oleksandr; Liu, Xiang; Wang, Liling; Zhu, Zhenghan; Taveras, Aristides; Troiano, Derek; Medvedev, Andrei V; Besio, Walter G

2012-01-01

As epilepsy remains a refractory condition in about 30% of patients with complex partial seizures, electrical stimulation of the brain has recently shown potential for additive seizure control therapy. Previously, we applied noninvasive transcranial focal stimulation via novel tripolar concentric ring electrodes (TCREs) on the scalp of rats after inducing seizures with pentylenetetrazole (PTZ). We developed a close-loop system to detect seizures and automatically trigger the stimulation and evaluated its effect on the electrographic activity recorded by TCREs in rats. In our previous work the detectors of seizure onset were based on seizure-induced changes in signal power in the frequency range up to 100 Hz, while in this preliminary study we assess the feasibility of recording high frequency oscillations (HFOs) in the range up to 300 Hz noninvasively with scalp TCREs during PTZ-induced seizures. Grand average power spectral density estimate and generalized likelihood ratio tests were used to compare power of electrographic activity at different stages of seizure development in a group of rats (n= 8). The results suggest that TCREs have the ability to record HFOs from the scalp as well as that scalp-recorded HFOs can potentially be used as features for seizure onset detection.

Conformable actively multiplexed high-density surface electrode array for brain interfacing

DOEpatents

Rogers, John; Kim, Dae-Hyeong; Litt, Brian; Viventi, Jonathan

2015-01-13

Provided are methods and devices for interfacing with brain tissue, specifically for monitoring and/or actuation of spatio-temporal electrical waveforms. The device is conformable having a high electrode density and high spatial and temporal resolution. A conformable substrate supports a conformable electronic circuit and a barrier layer. Electrodes are positioned to provide electrical contact with a brain tissue. A controller monitors or actuates the electrodes, thereby interfacing with the brain tissue. In an aspect, methods are provided to monitor or actuate spatio-temporal electrical waveform over large brain surface areas by any of the devices disclosed herein.

Portable wireless electrocorticography system with a flexible microelectrodes array for epilepsy treatment.

PubMed

Xie, Kejun; Zhang, Shaomin; Dong, Shurong; Li, Shijian; Yu, Chaonan; Xu, Kedi; Chen, Wanke; Guo, Wei; Luo, Jikui; Wu, Zhaohui

2017-08-10

In this paper, we present a portable wireless electrocorticography (ECoG) system. It uses a high resolution 32-channel flexible ECoG electrodes array to collect electrical signals of brain activities and to stimulate the lesions. Electronic circuits are designed for signal acquisition, processing and transmission using Bluetooth Low Energy 4 (LTE4) for wireless communication with cell phone. In-vivo experiments on a rat show that the flexible ECoG system can accurately record electrical signals of brain activities and transmit them to cell phone with a maximal sampling rate of 30 ksampling/s per channel. It demonstrates that the epilepsy lesions can be detected, located and treated through the ECoG system. The wireless ECoG system has low energy consumption and high brain spatial resolution, thus has great prospects for future application.

Intrasulcal Electrocorticography in Macaque Monkeys with Minimally Invasive Neurosurgical Protocols

PubMed Central

Matsuo, Takeshi; Kawasaki, Keisuke; Osada, Takahiro; Sawahata, Hirohito; Suzuki, Takafumi; Shibata, Masahiro; Miyakawa, Naohisa; Nakahara, Kiyoshi; Iijima, Atsuhiko; Sato, Noboru; Kawai, Kensuke; Saito, Nobuhito; Hasegawa, Isao

2011-01-01

Electrocorticography (ECoG), multichannel brain-surface recording and stimulation with probe electrode arrays, has become a potent methodology not only for clinical neurosurgery but also for basic neuroscience using animal models. The highly evolved primate's brain has deep cerebral sulci, and both gyral and intrasulcal cortical regions have been implicated in important functional processes. However, direct experimental access is typically limited to gyral regions, since placing probes into sulci is difficult without damaging the surrounding tissues. Here we describe a novel methodology for intrasulcal ECoG in macaque monkeys. We designed and fabricated ultra-thin flexible probes for macaques with micro-electro-mechanical systems technology. We developed minimally invasive operative protocols to implant the probes by introducing cutting-edge devices for human neurosurgery. To evaluate the feasibility of intrasulcal ECoG, we conducted electrophysiological recording and stimulation experiments. First, we inserted parts of the Parylene-C-based probe into the superior temporal sulcus to compare visually evoked ECoG responses from the ventral bank of the sulcus with those from the surface of the inferior temporal cortex. Analyses of power spectral density and signal-to-noise ratio revealed that the quality of the ECoG signal was comparable inside and outside of the sulcus. Histological examination revealed no obvious physical damage in the implanted areas. Second, we placed a modified silicone ECoG probe into the central sulcus and also on the surface of the precentral gyrus for stimulation. Thresholds for muscle twitching were significantly lower during intrasulcal stimulation compared to gyral stimulation. These results demonstrate the feasibility of intrasulcal ECoG in macaques. The novel methodology proposed here opens up a new frontier in neuroscience research, enabling the direct measurement and manipulation of electrical activity in the whole brain. PMID:21647392

Cortico-cortical and motor evoked potentials to single and paired-pulse stimuli: An exploratory transcranial magnetic and intracranial electric brain stimulation study.

PubMed

Boulogne, Sébastien; Andre-Obadia, Nathalie; Kimiskidis, Vasilios K; Ryvlin, Philippe; Rheims, Sylvain

2016-11-01

Paired-pulse (PP) paradigms are commonly employed to assess in vivo cortical excitability using transcranial magnetic stimulation (TMS) to stimulate the primary motor cortex and modulate the induced motor evoked potential (MEP). Single-pulse cortical direct electrical stimulation (DES) during intracerebral EEG monitoring allows the investigation of brain connectivity by eliciting cortico-cortical evoked potentials (CCEPs). However, PP paradigm using intracerebral DES has rarely been reported and has never been previously compared with TMS. The work was intended (i) to verify that the well-established modulations of MEPs following PP TMS remain similar using DES in the motor cortex, and (ii) to evaluate if a similar pattern could be observed in distant cortico-cortical connections through modulations of CCEP. Three patients undergoing intracerebral EEG monitoring with electrodes implanted in the central region were studied. Single-pulse DES (1-3 mA, 1 ms, 0.2 Hz) and PP DES using six interstimulus intervals (5, 15, 30, 50, 100, and 200 ms) in the motor cortex with concomitant recording of CCEPs and MEPs in contralateral muscles were performed. Finally, a navigated PP TMS session targeted the intracranial stimulation site to record TMS-induced MEPs in two patients. MEP modulations elicited by PP intracerebral DES proved similar among the three patients and to those obtained by PP TMS. CCEP modulations elicited by PP intracerebral DES usually showed a pattern comparable to that of MEP, although a different pattern could be observed occasionally. PP intracerebral DES seems to involve excitatory and inhibitory mechanisms similar to PP TMS and allows the recording of intracortical inhibition and facilitation modulation on cortico-cortical connections. Hum Brain Mapp 37:3767-3778, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Long-term enhancement of synaptic transmission between antennal lobe and mushroom body in cultured Drosophila brain.

PubMed

Ueno, Kohei; Naganos, Shintaro; Hirano, Yukinori; Horiuchi, Junjiro; Saitoe, Minoru

2013-01-01

In Drosophila, the mushroom body (MB) is a critical brain structure for olfactory associative learning. During aversive conditioning, the MBs are thought to associate odour signals, conveyed by projection neurons (PNs) from the antennal lobe (AL), with shock signals conveyed through ascending fibres of the ventral nerve cord (AFV). Although synaptic transmission between AL and MB might play a crucial role for olfactory associative learning, its physiological properties have not been examined directly. Using a cultured Drosophila brain expressing a Ca(2+) indicator in the MBs, we investigated synaptic transmission and plasticity at the AL-MB synapse. Following stimulation with a glass micro-electrode, AL-induced Ca(2+) responses in the MBs were mediated through Drosophila nicotinic acetylcholine receptors (dnAChRs), while AFV-induced Ca(2+) responses were mediated through Drosophila NMDA receptors (dNRs). AL-MB synaptic transmission was enhanced more than 2 h after the simultaneous 'associative-stimulation' of AL and AFV, and such long-term enhancement (LTE) was specifically formed at the AL-MB synapses but not at the AFV-MB synapses. AL-MB LTE was not induced by intense stimulation of the AL alone, and the LTE decays within 60 min after subsequent repetitive AL stimulation. These phenotypes of associativity, input specificity and persistence of AL-MB LTE are highly reminiscent of olfactory memory. Furthermore, similar to olfactory aversive memory, AL-MB LTE formation required activation of the Drosophila D1 dopamine receptor, DopR, along with dnAChR and dNR during associative stimulations. These physiological and genetic analogies indicate that AL-MB LTE might be a relevant cellular model for olfactory memory.

Modulation of motor performance and motor learning by transcranial direct current stimulation.

PubMed

Reis, Janine; Fritsch, Brita

2011-12-01

Transcranial direct current stimulation (tDCS) has shown preliminary success in improving motor performance and motor learning in healthy individuals, and restitution of motor deficits in stroke patients. This brief review highlights some recent work. Within the past years, behavioural studies have confirmed and specified the timing and polarity specific effects of tDCS on motor skill learning and motor adaptation. There is strong evidence that timely co-application of (hand/arm) training and anodal tDCS to the contralateral M1 can improve motor learning. Improvements in motor function as measured by clinical scores have been described for combined tDCS and training in stroke patients. For this purpose, electrode montages have been modified with respect to interhemispheric imbalance after brain injury. Cathodal tDCS applied to the unlesioned M1 or bihemispheric M1 stimulation appears to be well tolerated and useful to induce improvements in motor function. Mechanistic studies in humans and animals are discussed with regard to physiological motor learning. tDCS is well tolerated, easy to use and capable of inducing lasting improvements in motor function. This method holds promise for the rehabilitation of motor disabilities, although acute studies in patients with brain injury are so far lacking.

The phenomenology of deep brain stimulation-induced changes in OCD: an enactive affordance-based model

PubMed Central

de Haan, Sanneke; Rietveld, Erik; Stokhof, Martin; Denys, Damiaan

2013-01-01

People suffering from Obsessive-Compulsive Disorder (OCD) do things they do not want to do, and/or they think things they do not want to think. In about 10% of OCD patients, none of the available treatment options is effective. A small group of these patients is currently being treated with deep brain stimulation (DBS). DBS involves the implantation of electrodes in the brain. These electrodes give a continuous electrical pulse to the brain area in which they are implanted. It turns out that patients may experience profound changes as a result of DBS treatment. It is not just the symptoms that change; patients rather seem to experience a different way of being in the world. These global effects are insufficiently captured by traditional psychiatric scales, which mainly consist of behavioral measures of the severity of the symptoms. In this article we aim to capture the changes in the patients' phenomenology and make sense of the broad range of changes they report. For that we introduce an enactive, affordance-based model that fleshes out the dynamic interactions between person and world in four aspects. The first aspect is the patients' experience of the world. We propose to specify the patients' world in terms of a field of affordances, with the three dimensions of broadness of scope (“width” of the field), temporal horizon (“depth”), and relevance of the perceived affordances (“height”). The second aspect is the person-side of the interaction, that is, the patients' self-experience, notably their moods and feelings. Thirdly, we point to the different characteristics of the way in which patients relate to the world. And lastly, the existential stance refers to the stance that patients take toward the changes they experience: the second-order evaluative relation to their interactions and themselves. With our model we intend to specify the notion of being in the world in order to do justice to the phenomenological effects of DBS treatment. PMID:24133438

Action potentials in retinal ganglion cells are initiated at the site of maximal curvature of the extracellular potential.

PubMed

Eickenscheidt, Max; Zeck, Günther

2014-06-01

The initiation of an action potential by extracellular stimulation occurs after local depolarization of the neuronal membrane above threshold. Although the technique shows remarkable clinical success, the site of action and the relevant stimulation parameters are not completely understood. Here we identify the site of action potential initiation in rabbit retinal ganglion cells (RGCs) interfaced to an array of extracellular capacitive stimulation electrodes. We determine which feature of the extracellular potential governs action potential initiation by simultaneous stimulation and recording RGCs interfaced in epiretinal configuration. Stimulation electrodes were combined to areas of different size and were presented at different positions with respect to the RGC. Based on stimulation by electrodes beneath the RGC soma and simultaneous sub-millisecond latency measurement we infer axonal initiation at the site of maximal curvature of the extracellular potential. Stimulation by electrodes at different positions along the axon reveals a nearly constant threshold current density except for a narrow region close to the cell soma. These findings are explained by the concept of the activating function modified to consider a region of lower excitability close to the cell soma. We present a framework how to estimate the site of action potential initiation and the stimulus required to cross threshold in neurons tightly interfaced to capacitive stimulation electrodes. Our results underscore the necessity of rigorous electrical characterization of the stimulation electrodes and of the interfaced neural tissue.

Electrical receptive fields of retinal ganglion cells: Influence of presynaptic neurons

PubMed Central

Apollo, Nicholas V.; Garrett, David J.

2018-01-01

Implantable retinal stimulators activate surviving neurons to restore a sense of vision in people who have lost their photoreceptors through degenerative diseases. Complex spatial and temporal interactions occur in the retina during multi-electrode stimulation. Due to these complexities, most existing implants activate only a few electrodes at a time, limiting the repertoire of available stimulation patterns. Measuring the spatiotemporal interactions between electrodes and retinal cells, and incorporating them into a model may lead to improved stimulation algorithms that exploit the interactions. Here, we present a computational model that accurately predicts both the spatial and temporal nonlinear interactions of multi-electrode stimulation of rat retinal ganglion cells (RGCs). The model was verified using in vitro recordings of ON, OFF, and ON-OFF RGCs in response to subretinal multi-electrode stimulation with biphasic pulses at three stimulation frequencies (10, 20, 30 Hz). The model gives an estimate of each cell’s spatiotemporal electrical receptive fields (ERFs); i.e., the pattern of stimulation leading to excitation or suppression in the neuron. All cells had excitatory ERFs and many also had suppressive sub-regions of their ERFs. We show that the nonlinearities in observed responses arise largely from activation of presynaptic interneurons. When synaptic transmission was blocked, the number of sub-regions of the ERF was reduced, usually to a single excitatory ERF. This suggests that direct cell activation can be modeled accurately by a one-dimensional model with linear interactions between electrodes, whereas indirect stimulation due to summated presynaptic responses is nonlinear. PMID:29432411

Multichannel activity propagation across an engineered axon network

NASA Astrophysics Data System (ADS)

Chen, H. Isaac; Wolf, John A.; Smith, Douglas H.

2017-04-01

Objective. Although substantial progress has been made in mapping the connections of the brain, less is known about how this organization translates into brain function. In particular, the massive interconnectivity of the brain has made it difficult to specifically examine data transmission between two nodes of the connectome, a central component of the ‘neural code.’ Here, we investigated the propagation of multiple streams of asynchronous neuronal activity across an isolated in vitro ‘connectome unit.’ Approach. We used the novel technique of axon stretch growth to create a model of a long-range cortico-cortical network, a modular system consisting of paired nodes of cortical neurons connected by axon tracts. Using optical stimulation and multi-electrode array recording techniques, we explored how input patterns are represented by cortical networks, how these representations shift as they are transmitted between cortical nodes and perturbed by external conditions, and how well the downstream node distinguishes different patterns. Main results. Stimulus representations included direct, synaptic, and multiplexed responses that grew in complexity as the distance between the stimulation source and recorded neuron increased. These representations collapsed into patterns with lower information content at higher stimulation frequencies. With internodal activity propagation, a hierarchy of network pathways, including latent circuits, was revealed using glutamatergic blockade. As stimulus channels were added, divergent, non-linear effects were observed in local versus distant network layers. Pairwise difference analysis of neuronal responses suggested that neuronal ensembles generally outperformed individual cells in discriminating input patterns. Significance. Our data illuminate the complexity of spiking activity propagation in cortical networks in vitro, which is characterized by the transformation of an input into myriad outputs over several network layers. These results provide insight into how the brain potentially processes information and generates the neural code and could guide the development of clinical therapies based on multichannel brain stimulation.

A novel neural prosthesis providing long-term electrocorticography recording and cortical stimulation for epilepsy and brain-computer interface.

PubMed

Romanelli, Pantaleo; Piangerelli, Marco; Ratel, David; Gaude, Christophe; Costecalde, Thomas; Puttilli, Cosimo; Picciafuoco, Mauro; Benabid, Alim; Torres, Napoleon

2018-05-11

OBJECTIVE Wireless technology is a novel tool for the transmission of cortical signals. Wireless electrocorticography (ECoG) aims to improve the safety and diagnostic gain of procedures requiring invasive localization of seizure foci and also to provide long-term recording of brain activity for brain-computer interfaces (BCIs). However, no wireless devices aimed at these clinical applications are currently available. The authors present the application of a fully implantable and externally rechargeable neural prosthesis providing wireless ECoG recording and direct cortical stimulation (DCS). Prolonged wireless ECoG monitoring was tested in nonhuman primates by using a custom-made device (the ECoG implantable wireless 16-electrode [ECOGIW-16E] device) containing a 16-contact subdural grid. This is a preliminary step toward large-scale, long-term wireless ECoG recording in humans. METHODS The authors implanted the ECOGIW-16E device over the left sensorimotor cortex of a nonhuman primate ( Macaca fascicularis), recording ECoG signals over a time span of 6 months. Daily electrode impedances were measured, aiming to maintain the impedance values below a threshold of 100 KΩ. Brain mapping was obtained through wireless cortical stimulation at fixed intervals (1, 3, and 6 months). After 6 months, the device was removed. The authors analyzed cortical tissues by using conventional histological and immunohistological investigation to assess whether there was evidence of damage after the long-term implantation of the grid. RESULTS The implant was well tolerated; no neurological or behavioral consequences were reported in the monkey, which resumed his normal activities within a few hours of the procedure. The signal quality of wireless ECoG remained excellent over the 6-month observation period. Impedance values remained well below the threshold value; the average impedance per contact remains approximately 40 KΩ. Wireless cortical stimulation induced movements of the upper and lower limbs, and elicited fine movements of the digits as well. After the monkey was euthanized, the grid was found to be encapsulated by a newly formed dural sheet. The grid removal was performed easily, and no direct adhesions of the grid to the cortex were found. Conventional histological studies showed no cortical damage in the brain region covered by the grid, except for a single microscopic spot of cortical necrosis (not visible to the naked eye) in a region that had undergone repeated procedures of electrical stimulation. Immunohistological studies of the cortex underlying the grid showed a mild inflammatory process. CONCLUSIONS This preliminary experience in a nonhuman primate shows that a wireless neuroprosthesis, with related long-term ECoG recording (up to 6 months) and multiple DCSs, was tolerated without sequelae. The authors predict that epilepsy surgery could realize great benefit from this novel prosthesis, providing an extended time span for ECoG recording.

Inter-electrode tissue resistance is not affected by tissue oedema when electrically stimulating the lower limb of sepsis patients.

PubMed

Durfee, William K; Young, Joseph R; Ginz, Hans F

2014-05-01

ICU patients typically are given large amounts of fluid and often develop oedema. The purpose of this study was to evaluate whether the oedema would change inter-electrode resistance and, thus, require a different approach to using non-invasive electrical stimulation of nerves to assess muscle force. Inter-electrode tissue resistance in the lower leg was measured by applying a 300 µs constant current pulse and measuring the current through and voltage across the stimulating electrodes. The protocol was administered to nine ICU patients with oedema, eight surgical patients without oedema and eight healthy controls. No significant difference in inter-electrode resistance was found between the three groups. For all groups, resistance decreased as stimulation current increased. In conclusion, inter-electrode resistance in ICU patients with severe oedema is the same as the resistance in regular surgical patients and healthy controls. This means that non-invasive nerve stimulation devices do not need to be designed to accommodate different resistances when used with oedema patients; however, surface stimulation does require higher current levels with oedema patients because of the increased distance between the skin surface and the targeted nerve or muscle.

Electrochemical properties of titanium nitride nerve stimulation electrodes: an in vitro and in vivo study

PubMed Central

Meijs, Suzan; Fjorback, Morten; Jensen, Carina; Sørensen, Søren; Rechendorff, Kristian; Rijkhoff, Nico J. M.

2015-01-01

The in vivo electrochemical behavior of titanium nitride (TiN) nerve stimulation electrodes was compared to their in vitro behavior for a period of 90 days. Ten electrodes were implanted in two Göttingen minipigs. Four of these were used for electrical stimulation and electrochemical measurements. Five electrodes were kept in Ringer's solution at 37.5°C, of which four were used for electrical stimulation and electrochemical measurements. The voltage transients measured in vivo were 13 times greater than in vitro at implantation and they continued to increase with time. The electrochemical properties in vivo and the tissue resistance (Rtissue) followed a similar trend with time. There was no consistent significant difference between the electrochemical properties of the in vivo and in vitro electrodes after the implanted period. The differences between the in vivo and in vitro electrodes during the implanted period show that the evaluation of electrochemical performance of implantable stimulation electrodes cannot be substituted with in vitro measurements. After the implanted period, however, the performance of the in vivo and in vitro electrodes in saline was similar. In addition, the changes observed over time during the post-implantation period regarding the electrochemical properties of the in vivo electrodes and Rtissue were similar, which indicates that these changes are due to the foreign body response to implantation. PMID:26300717

Implantation of a 16-channel functional electrical stimulation walking system.

PubMed

Sharma, M; Marsolais, E B; Polando, G; Triolo, R J; Davis, J A; Bhadra, N; Uhlir, J P

1998-02-01

A 16-channel electrical stimulation system was implanted in a 39-year-old patient with T10 paraplegia to restore sit to stand, walking, and exercise functions. System implantation required two surgical sessions. In the first session, the posterior muscle set consisting of bilateral semimembranosus, adductor magnus, and gluteus maximus muscles were exposed and epimysial electrodes sutured at the point of greatest muscle contraction. Closed double helix intramuscular electrodes were implanted in the erector spinae. Two weeks later, epimysial electrodes were attached to the eight anterior muscles consisting of the tibialis anterior, sartorius, tensor fasciae latae, and vastus lateralis with all 16 electrode leads passed to the anterior abdominal wall. The electrodes were connected to two eight-channel stimulators placed in the iliac fossae, and the system was checked by activating the individual muscles. The implanted stimulators received stimulation instructions and power via a radio frequency link to an external control. Stimulation patterns for standing, walking, sitting, and exercise functions were chosen from a preprogrammed menu via a finger key pad. After 3 weeks of restricted patient activity, all electrodes stimulated either the target muscle or had an acceptable spillover pattern. The patient is undergoing a 16-week rehabilitation course of stimulated exercises gradually increasing in intensity. At the conclusion, the goal is to discharge the patient with the system for spontaneous use. Although long term followup is required to determine system reliability, preliminary clinical results indicate that targeted, repeatable, functional muscle contractions in the lower extremity can be achieved with a system consisting of epimysial electrodes.

Increased dopamine receptor expression and anti-depressant response following deep brain stimulation of the medial forebrain bundle.

PubMed

Dandekar, Manoj P; Luse, Dustin; Hoffmann, Carson; Cotton, Patrick; Peery, Travis; Ruiz, Christian; Hussey, Caroline; Giridharan, Vijayasree V; Soares, Jair C; Quevedo, Joao; Fenoy, Albert J

2017-08-01

Among several potential neuroanatomical targets pursued for deep brain stimulation (DBS) for treating those with treatment-resistant depression (TRD), the superolateral-branch of the medial forebrain bundle (MFB) is emerging as a privileged location. We investigated the antidepressant-like phenotypic and chemical changes associated with reward-processing dopaminergic systems in rat brains after MFB-DBS. Male Wistar rats were divided into three groups: sham-operated, DBS-Off, and DBS-On. For DBS, a concentric bipolar electrode was stereotactically implanted into the right MFB. Exploratory activity and depression-like behavior were evaluated using the open-field and forced-swimming test (FST), respectively. MFB-DBS effects on the dopaminergic system were evaluated using immunoblotting for tyrosine hydroxylase (TH), dopamine transporter (DAT), and dopamine receptors (D1-D5), and high-performance liquid chromatography for quantifying dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in brain homogenates of prefrontal cortex (PFC), hippocampus, amygdala, and nucleus accumbens (NAc). Animals receiving MFB-DBS showed a significant increase in swimming time without alterations in locomotor activity, relative to the DBS-Off (p<0.039) and sham-operated groups (p<0.014), indicating an antidepressant-like response. MFB-DBS led to a striking increase in protein levels of dopamine D2 receptors and DAT in the PFC and hippocampus, respectively. However, we did not observe appreciable differences in the expression of other dopamine receptors, TH, or in the concentrations of dopamine, DOPAC, and HVA in PFC, hippocampus, amygdala, and NAc. This study was not performed on an animal model of TRD. MFB-DBS rescues the depression-like phenotypes and selectively activates expression of dopamine receptors in brain regions distant from the target area of stimulation. Copyright © 2017. Published by Elsevier B.V.

In vitro assessment of tissue heating near metallic medical implants by exposure to pulsed radio frequency diathermy

NASA Astrophysics Data System (ADS)

Ruggera, P. S.; Witters, D. M.; von Maltzahn, G.; Bassen, H. I.

2003-09-01

A patient with bilateral implanted neurostimulators suffered significant brain tissue damage, and subsequently died, following diathermy treatment to hasten recovery from teeth extraction. Subsequent MRI examinations showed acute deterioration of the tissue near the deep brain stimulator (DBS) lead's electrodes which was attributed to excessive tissue heating induced by the diathermy treatment. Though not published in the open literature, a second incident was reported for a patient with implanted neurostimulators for the treatment of Parkinson's disease. During a diathermy treatment for severe kyphosis, the patient had a sudden change in mental status and neurological deficits. The diathermy was implicated in causing damage to the patient's brain tissue. To investigate if diathermy induced excessive heating was possible with other types of implantable lead systems, or metallic implants in general, we conducted a series of in vitro laboratory tests. We obtained a diathermy unit and also assembled a controllable laboratory exposure system. Specific absorption rate (SAR) measurements were performed using fibre optic thermometry in proximity to the implants to determine the rate of temperature rise using typical diathermy treatment power levels. Comparisons were made of the SAR measurements for a spinal cord stimulator (SCS) lead, a pacemaker lead and three types of bone prosthesis (screws, rods and a plate). Findings indicate that temperature changes of 2.54 and 4.88 °C s-1 with corresponding SAR values of 9129 and 17 563 W kg-1 near the SCS and pacemaker electrodes are significantly higher than those found in the proximity of the other metallic implants which ranged from 0.04 to 0.69 °C s-1 (129 to 2471 W kg-1). Since the DBS leads that were implanted in the reported human incidents have one-half the electrode surface area of the tested SCS lead, these results imply that tissue heating at rates at least equal to or up to twice as much as those reported here for the SCS lead could occur for the DBS leads.

Evolving Applications, Technological Challenges and Future Opportunities in Neuromodulation: Proceedings of the Fifth Annual Deep Brain Stimulation Think Tank

PubMed Central

Ramirez-Zamora, Adolfo; Giordano, James J.; Gunduz, Aysegul; Brown, Peter; Sanchez, Justin C.; Foote, Kelly D.; Almeida, Leonardo; Starr, Philip A.; Bronte-Stewart, Helen M.; Hu, Wei; McIntyre, Cameron; Goodman, Wayne; Kumsa, Doe; Grill, Warren M.; Walker, Harrison C.; Johnson, Matthew D.; Vitek, Jerrold L.; Greene, David; Rizzuto, Daniel S.; Song, Dong; Berger, Theodore W.; Hampson, Robert E.; Deadwyler, Sam A.; Hochberg, Leigh R.; Schiff, Nicholas D.; Stypulkowski, Paul; Worrell, Greg; Tiruvadi, Vineet; Mayberg, Helen S.; Jimenez-Shahed, Joohi; Nanda, Pranav; Sheth, Sameer A.; Gross, Robert E.; Lempka, Scott F.; Li, Luming; Deeb, Wissam; Okun, Michael S.

2018-01-01

The annual Deep Brain Stimulation (DBS) Think Tank provides a focal opportunity for a multidisciplinary ensemble of experts in the field of neuromodulation to discuss advancements and forthcoming opportunities and challenges in the field. The proceedings of the fifth Think Tank summarize progress in neuromodulation neurotechnology and techniques for the treatment of a range of neuropsychiatric conditions including Parkinson's disease, dystonia, essential tremor, Tourette syndrome, obsessive compulsive disorder, epilepsy and cognitive, and motor disorders. Each section of this overview of the meeting provides insight to the critical elements of discussion, current challenges, and identified future directions of scientific and technological development and application. The report addresses key issues in developing, and emphasizes major innovations that have occurred during the past year. Specifically, this year's meeting focused on technical developments in DBS, design considerations for DBS electrodes, improved sensors, neuronal signal processing, advancements in development and uses of responsive DBS (closed-loop systems), updates on National Institutes of Health and DARPA DBS programs of the BRAIN initiative, and neuroethical and policy issues arising in and from DBS research and applications in practice. PMID:29416498

Evolving Applications, Technological Challenges and Future Opportunities in Neuromodulation: Proceedings of the Fifth Annual Deep Brain Stimulation Think Tank.

PubMed

Ramirez-Zamora, Adolfo; Giordano, James J; Gunduz, Aysegul; Brown, Peter; Sanchez, Justin C; Foote, Kelly D; Almeida, Leonardo; Starr, Philip A; Bronte-Stewart, Helen M; Hu, Wei; McIntyre, Cameron; Goodman, Wayne; Kumsa, Doe; Grill, Warren M; Walker, Harrison C; Johnson, Matthew D; Vitek, Jerrold L; Greene, David; Rizzuto, Daniel S; Song, Dong; Berger, Theodore W; Hampson, Robert E; Deadwyler, Sam A; Hochberg, Leigh R; Schiff, Nicholas D; Stypulkowski, Paul; Worrell, Greg; Tiruvadi, Vineet; Mayberg, Helen S; Jimenez-Shahed, Joohi; Nanda, Pranav; Sheth, Sameer A; Gross, Robert E; Lempka, Scott F; Li, Luming; Deeb, Wissam; Okun, Michael S

2017-01-01

The annual Deep Brain Stimulation (DBS) Think Tank provides a focal opportunity for a multidisciplinary ensemble of experts in the field of neuromodulation to discuss advancements and forthcoming opportunities and challenges in the field. The proceedings of the fifth Think Tank summarize progress in neuromodulation neurotechnology and techniques for the treatment of a range of neuropsychiatric conditions including Parkinson's disease, dystonia, essential tremor, Tourette syndrome, obsessive compulsive disorder, epilepsy and cognitive, and motor disorders. Each section of this overview of the meeting provides insight to the critical elements of discussion, current challenges, and identified future directions of scientific and technological development and application. The report addresses key issues in developing, and emphasizes major innovations that have occurred during the past year. Specifically, this year's meeting focused on technical developments in DBS, design considerations for DBS electrodes, improved sensors, neuronal signal processing, advancements in development and uses of responsive DBS (closed-loop systems), updates on National Institutes of Health and DARPA DBS programs of the BRAIN initiative, and neuroethical and policy issues arising in and from DBS research and applications in practice.

Stimulation of abdominal and upper thoracic muscles with surface electrodes for respiration and cough: Acute studies in adult canines.

PubMed

Walter, James S; Posluszny, Joseph; Dieter, Raymond; Dieter, Robert S; Sayers, Scott; Iamsakul, Kiratipath; Staunton, Christine; Thomas, Donald; Rabbat, Mark; Singh, Sanjay

2018-05-01

To optimize maximal respiratory responses with surface stimulation over abdominal and upper thorax muscles and using a 12-Channel Neuroprosthetic Platform. Following instrumentation, six anesthetized adult canines were hyperventilated sufficiently to produce respiratory apnea. Six abdominal tests optimized electrode arrangements and stimulation parameters using bipolar sets of 4.5 cm square electrodes. Tests in the upper thorax optimized electrode locations, and forelimb moment was limited to slight-to-moderate. During combined muscle stimulation tests, the upper thoracic was followed immediately by abdominal stimulation. Finally, a model of glottal closure for cough was conducted with the goal of increased peak expiratory flow. Optimized stimulation of abdominal muscles included three sets of bilateral surface electrodes located 4.5 cm dorsal to the lateral line and from the 8 th intercostal space to caudal to the 13 th rib, 80 or 100 mA current, and 50 Hz stimulation frequency. The maximal expired volume was 343 ± 23 ml (n=3). Optimized upper thorax stimulation included a single bilateral set of electrodes located over the 2 nd interspace, 60 to 80 mA, and 50 Hz. The maximal inspired volume was 304 ± 54 ml (n=4). Sequential stimulation of the two muscles increased the volume to 600 ± 152 ml (n=2), and the glottal closure maneuver increased the flow. Studies in an adult canine model identified optimal surface stimulation methods for upper thorax and abdominal muscles to induce sufficient volumes for ventilation and cough. Further study with this neuroprosthetic platform is warranted.

A multi-pad electrode based functional electrical stimulation system for restoration of grasp

PubMed Central

2012-01-01

Background Functional electrical stimulation (FES) applied via transcutaneous electrodes is a common rehabilitation technique for assisting grasp in patients with central nervous system lesions. To improve the stimulation effectiveness of conventional FES, we introduce multi-pad electrodes and a new stimulation paradigm. Methods The new FES system comprises an electrode composed of small pads that can be activated individually. This electrode allows the targeting of motoneurons that activate synergistic muscles and produce a functional movement. The new stimulation paradigm allows asynchronous activation of motoneurons and provides controlled spatial distribution of the electrical charge that is delivered to the motoneurons. We developed an automated technique for the determination of the preferred electrode based on a cost function that considers the required movement of the fingers and the stabilization of the wrist joint. The data used within the cost function come from a sensorized garment that is easy to implement and does not require calibration. The design of the system also includes the possibility for fine-tuning and adaptation with a manually controllable interface. Results The device was tested on three stroke patients. The results show that the multi-pad electrodes provide the desired level of selectivity and can be used for generating a functional grasp. The results also show that the procedure, when performed on a specific user, results in the preferred electrode configuration characteristics for that patient. The findings from this study are of importance for the application of transcutaneous stimulation in the clinical and home environments. PMID:23009589

Magnetic resonance-transcranial ultrasound fusion imaging: A novel tool for brain electrode location.

PubMed

Walter, Uwe; Müller, Jan-Uwe; Rösche, Johannes; Kirsch, Michael; Grossmann, Annette; Benecke, Reiner; Wittstock, Matthias; Wolters, Alexander

2016-03-01

A combination of preoperative magnetic resonance imaging (MRI) with real-time transcranial ultrasound, known as fusion imaging, may improve postoperative control of deep brain stimulation (DBS) electrode location. Fusion imaging, however, employs a weak magnetic field for tracking the position of the ultrasound transducer and the patient's head. Here we assessed its feasibility, safety, and clinical relevance in patients with DBS. Eighteen imaging sessions were conducted in 15 patients (7 women; aged 52.4 ± 14.4 y) with DBS of subthalamic nucleus (n = 6), globus pallidus interna (n = 5), ventro-intermediate (n = 3), or anterior (n = 1) thalamic nucleus and clinically suspected lead displacement. Minimum distance between DBS generator and magnetic field transmitter was kept at 65 cm. The pre-implantation MRI dataset was loaded into the ultrasound system for the fusion imaging examination. The DBS lead position was rated using validated criteria. Generator DBS parameters and neurological state of patients were monitored. Magnetic resonance-ultrasound fusion imaging and volume navigation were feasible in all cases and provided with real-time imaging capabilities of DBS lead and its location within the superimposed magnetic resonance images. Of 35 assessed lead locations, 30 were rated optimal, three suboptimal, and two displaced. In two cases, electrodes were re-implanted after confirming their inappropriate location on computed tomography (CT) scan. No influence of fusion imaging on clinical state of patients, or on DBS implantable pulse generator function, was found. Magnetic resonance-ultrasound real-time fusion imaging of DBS electrodes is safe with distinct precautions and improves assessment of electrode location. It may lower the need for repeated CT or MRI scans in DBS patients. © 2015 International Parkinson and Movement Disorder Society.

A study of the dynamics of seizure propagation across micro domains in the vicinity of the seizure onset zone.

PubMed

Basu, Ishita; Kudela, Pawel; Korzeniewska, Anna; Franaszczuk, Piotr J; Anderson, William S

2015-08-01

The use of micro-electrode arrays to measure electrical activity from the surface of the brain is increasingly being investigated as a means to improve seizure onset zone (SOZ) localization. In this work, we used a multivariate autoregressive model to determine the evolution of seizure dynamics in the [Formula: see text] Hz high frequency band across micro-domains sampled by such micro-electrode arrays. We showed that a directed transfer function (DTF) can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with known propagation pattern. We used seven complex partial seizures recorded from four patients undergoing intracranial monitoring for surgical evaluation to reconstruct the seizure propagation pattern over sliding windows using a DTF measure. We showed that a DTF can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with a known propagation pattern. In general, depending on the location of the micro-electrode grid with respect to the clinical SOZ and the time from seizure onset, ictal propagation changed in directional characteristics over a 2-10 s time scale, with gross directionality limited to spatial dimensions of approximately [Formula: see text]. It was also seen that the strongest seizure patterns in the high frequency band and their sources over such micro-domains are more stable over time and across seizures bordering the clinically determined SOZ than inside. This type of propagation analysis might in future provide an additional tool to epileptologists for characterizing epileptogenic tissue. This will potentially help narrowing down resection zones without compromising essential brain functions as well as provide important information about targeting anti-epileptic stimulation devices.

A study of the dynamics of seizure propagation across micro domains in the vicinity of the seizure onset zone

NASA Astrophysics Data System (ADS)

Basu, Ishita; Kudela, Pawel; Korzeniewska, Anna; Franaszczuk, Piotr J.; Anderson, William S.

2015-08-01

Objective. The use of micro-electrode arrays to measure electrical activity from the surface of the brain is increasingly being investigated as a means to improve seizure onset zone (SOZ) localization. In this work, we used a multivariate autoregressive model to determine the evolution of seizure dynamics in the 70-110 Hz high frequency band across micro-domains sampled by such micro-electrode arrays. We showed that a directed transfer function (DTF) can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with known propagation pattern. Approach. We used seven complex partial seizures recorded from four patients undergoing intracranial monitoring for surgical evaluation to reconstruct the seizure propagation pattern over sliding windows using a DTF measure. Main results. We showed that a DTF can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with a known propagation pattern. In general, depending on the location of the micro-electrode grid with respect to the clinical SOZ and the time from seizure onset, ictal propagation changed in directional characteristics over a 2-10 s time scale, with gross directionality limited to spatial dimensions of approximately 9 m{{m}2}. It was also seen that the strongest seizure patterns in the high frequency band and their sources over such micro-domains are more stable over time and across seizures bordering the clinically determined SOZ than inside. Significance. This type of propagation analysis might in future provide an additional tool to epileptologists for characterizing epileptogenic tissue. This will potentially help narrowing down resection zones without compromising essential brain functions as well as provide important information about targeting anti-epileptic stimulation devices.

Connectivity Predicts Deep Brain Stimulation Outcome in Parkinson Disease

PubMed Central

Horn, Andreas; Reich, Martin; Vorwerk, Johannes; Li, Ningfei; Wenzel, Gregor; Fang, Qianqian; Schmitz-Hübsch, Tanja; Nickl, Robert; Kupsch, Andreas; Volkmann, Jens; Kühn, Andrea A.; Fox, Michael D.

2018-01-01

Objective The benefit of deep brain stimulation (DBS) for Parkinson disease (PD) may depend on connectivity between the stimulation site and other brain regions, but which regions and whether connectivity can predict outcome in patients remain unknown. Here, we identify the structural and functional connectivity profile of effective DBS to the subthalamic nucleus (STN) and test its ability to predict outcome in an independent cohort. Methods A training dataset of 51 PD patients with STN DBS was combined with publicly available human connectome data (diffusion tractography and resting state functional connectivity) to identify connections reliably associated with clinical improvement (motor score of the Unified Parkinson Disease Rating Scale [UPDRS]). This connectivity profile was then used to predict outcome in an independent cohort of 44 patients from a different center. Results In the training dataset, connectivity between the DBS electrode and a distributed network of brain regions correlated with clinical response including structural connectivity to supplementary motor area and functional anticorrelation to primary motor cortex (p<0.001). This same connectivity profile predicted response in an independent patient cohort (p<0.01). Structural and functional connectivity were independent predictors of clinical improvement (p<0.001) and estimated response in individual patients with an average error of 15% UPDRS improvement. Results were similar using connectome data from normal subjects or a connectome age, sex, and disease matched to our DBS patients. Interpretation Effective STN DBS for PD is associated with a specific connectivity profile that can predict clinical outcome across independent cohorts. This prediction does not require specialized imaging in PD patients themselves. PMID:28586141

Posterolateral Trajectories Favor a Longer Motor Domain in Subthalamic Nucleus Deep Brain Stimulation for Parkinson Disease.

PubMed

Tamir, Idit; Marmor-Levin, Odeya; Eitan, Renana; Bergman, Hagai; Israel, Zvi

2017-10-01

The clinical outcome of patients with Parkinson disease (PD) who undergo subthalamic nucleus (STN) deep brain stimulation (DBS) is, in part, determined by the length of the electrode trajectory through the motor STN domain, the dorsolateral oscillatory region (DLOR). Trajectory length has been found to correlate with the stimulation-related improvement in patients' motor function (estimated by part III of the United Parkinson's Disease Rating Scale [UPDRS]). Therefore, it seems that ideally trajectories should have maximal DLOR length. We retrospectively studied the influence of various anatomic aspects of the brains of patients with PD and the geometry of trajectories planned on the length of the DLOR and STN recorded during DBS surgery. We examined 212 trajectories and 424 microelectrode recording tracks in 115 patients operated on in our center between 2010 and 2015. We found a strong correlation between the length of the recorded DLOR and STN. Trajectories that were more lateral and/or posterior in orientation had a longer STN and DLOR pass, although the DLOR/STN fraction length remained constant. The STN target was more lateral when the third ventricle was wider, and the latter correlated with older age and male gender. Trajectory angles correlate with the recorded STN and DLOR lengths, and should be altered toward a more posterolateral angle in older patients and atrophied brains to compensate for the changes in STN location and geometry. These fine adjustments should yield a longer motor domain pass, thereby improving the patient's predicted outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

Modeling bipolar stimulation of cardiac tissue

NASA Astrophysics Data System (ADS)

Galappaththige, Suran K.; Gray, Richard A.; Roth, Bradley J.

2017-09-01

Unipolar stimulation of cardiac tissue is often used in the design of cardiac pacemakers because of the low current required to depolarize the surrounding tissue at rest. However, the advantages of unipolar over bipolar stimulation are not obvious at shorter coupling intervals when the tissue near the pacing electrode is relatively refractory. Therefore, this paper analyzes bipolar stimulation of cardiac tissue. The strength-interval relationship for bipolar stimulation is calculated using the bidomain model and a recently developed parsimonious ionic current model. The strength-interval curves obtained using different electrode separations and arrangements (electrodes placed parallel to the fibers versus perpendicular to the fibers) indicate that bipolar stimulation results in more complex activation patterns compared to unipolar stimulation. An unusually low threshold stimulus current is observed when the electrodes are close to each other (a separation of 1 mm) because of break excitation. Unlike for unipolar stimulation, anode make excitation is not present during bipolar stimulation, and an abrupt switch from anode break to cathode make excitation can cause dramatic changes in threshold with very small changes in the interval. These results could impact the design of implantable pacemakers and defibrillators.

A testbed for optimizing electrodes embedded in the skull or in artificial skull replacement pieces used after injury

PubMed Central

Jiang, JingLe; Marathe, Amar R.; Keene, Jennifer C.; Taylor, Dawn M.

2016-01-01

Background Custom-fitted skull replacement pieces are often used after a head injury or surgery to replace damaged bone. Chronic brain recordings are beneficial after injury/surgery for monitoring brain health and seizure development. Embedding electrodes directly in these artificial skull replacement pieces would be a novel, low-risk way to perform chronic brain monitoring in these patients. Similarly, embedding electrodes directly in healthy skull would be a viable minimally-invasive option for many other neuroscience and neurotechnology applications requiring chronic brain recordings. New Method We demonstrate a preclinical testbed that can be used for refining electrode designs embedded in artificial skull replacement pieces or for embedding directly into the skull itself. Options are explored to increase the surface area of the contacts without increasing recording contact diameter to maximize recording resolution. Results Embedding electrodes in real or artificial skull allows one to lower electrode impedance without increasing the recording contact diameter by making use of conductive channels that extend into the skull. The higher density of small contacts embedded in the artificial skull in this testbed enables one to optimize electrode spacing for use in real bone. Comparison with Existing Methods For brain monitoring applications, skull-embedded electrodes fill a gap between electroencephalograms recorded on the scalp surface and the more invasive epidural or subdural electrode sheets. Conclusions Embedding electrodes into the skull or in skull replacement pieces may provide a safe, convenient, minimally-invasive alternative for chronic brain monitoring. The manufacturing methods described here will facilitate further testing of skull-embedded electrodes in animal models. PMID:27979758

A testbed for optimizing electrodes embedded in the skull or in artificial skull replacement pieces used after injury.

PubMed

Jiang, JingLe; Marathe, Amar R; Keene, Jennifer C; Taylor, Dawn M

2017-02-01

Custom-fitted skull replacement pieces are often used after a head injury or surgery to replace damaged bone. Chronic brain recordings are beneficial after injury/surgery for monitoring brain health and seizure development. Embedding electrodes directly in these artificial skull replacement pieces would be a novel, low-risk way to perform chronic brain monitoring in these patients. Similarly, embedding electrodes directly in healthy skull would be a viable minimally-invasive option for many other neuroscience and neurotechnology applications requiring chronic brain recordings. We demonstrate a preclinical testbed that can be used for refining electrode designs embedded in artificial skull replacement pieces or for embedding directly into the skull itself. Options are explored to increase the surface area of the contacts without increasing recording contact diameter to maximize recording resolution. Embedding electrodes in real or artificial skull allows one to lower electrode impedance without increasing the recording contact diameter by making use of conductive channels that extend into the skull. The higher density of small contacts embedded in the artificial skull in this testbed enables one to optimize electrode spacing for use in real bone. For brain monitoring applications, skull-embedded electrodes fill a gap between electroencephalograms recorded on the scalp surface and the more invasive epidural or subdural electrode sheets. Embedding electrodes into the skull or in skull replacement pieces may provide a safe, convenient, minimally-invasive alternative for chronic brain monitoring. The manufacturing methods described here will facilitate further testing of skull-embedded electrodes in animal models. Published by Elsevier B.V.

Recording and assessment of evoked potentials with electrode arrays.

PubMed

Miljković, N; Malešević, N; Kojić, V; Bijelić, G; Keller, T; Popović, D B

2015-09-01

In order to optimize procedure for the assessment of evoked potentials and to provide visualization of the flow of action potentials along the motor systems, we introduced array electrodes for stimulation and recording and developed software for the analysis of the recordings. The system uses a stimulator connected to an electrode array for the generation of evoked potentials, an electrode array connected to the amplifier, A/D converter and computer for the recording of evoked potentials, and a dedicated software application. The method has been tested for the assessment of the H-reflex on the triceps surae muscle in six healthy humans. The electrode array with 16 pads was positioned over the posterior aspect of the thigh, while the recording electrode array with 16 pads was positioned over the triceps surae muscle. The stimulator activated all the pads of the stimulation electrode array asynchronously, while the signals were recorded continuously at all the recording sites. The results are topography maps (spatial distribution of evoked potentials) and matrices (spatial visualization of nerve excitability). The software allows the automatic selection of the lowest stimulation intensity to achieve maximal H-reflex amplitude and selection of the recording/stimulation pads according to predefined criteria. The analysis of results shows that the method provides rich information compared with the conventional recording of the H-reflex with regard the spatial distribution.

Neuroimaging and cognitive changes during déjà vu.

PubMed

Kovacs, Norbert; Auer, Tibor; Balas, Istvan; Karadi, Kazmer; Zambo, Katalin; Schwarcz, Attila; Klivenyi, Peter; Jokeit, Hennric; Horvath, Krisztina; Nagy, Ferenc; Janszky, Jozsef

2009-01-01

The cause or the physiological role of déjà vu (DV) in healthy people is unknown. The pathophysiology of DV-type epileptic aura is also unresolved. Here we describe a 22-year-old woman treated with deep brain stimulation (DBS) of the left internal globus pallidus for hemidystonia. At certain stimulation settings, DBS elicited reproducible episodes of DV. Neuropsychological tests and single-photon-emission computed tomography (SPECT) were performed during DBS-evoked DV and during normal DBS stimulation without DV. SPECT during DBS-evoked DV revealed hyperperfusion of the right (contralateral to the electrode) hippocampus and other limbic structures. Neuropsychological examinations performed during several evoked DV episodes revealed disturbances in nonverbal memory. Our results confirm the role of mesiotemporal structures in the pathogenesis of DV. We hypothesize that individual neuroanatomy and disturbances in gamma oscillations or in the dopaminergic system played a role in DBS-elicited DV in our patient.

Surgical treatment of Parkinson’s disease: Past, present, and future

PubMed Central

Duker, Andrew P.; Espay, Alberto J.

2013-01-01

Advances in functional neurosurgery have expanded the treatment of Parkinson’s disease (PD), from early lesional procedures to targeted electrical stimulation of specific nodes in the basal ganglia circuitry. Deep brain stimulation (DBS), applied to selected patients with Parkinson’s disease (PD) and difficult-to-manage motor fluctuations, yields substantial reductions in off time and dyskinesia. Outcomes for DBS targeting the two major studied targets in PD, the subthalamic nucleus (STN) and the internal segment of the globus pallidus (GPi), appear to be broadly similar and the choice is best made based on individual patient factors and surgeon preference. Emerging concepts in DBS include examination of new targets, such as the potential efficacy of pedunculopontine nucleus (PPN) stimulation for treatment of freezing and falls, the utilization of pathologic oscillations in the beta band to construct an adaptive “closed-loop” DBS, and new technologies, including segmented electrodes to steer current toward specific neural populations. PMID:23896506

Ultrasound-guided, percutaneous peripheral nerve stimulation: technical note.

PubMed

Chan, Isaac; Brown, Anthony R; Park, Kenneth; Winfree, Christopher J

2010-09-01

Peripheral nerve stimulation is a form of neuromodulation that applies electric current to peripheral nerves to induce stimulation paresthesias within the painful areas. To report a method of ultrasound-guided, percutaneous peripheral nerve stimulation. This technique utilizes real-time imaging to avoid injury to adjacent vascular structures during minimally invasive placement of peripheral nerve stimulator electrodes. We describe a patient that presented with chronic, bilateral foot pain following multiple foot surgeries, for whom a comprehensive, pain management treatment strategy had failed. We utilized ultrasound-guided, percutaneous tibial nerve stimulation at a thigh level to provide durable pain relief on the right side, and open peripheral nerve stimulation on the left. The patient experienced appropriate stimulation paresthesias and excellent pain relief on the plantar aspect of the right foot with the percutaneous electrode. On the left side, we were unable to direct the stimulation paresthesias to the sole of the foot, despite multiple electrode repositionings. A subsequent, open placement of a left tibial nerve stimulator was performed. This revealed that the correct electrode position against the tibial nerve was immediately adjacent to the popliteal artery, and was thus not appropriate for percutaneous placement. We describe a method of ultrasound-guided peripheral nerve stimulation that avoids the invasiveness of electrode placement via an open procedure while providing excellent pain relief. We further describe limitations of the percutaneous approach when navigating close to large blood vessels, a situation more appropriately managed with open peripheral nerve stimulator placement. Ultrasound-guided placement may be considered for patients receiving peripheral nerve stimulators placed within the deep tissues, and not easily placed in a blind fashion.

Betting on DBS: Effects of Subthalamic Nucleus Deep Brain Stimulation on Risk-Taking and Decision-Making in Patients with Parkinson’s Disease

PubMed Central

Brandt, Jason; Rogerson, Mark; Al-Joudi, Haya; Reckess, Gila; Shpritz, Barnett; Umeh, Chizoba C.; Aljehani, Noha; Mills, Kelly; Mari, Zoltan

2014-01-01

Objective Concerns persist that deep brain stimulation (DBS) for Parkinson’s disease (PD) increases impulsivity and/or induces excessive reward-seeking. We report here the performance of PD patients with implanted subthalamic nucleus electrodes, with stimulation on and off, on three laboratory tasks of risk-taking and decision-making. They are compared to PD patients maintained on medication and normal control subjects. Methods and Results In the Game of Dice Task, a test of “risky” decision-making, PD patients with or without DBS made highest-risk bets more often, and ended up with less money, than normal controls. There was a trend for DBS stimulation to ameliorate this effect. Deal or No-Deal is an “ambiguous” decision-making task that assessed preference for risk (holding on to one’s briefcase) over a “sure thing” (accepting the banker’s offer). Here, DBS patients were more conservative with stimulation on than off. They accepted smaller offers from the banker and won less money in the DBS-on condition. Overall, the two PD groups won less money than healthy participants. The Framing Paradigm assessed willingness to gamble on a fixed (unambiguous) prize depending on whether the reward was “framed” as a loss or a gain. Nonsurgical PD patients tended to be more risk-averse than normal subjects, whereas DBS patients were more willing to gamble for gains as well as losses both on and off stimulation. Conclusions On “risky” decision-making tasks, DBS patients were more risk-taking than normal, but stimulation may temper this tendency. In contrast, in an “ambiguous risk” situation, DBS patients were more risk-averse (conservative) than normal, and this tendency was greatest with stimulation. PMID:25486385

Stimulation of the dorsal periaqueductal gray enhances spontaneous recovery of a conditioned taste aversion

PubMed Central

Mickley, G. Andrew; Ketchesin, Kyle D.; Ramos, Linnet; Luchsinger, Joseph R.; Rogers, Morgan M.; Wiles, Nathanael R.; Hoxha, Nita

2012-01-01

Due to its relevance to clinical practice, extinction of learned fears has been a major focus of recent research. However, less is known about the means by which conditioned fears re-emerge (i.e., spontaneously recover) as time passes or contexts change following extinction. The periaqueductal gray represents the final common pathway mediating defensive reactions to fear and we have reported previously that the dorsolateral PAG (dlPAG) exhibits a small but reliable increase in neural activity (as measured by c-fos protein immunoreactivity) when spontaneous recovery (SR) of a conditioned taste aversion (CTA) is reduced. Here we extend these correlational studies to determine if inducing dlPAG c-fos expression through electrical brain stimulation could cause a reduction in SR of a CTA. Male Sprague-Dawley rats acquired a strong aversion to saccharin (conditioned stimulus; CS) and then underwent CTA extinction through multiple non-reinforced exposures to the CS. Following a 30-day latency period after asymptotic extinction was achieved; rats either received stimulation of the dorsal PAG (dPAG) or stimulation of closely adjacent structures. Sixty minutes following the stimulation, rats were again presented with the saccharin solution as we tested for SR of the CTA. The brain stimulation evoked c-fos expression around the tip of the electrodes. However, stimulation of the dPAG failed to reduce SR of the previously extinguished CTA. In fact, dPAG stimulation caused rats to significantly suppress their saccharin drinking (relative to controls) – indicating an enhanced SR. These data refute a cause-and-effect relationship between enhanced dPAG c-fos expression and a reduction in SR. However, they highlight a role for the dPAG in modulating SR of extinguished CTAs. PMID:23183042

Betting on DBS: Effects of subthalamic nucleus deep brain stimulation on risk taking and decision making in patients with Parkinson's disease.

PubMed

Brandt, Jason; Rogerson, Mark; Al-Joudi, Haya; Reckess, Gila; Shpritz, Barnett; Umeh, Chizoba C; Aljehani, Noha; Mills, Kelly; Mari, Zoltan

2015-07-01

Concerns persist that deep brain stimulation (DBS) for Parkinson's disease (PD) increases impulsivity or induces excessive reward seeking. We report here the performance of PD patients with implanted subthalamic nucleus electrodes, with stimulation on and off, on 3 laboratory tasks of risk taking and decision making. They are compared with PD patients maintained on medication and healthy participants. In the Game of Dice Task, a test of "risky" decision making, PD patients with or without DBS made highest risk bets more often and ended up with less money than did healthy participants. There was a trend for DBS stimulation to ameliorate this effect. Deal or No-Deal is an "ambiguous" decision-making task that assessed preference for risk (holding on to one's briefcase) over a "sure thing" (accepting the banker's offer). Here, DBS patients were more conservative with stimulation on than with it off. They accepted smaller offers from the banker and won less money in the DBS-on condition. Overall, the 2 PD groups won less money than did healthy participants. The Framing Paradigm assessed willingness to gamble on a fixed (unambiguous) prize depending on whether the reward was "framed" as a loss or a gain. Nonsurgical PD patients tended to be more risk-averse than were healthy participants, whereas DBS patients were more willing to gamble for gains as well as losses both on and off stimulation. On risky decision-making tasks, DBS patients took more risks than did healthy participants, but stimulation may temper this tendency. In contrast, in an ambiguous-risk situation, DBS patients were more risk-averse (conservative) than were healthy participants, and this tendency was greatest with stimulation. (c) 2015 APA, all rights reserved).

A Suprachoroidal Electrical Retinal Stimulator Design for Long-Term Animal Experiments and In Vivo Assessment of Its Feasibility and Biocompatibility in Rabbits

PubMed Central

Zhou, J. A.; Woo, S. J.; Park, S. I.; Kim, E. T.; Seo, J. M.; Chung, H.; Kim, S. J.

2008-01-01

This article reports on a retinal stimulation system for long-term use in animal electrical stimulation experiments. The presented system consisted of an implantable stimulator which provided continuous electrical stimulation, and an external component which provided preset stimulation patterns and power to the implanted stimulator via a paired radio frequency (RF) coil. A rechargeable internal battery and a parameter memory component were introduced to the implanted retinal stimulator. As a result, the external component was not necessary during the stimulation mode. The inductive coil pair was used to pass the parameter data and to recharge the battery. A switch circuit was used to separate the stimulation mode from the battery recharging mode. The implantable stimulator was implemented with IC chips and the electronics, except for the stimulation electrodes, were hermetically packaged in a biocompatible metal case. A polyimide-based gold electrode array was used. Surgical implantation into rabbits was performed to verify the functionality and safety of this newly designed system. The electrodes were implanted in the suprachoroidal space. Evoked cortical potentials were recorded during electrical stimulation of the retina. Long-term follow-up using OCT showed no chorioretinal abnormality after implantation of the electrodes. PMID:18317521

A Wireless 32-Channel Implantable Bidirectional Brain Machine Interface

PubMed Central

Su, Yi; Routhu, Sudhamayee; Moon, Kee S.; Lee, Sung Q.; Youm, WooSub; Ozturk, Yusuf

2016-01-01

All neural information systems (NIS) rely on sensing neural activity to supply commands and control signals for computers, machines and a variety of prosthetic devices. Invasive systems achieve a high signal-to-noise ratio (SNR) by eliminating the volume conduction problems caused by tissue and bone. An implantable brain machine interface (BMI) using intracortical electrodes provides excellent detection of a broad range of frequency oscillatory activities through the placement of a sensor in direct contact with cortex. This paper introduces a compact-sized implantable wireless 32-channel bidirectional brain machine interface (BBMI) to be used with freely-moving primates. The system is designed to monitor brain sensorimotor rhythms and present current stimuli with a configurable duration, frequency and amplitude in real time to the brain based on the brain activity report. The battery is charged via a novel ultrasonic wireless power delivery module developed for efficient delivery of power into a deeply-implanted system. The system was successfully tested through bench tests and in vivo tests on a behaving primate to record the local field potential (LFP) oscillation and stimulate the target area at the same time. PMID:27669264

Intraoperative cortico-cortical evoked potentials for the evaluation of language function during brain tumor resection: initial experience with 13 cases.

PubMed

Saito, Taiichi; Tamura, Manabu; Muragaki, Yoshihiro; Maruyama, Takashi; Kubota, Yuichi; Fukuchi, Satoko; Nitta, Masayuki; Chernov, Mikhail; Okamoto, Saori; Sugiyama, Kazuhiko; Kurisu, Kaoru; Sakai, Kuniyoshi L; Okada, Yoshikazu; Iseki, Hiroshi

2014-10-01

The objective in the present study was to evaluate the usefulness of cortico-cortical evoked potentials (CCEP) monitoring for the intraoperative assessment of speech function during resection of brain tumors. Intraoperative monitoring of CCEP was applied in 13 patients (mean age 34 ± 14 years) during the removal of neoplasms located within or close to language-related structures in the dominant cerebral hemisphere. For this purpose strip electrodes were positioned above the frontal language area (FLA) and temporal language area (TLA), which were identified with direct cortical stimulation and/or preliminary mapping with the use of implanted chronic subdural grid electrodes. The CCEP response was defined as the highest observed negative peak in either direction of stimulation. In 12 cases the tumor was resected during awake craniotomy. An intraoperative CCEP response was not obtained in one case because of technical problems. In the other patients it was identified from the FLA during stimulation of the TLA (7 cases) and from the TLA during stimulation of the FLA (5 cases), with a mean peak latency of 83 ± 15 msec. During tumor resection the CCEP response was unchanged in 5 cases, decreased in 4, and disappeared in 3. Postoperatively, all 7 patients with a decreased or absent CCEP response after lesion removal experienced deterioration in speech function. In contrast, in 5 cases with an unchanged intraoperative CCEP response, speaking abilities after surgery were preserved at the preoperative level, except in one patient who experienced not dysphasia, but dysarthria due to pyramidal tract injury. This difference was statistically significant (p < 0.01). The time required to recover speech function was also significantly associated with the type of intraoperative change in CCEP recordings (p < 0.01) and was, on average, 1.8 ± 1.0, 5.5 ± 1.0, and 11.0 ± 3.6 months, respectively, if the response was unchanged, was decreased, or had disappeared. Monitoring CCEP is feasible during the resection of brain tumors affecting language-related cerebral structures. In the intraoperative evaluation of speech function, it can be a helpful adjunct or can be used in its direct assessment with cortical and subcortical mapping during awake craniotomy. It can also be used to predict the prognosis of language disorders after surgery and decide on the optimal resection of a neoplasm.

Qualities of Single Electrode Stimulation as a Function of Rate and Place of Stimulation with a Cochlear Implant

PubMed Central

Landsberger, David M.; Vermeire, Katrien; Claes, Annes; Van Rompaey, Vincent; Van de Heyning, Paul

2015-01-01

Objectives Although it has been previously shown that changes in temporal coding produce changes in pitch in all cochlear regions, research has suggested that temporal coding might be best encoded in relatively apical locations. We hypothesized that although temporal coding may provide useable information at any cochlear location, low rates of stimulation might provide better sound quality in apical regions that are more likely to encode temporal information in the normal ear. In the present study, sound qualities of single electrode pulse trains were scaled to provide insight into the combined effects of cochlear location and stimulation rate on sound quality. Design Ten long term users of MED-EL cochlear implants with 31 mm electrode arrays (Standard or FLEXSOFT) were asked to scale the sound quality of single electrode pulse trains in terms of how “Clean”, “Noisy”, “High”, and “Annoying” they sounded. Pulse trains were presented on most electrodes between 1 and 12 representing the entire range of the long electrode array at stimulation rates of 100, 150, 200, 400, or 1500 pulses per second. Results While high rates of stimulation are scaled as having a “Clean” sound quality across the entire array, only the most apical electrodes (typically 1 through 3) were considered “Clean” at low rates. Low rates on electrodes 6 through 12 were not rated as “Clean” while the low rate quality of electrodes 4 and 5 were typically in between. Scaling of “Noisy” responses provided an approximately inverse pattern as “Clean” responses. “High” responses show the trade-off between rate and place of stimulation on pitch. Because “High” responses did not correlate with “Clean” responses, subjects were not rating sound quality based on pitch. Conclusions If explicit temporal coding is to be provided in a cochlear implant, it is likely to sound better when provided apically. Additionally, the finding that low rates sound clean only at apical places of stimulation is consistent with previous findings that a change in rate of stimulation corresponds to an equivalent change in perceived pitch at apical locations. Collectively, the data strongly suggests that temporal coding with a cochlear implant is optimally provided by electrodes placed well into the second cochlear turn. PMID:26583480

Stochastic information transfer from cochlear implant electrodes to auditory nerve fibers

NASA Astrophysics Data System (ADS)

Gao, Xiao; Grayden, David B.; McDonnell, Mark D.

2014-08-01

Cochlear implants, also called bionic ears, are implanted neural prostheses that can restore lost human hearing function by direct electrical stimulation of auditory nerve fibers. Previously, an information-theoretic framework for numerically estimating the optimal number of electrodes in cochlear implants has been devised. This approach relies on a model of stochastic action potential generation and a discrete memoryless channel model of the interface between the array of electrodes and the auditory nerve fibers. Using these models, the stochastic information transfer from cochlear implant electrodes to auditory nerve fibers is estimated from the mutual information between channel inputs (the locations of electrodes) and channel outputs (the set of electrode-activated nerve fibers). Here we describe a revised model of the channel output in the framework that avoids the side effects caused by an "ambiguity state" in the original model and also makes fewer assumptions about perceptual processing in the brain. A detailed comparison of how different assumptions on fibers and current spread modes impact on the information transfer in the original model and in the revised model is presented. We also mathematically derive an upper bound on the mutual information in the revised model, which becomes tighter as the number of electrodes increases. We found that the revised model leads to a significantly larger maximum mutual information and corresponding number of electrodes compared with the original model and conclude that the assumptions made in this part of the modeling framework are crucial to the model's overall utility.

Chronic implantation of cuff electrodes on the pelvic nerve in rats is well tolerated and does not compromise afferent or efferent fibre functionality

NASA Astrophysics Data System (ADS)

Crook, J. J.; Brouillard, C. B. J.; Irazoqui, P. P.; Lovick, T. A.

2018-04-01

Objective. Neuromodulation of autonomic nerve activity to regulate physiological processes is an emerging field. Vagal stimulation has received most attention whereas the potential of modulate visceral function by targeting autonomic nerves within the abdominal cavity remains under-exploited. Surgery to locate intra-abdominal targets is inherently more stressful than for peripheral nerves. Electrode leads risk becoming entrapped by intestines and loss of functionality in the nerve-target organ connection could result from electrode migration or twisting. Since nociceptor afferents are intermingled with similar-sized visceral autonomic fibres, stimulation may induce pain. In anaesthetised rats high frequency stimulation of the pelvic nerve can suppress urinary voiding but it is not known how conscious animals would react to this procedure. Our objective therefore was to determine how rats tolerated chronic implantation of cuff electrodes on the pelvic nerve, whether nerve stimulation would be aversive and whether nerve-bladder functionality would be compromised. Approach. We carried out a preliminary de-risking study to investigate how conscious rats tolerated chronic implantation of electrodes on the pelvic nerve, their responsiveness to intermittent high frequency stimulation and whether functionality of the nerve-bladder connection became compromised. Main results. Implantation of cuff electrodes was well-tolerated. The normal diurnal pattern of urinary voiding was not disrupted. Pelvic nerve stimulation (up to 4 mA, 3 kHz) for 30 min periods evoked mild alerting at stimulus onset but no signs of pain. Stimulation evoked a modest (<0.5 °C) increase in nerve temperature but the functional integrity of the nerve-bladder connection, reflected by contraction of the detrusor muscle in response to 10 Hz nerve stimulation, was not compromised. Significance. Chronic implantation of cuff electrodes on the pelvic nerve was found to be a well-tolerated procedure in rats and high frequency stimulation did not lead to loss of nerve functionality. Pelvic nerve stimulation has development potential for normalizing voiding dysfunction in conscious rats.

Flexible multichannel vagus nerve electrode for stimulation and recording for heart failure treatment.

PubMed

Xue, Ning; Martinez, Ignacio Delgado; Sun, Jianhai; Cheng, Yuhua; Liu, Chunxiu

2018-07-30

Vagus nerve stimulation is an emerging bioelectronic medicine to modulate cardiac function, as the nerve provides parasympathetic innervation to the heart. In this study, we developed a polyimide based 2D cuff electrode to wrap around on the vagus nerve. Thanks to the tiny size and bendable protruding structure of the contact tips of the device, the electrode sites are able to flexibly bend to touch the nerve, selectively record and stimulate the vagus nerve. Gold, platinum and platinum black materials were chosen to compose the electrodes for nerve stimulation and recording, respectively. Since the platinum black has ~30 times larger charge delivery capacity (CDC) than gold, Pt black electrode is used for nerve stimulation. The electrochemical impedance spectroscopy and cyclic voltammetry measurement of the three materials were conducted in vitro, revealing the results of 405 kΩ, 41 kΩ, 10.5 kΩ, @1 kHz and 0.81 mC/cm 2 , 4.26 mC/cm 2 , 25.5 mC/cm 2 , respectively (n = 3). The cuff electrodes were implanted into the right-sided vagus nerve of rats for in vivo experiment. Biphasic current configuration was implemented for nerve stimulation with frequency of 10 Hz, pulse during of 300 μs and various currents stimulus. The result shows the heart beat frequency drops up to 36% during the stimulation and was able to return the regular frequency as stimulation was removed. Subsequently, the vagus nerve signals were recorded with the four channel cuff electrodes. The magnitude of the compound nerve action potentials (CNAPs) is ~10 μV and the signal to noise ratio (SNR) is ~20. Copyright © 2018 Elsevier B.V. All rights reserved.

Creating virtual electrodes with 2D current steering

NASA Astrophysics Data System (ADS)

Spencer, Thomas C.; Fallon, James B.; Shivdasani, Mohit N.

2018-06-01

Objective. Current steering techniques have shown promise in retinal prostheses as a way to increase the number of distinct percepts elicitable without increasing the number of implanted electrodes. Previously, it has been shown that ‘virtual’ electrodes can be created between simultaneously stimulated electrode pairs, producing unique cortical response patterns. This study investigated whether virtual electrodes could be created using 2D current steering, and whether these virtual electrodes can produce cortical responses with predictable spatial characteristics. Approach. Normally-sighted eyes of seven adult anaesthetised cats were implanted with a 42-channel electrode array in the suprachoroidal space and multi-unit neural activity was recorded from the visual cortex. Stimuli were delivered to individual physical electrodes, or electrodes grouped into triangular, rectangular, and hexagonal arrangements. Varying proportions of charge were applied to each electrode in a group to ‘steer’ current and create virtual electrodes. The centroids of cortical responses to stimulation of virtual electrodes were compared to those evoked by stimulation of single physical electrodes. Main results. Responses to stimulation of groups of up to six electrodes with equal ratios of charge on each electrode resulted in cortical activation patterns that were similar to those elicited by the central physical electrode (centroids: RM ANOVA on ranks, p  >  0.05 neural spread: one-way ANOVA on Ranks, p  >  0.05). We were also able to steer the centroid of activation towards the direction of any of the electrodes of the group by applying a greater charge to that electrode, but the movement in the centroid was not found to be significant. Significance. The results suggest that current steering is possible in two dimensions between up to at least six electrodes, indicating it may be possible to increase the number of percepts in patients without increasing the number of physical electrodes. Being able to reproduce spatial characteristics of responses to individual physical electrodes suggests that this technique could also be used to compensate for faulty electrodes.

Brain stimulation modulates the autonomic nervous system, rating of perceived exertion and performance during maximal exercise.

PubMed

Okano, Alexandre Hideki; Fontes, Eduardo Bodnariuc; Montenegro, Rafael Ayres; Farinatti, Paulo de Tarso Veras; Cyrino, Edilson Serpeloni; Li, Li Min; Bikson, Marom; Noakes, Timothy David

2015-09-01

The temporal and insular cortex (TC, IC) have been associated with autonomic nervous system (ANS) control and the awareness of emotional feelings from the body. Evidence shows that the ANS and rating of perceived exertion (RPE) regulate exercise performance. Non-invasive brain stimulation can modulate the cortical area directly beneath the electrode related to ANS and RPE, but it could also affect subcortical areas by connection within the cortico-cortical neural networks. This study evaluated the effects of transcranial direct current stimulation (tDCS) over the TC on the ANS, RPE and performance during a maximal dynamic exercise. Ten trained cyclists participated in this study (33±9 years; 171.5±5.8 cm; 72.8±9.5 kg; 10-11 training years). After 20-min of receiving either anodal tDCS applied over the left TC (T3) or sham stimulation, subjects completed a maximal incremental cycling exercise test. RPE, heart rate (HR) and R-R intervals (as a measure of ANS function) were recorded continuously throughout the tests. Peak power output (PPO) was recorded at the end of the tests. With anodal tDCS, PPO improved by ~4% (anodal tDCS: 313.2±29.9 vs 301.0±19.8 watts: sham tDCS; p=0.043), parasympathetic vagal withdrawal was delayed (anodal tDCS: 147.5±53.3 vs 125.0±35.4 watts: sham tDCS; p=0.041) and HR was reduced at submaximal workloads. RPE also increased more slowly during exercise following anodal tDCS application, but maximal RPE and HR values were not affected by cortical stimulation. The findings suggest that non-invasive brain stimulation over the TC modulates the ANS activity and the sensory perception of effort and exercise performance, indicating that the brain plays a crucial role in the exercise performance regulation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Transcranial Electrical Neuromodulation Based on the Reciprocity Principle

PubMed Central

Fernández-Corazza, Mariano; Turovets, Sergei; Luu, Phan; Anderson, Erik; Tucker, Don

2016-01-01

A key challenge in multi-electrode transcranial electrical stimulation (TES) or transcranial direct current stimulation (tDCS) is to find a current injection pattern that delivers the necessary current density at a target and minimizes it in the rest of the head, which is mathematically modeled as an optimization problem. Such an optimization with the Least Squares (LS) or Linearly Constrained Minimum Variance (LCMV) algorithms is generally computationally expensive and requires multiple independent current sources. Based on the reciprocity principle in electroencephalography (EEG) and TES, it could be possible to find the optimal TES patterns quickly whenever the solution of the forward EEG problem is available for a brain region of interest. Here, we investigate the reciprocity principle as a guideline for finding optimal current injection patterns in TES that comply with safety constraints. We define four different trial cortical targets in a detailed seven-tissue finite element head model, and analyze the performance of the reciprocity family of TES methods in terms of electrode density, targeting error, focality, intensity, and directionality using the LS and LCMV solutions as the reference standards. It is found that the reciprocity algorithms show good performance comparable to the LCMV and LS solutions. Comparing the 128 and 256 electrode cases, we found that use of greater electrode density improves focality, directionality, and intensity parameters. The results show that reciprocity principle can be used to quickly determine optimal current injection patterns in TES and help to simplify TES protocols that are consistent with hardware and software availability and with safety constraints. PMID:27303311

Transcranial Electrical Neuromodulation Based on the Reciprocity Principle.

PubMed

Fernández-Corazza, Mariano; Turovets, Sergei; Luu, Phan; Anderson, Erik; Tucker, Don

2016-01-01

A key challenge in multi-electrode transcranial electrical stimulation (TES) or transcranial direct current stimulation (tDCS) is to find a current injection pattern that delivers the necessary current density at a target and minimizes it in the rest of the head, which is mathematically modeled as an optimization problem. Such an optimization with the Least Squares (LS) or Linearly Constrained Minimum Variance (LCMV) algorithms is generally computationally expensive and requires multiple independent current sources. Based on the reciprocity principle in electroencephalography (EEG) and TES, it could be possible to find the optimal TES patterns quickly whenever the solution of the forward EEG problem is available for a brain region of interest. Here, we investigate the reciprocity principle as a guideline for finding optimal current injection patterns in TES that comply with safety constraints. We define four different trial cortical targets in a detailed seven-tissue finite element head model, and analyze the performance of the reciprocity family of TES methods in terms of electrode density, targeting error, focality, intensity, and directionality using the LS and LCMV solutions as the reference standards. It is found that the reciprocity algorithms show good performance comparable to the LCMV and LS solutions. Comparing the 128 and 256 electrode cases, we found that use of greater electrode density improves focality, directionality, and intensity parameters. The results show that reciprocity principle can be used to quickly determine optimal current injection patterns in TES and help to simplify TES protocols that are consistent with hardware and software availability and with safety constraints.

Capacitor electrode stimulates nerve or muscle without oxidation-reduction reactions.

PubMed

Guyton, D L; Hambrecht, F T

1973-07-06

Porous tantalum disks, available as "slugs" from the capacitor industry, have large available surface area and a thin insulating coating of tantalum pentoxide. When implanted, they fill with extracellular fluid and operate as capacitor-stimulating electrodes having high capacitance per unit volume. Capable of stimulating excitable tissute without generating electrochemical by-products, these electrodes should provide a safer interface between neural prosthetic devices and human tissue.

Active books: the design of an implantable stimulator that minimizes cable count using integrated circuits very close to electrodes.

PubMed

Liu, Xiao; Demosthenous, Andreas; Vanhoestenberghe, Anne; Jiang, Dai; Donaldson, Nick

2012-06-01

This paper presents an integrated stimulator that can be embedded in implantable electrode books for interfacing with nerve roots at the cauda equina. The Active Book overcomes the limitation of conventional nerve root stimulators which can only support a small number of stimulating electrodes due to cable count restriction through the dura. Instead, a distributed stimulation system with many tripole electrodes can be configured using several Active Books which are addressed sequentially. The stimulator was fabricated in a 0.6-μm high-voltage CMOS process and occupies a silicon area of 4.2 × 6.5 mm(2). The circuit was designed to deliver up to 8 mA stimulus current to tripole electrodes from an 18 V power supply. Input pad count is limited to five (two power and three control lines) hence requiring a specific procedure for downloading stimulation commands to the chip and extracting information from it. Supported commands include adjusting the amplitude of stimulus current, varying the current ratio at the two anodes in each channel, and measuring relative humidity inside the chip package. In addition to stimulation mode, the chip supports quiescent mode, dissipating less than 100 nA current from the power supply. The performance of the stimulator chip was verified with bench tests including measurements using tripoles in saline.

A foldable electrode array for 3D recording of deep-seated abnormal brain cavities

NASA Astrophysics Data System (ADS)

Kil, Dries; De Vloo, Philippe; Fierens, Guy; Ceyssens, Frederik; Hunyadi, Borbála; Bertrand, Alexander; Nuttin, Bart; Puers, Robert

2018-06-01

Objective. This study describes the design and microfabrication of a foldable thin-film neural implant and investigates its suitability for electrical recording of deep-lying brain cavity walls. Approach. A new type of foldable neural electrode array is presented, which can be inserted through a cannula. The microfabricated electrode is specifically designed for electrical recording of the cavity wall of thalamic lesions resulting from stroke. The proof-of-concept is demonstrated by measurements in rat brain cavities. On implantation, the electrode array unfolds in the brain cavity, contacting the cavity walls and allowing recording at multiple anatomical locations. A three-layer microfabrication process based on UV-lithography and Reactive Ion Etching is described. Electrochemical characterization of the electrode is performed in addition to an in vivo experiment in which the implantation procedure and the unfolding of the electrode are tested and visualized. Main results. Electrochemical characterization validated the suitability of the electrode for in vivo use. CT imaging confirmed the unfolding of the electrode in the brain cavity and analysis of recorded local field potentials showed the ability to record neural signals of biological origin. Significance. The conducted research confirms that it is possible to record neural activity from the inside wall of brain cavities at various anatomical locations after a single implantation procedure. This opens up possibilities towards research of abnormal brain cavities and the clinical conditions associated with them, such as central post-stroke pain.

Chronic intracortical microstimulation (ICMS) of cat sensory cortex using the Utah Intracortical Electrode Array.

PubMed

Rousche, P J; Normann, R A

1999-03-01

In an effort to assess the safety and efficacy of focal intracortical microstimulation (ICMS) of cerebral cortex with an array of penetrating electrodes as might be applied to a neuroprosthetic device to aid the deaf or blind, we have chronically implanted three trained cats in primary auditory cortex with the 100-electrode Utah Intracortical Electrode Array (UIEA). Eleven of the 100 electrodes were hard-wired to a percutaneous connector for chronic access. Prior to implant, cats were trained to "lever-press" in response to pure tone auditory stimulation. After implant, this behavior was transferred to "lever-presses" in response to current injections via single electrodes of the implanted arrays. Psychometric function curves relating injected charge level to the probability of response were obtained for stimulation of 22 separate electrodes in the three implanted cats. The average threshold charge/phase required for electrical stimulus detection in each cat was, 8.5, 8.6, and 11.6 nC/phase respectively, with a maximum charge/phase of 26 nC/phase and a minimum of 1.5 nC/phase thresholds were tracked for varying time intervals, and seven electrodes from two cats were tracked for up to 100 days. Electrodes were stimulated for no more than a few minutes each day. Neural recordings taken from the same electrodes before and after multiple electrical stimulation sessions were very similar in signal/noise ratio and in the number of recordable units, suggesting that the range of electrical stimulation levels used did not damage neurons in the vicinity of the electrodes. Although a few early implants failed, we conclude that ICMS of cerebral cortex to evoke a behavioral response can be achieved with the penetrating UIEA. Further experiments in support of a sensory cortical prosthesis based on ICMS are warranted.

Motor cortex stimulation and neuropathic pain: how does motor cortex stimulation affect pain-signaling pathways?

PubMed

Kim, Jinhyung; Ryu, Sang Baek; Lee, Sung Eun; Shin, Jaewoo; Jung, Hyun Ho; Kim, Sung June; Kim, Kyung Hwan; Chang, Jin Woo

2016-03-01

Neuropathic pain is often severe. Motor cortex stimulation (MCS) is used for alleviating neuropathic pain, but the mechanism of action is still unclear. This study aimed to understand the mechanism of action of MCS by investigating pain-signaling pathways, with the expectation that MCS would regulate both descending and ascending pathways. Neuropathic pain was induced in Sprague-Dawley rats. Surface electrodes for MCS were implanted in the rats. Tactile allodynia was measured by behavioral testing to determine the effect of MCS. For the pathway study, immunohistochemistry was performed to investigate changes in c-fos and serotonin expression; micro-positron emission tomography (mPET) scanning was performed to investigate changes of glucose uptake; and extracellular electrophysiological recordings were performed to demonstrate brain activity. MCS was found to modulate c-fos and serotonin expression. In the mPET study, altered brain activity was observed in the striatum, thalamic area, and cerebellum. In the electrophysiological study, neuronal activity was increased by mechanical stimulation and suppressed by MCS. After elimination of artifacts, neuronal activity was demonstrated in the ventral posterolateral nucleus (VPL) during electrical stimulation. This neuronal activity was effectively suppressed by MCS. This study demonstrated that MCS effectively attenuated neuropathic pain. MCS modulated ascending and descending pain pathways. It regulated neuropathic pain by affecting the striatum, periaqueductal gray, cerebellum, and thalamic area, which are thought to regulate the descending pathway. MCS also appeared to suppress activation of the VPL, which is part of the ascending pathway.

Thalamic deep brain stimulation decelerates automatic lexical activation.

PubMed

Ehlen, Felicitas; Vonberg, Isabelle; Tiedt, Hannes O; Horn, Andreas; Fromm, Ortwin; Kühn, Andrea A; Klostermann, Fabian

2017-02-01

Deep Brain Stimulation (DBS) of the thalamic ventral intermediate nucleus (VIM) is a therapeutic option for patients with essential tremor. Despite a generally low risk of side effects, declines in verbal fluency (VF) have previously been reported. We aimed to specify effects of VIM-DBS on major cognitive operations needed for VF task performance, represented by clusters and switches. Clusters are word production spurts, thought to arise from automatic activation of associated information pertaining to a given lexical field. Switches are slow word-to-word transitions, presumed to indicate controlled operations for stepping from one lexical field to another. Thirteen essential tremor patients with VIM-DBS performed verbal fluency tasks in their VIM-DBS ON and OFF conditions. Clusters and switches were formally defined by mathematical criteria. All results were compared to those of fifteen healthy control subjects, and significant OFF-ON-change scores were correlated to stimulation parameters. Patients produced fewer words than healthy controls. DBS ON compared to DBS OFF aggravated this deficit by prolonging the intervals between words within clusters, whereas switches remained unaffected. This stimulation effect correlated with more anterior electrode positions. VIM-DBS seems to influence word output dynamics during verbal fluency tasks on the level of word clustering. This suggests a perturbation of automatic lexical co-activation by thalamic stimulation, particularly if delivered relatively anteriorly. The findings are discussed in the context of the hypothesized role of the thalamus in lexical processing. Copyright © 2016 Elsevier Inc. All rights reserved.

Low Frequency Stimulation Decreases Seizure Activity in a Mutation Model of Epilepsy

PubMed Central

Kile, Kara Buehrer; Tian, Nan; Durand, Dominique M.

2013-01-01

Summary Purpose To investigate brain electrical activity in Q54 mice that display spontaneous seizures because of a gain-of-function mutation of the Scn2a sodium channel gene, and to evaluate the efficacy of low frequency deep brain stimulation (DBS) for seizure frequency reduction. Methods EEG, EMG, and hippocampal deep electrodes were implanted into Q54 mice expressing an epileptic phenotype (n = 6). Chronic six channel recordings (wideband, 0.1–300 Hz) were stored 24 hours a day for more than 12 days. Low Frequency stimulation (LFS) (3Hz, square wave, biphasic, 100μs, 400μA) was applied to the ventral hippocampal commisure (VHC) in alternating five minute cycles (on or off) 24 hours a day for a period of four days. Results LFS (3Hz) resulted in a significant reduction in seizure frequency and duration (21% and 35%, p<0.05), when applied to the VHC of epileptic Q54 mice (n = 6). Seizure frequency was not directly affected by stimulation state (“on” versus “off”). Conclusion LFS applied at a frequency of 3Hz significantly reduced seizure frequency and duration in the Q54 model. Furthermore, the reduction of seizure frequency and duration by LFS was not immediate but had a delayed and lasting effect, supporting complex, indirect mechanisms of action. PMID:20659150

Subcortical roles in lexical task processing: Inferences from thalamic and subthalamic event-related potentials.

PubMed

Tiedt, Hannes O; Ehlen, Felicitas; Krugel, Lea K; Horn, Andreas; Kühn, Andrea A; Klostermann, Fabian

2017-01-01

Subcortical functions for language capacities are poorly defined, but may be investigated in the context of deep brain stimulation. Here, we studied event-related potentials recorded from electrodes in the subthalamic nucleus (STN) and the thalamic ventral intermediate nucleus (VIM) together with surface-EEG. Participants completed a lexical decision task (LDT), which required the differentiation of acoustically presented words from pseudo-words by button press. Target stimuli were preceded by prime-words. In recordings from VIM, a slow potential shift apparent at the lower electrode contacts persisted during target stimulus presentation (equally for words and pseudo-words). In contrast, recordings from STN electrodes showed a short local activation on prime-words but not target-stimuli. In both depth-recording regions, further components related to contralateral motor responses to target words were evident. On scalp level, mid-central activations on (pseudo)lexical stimuli were obtained, in line with the expression of N400 potentials. The prolonged activity recorded from VIM, exclusively accompanying the relevant LDT phase, is in line with the idea of thalamic "selective engagement" for supporting the realization of the behavioral focus demanded by the task. In contrast, the phasic prime related activity rather indicates "procedural" STN functions, for example, for trial sequencing or readiness inhibition of prepared target reactions. Hum Brain Mapp 38:370-383, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Stimulation of the nervous system for the management of seizures: current and future developments.

PubMed

Murphy, Jerome V; Patil, Arunangelo

2003-01-01

Vagal nerve stimulation (VNS) for the treatment of refractory epilepsy appears to have started from the theory that since VNS can alter the EEG, it may influence epilepsy. It proved effective in several models of epilepsy and was then tried in short-term, open-label and double-blind trials, leading to approval in Canada, Europe and the US. Follow-up observations in these patients demonstrated continued improvement in seizure control for up to 2 years. Close to 50% of treated patients have achieved at least a 50% reduction in seizure frequency. This therapy was also useful as rescue therapy for ongoing seizures in some patients; many patients are more alert. The initial trials were completed in patients >/=12 years of age with refractory partial seizures. Subsequently, similar benefits were shown in patients with tuberous sclerosis complex, Lennox-Gastaut syndrome, hypothalamic hamartomas and primary generalised seizures. Implanting the generator and leads is technically easy, and complications are few. The method of action is largely unknown, although VNS appears to alter metabolic activity in specific brain nuclei. Considering that improvement in mood is frequently found in patients using VNS, it has undergone trials in patients with depression. Other illnesses deserving exploration with this unusual therapy are Alzheimer's disease and autism. Some aspects of VNS have proven disappointing. Although patients have fewer seizures, the number of antiepileptic drugs they take is not significantly reduced. In addition, there is no way to accurately predict the end of life of the generator. Optimal stimulation parameters, if they exist, are unknown. Deep brain stimulation is a new method for controlling medically refractory seizures. It is based on the observation that thalamic stimulation can influence the EEG over a wide area. Several thalamic nuclei have been the object of stimulation in different groups of patients. Intraoperative brain imaging is essential for electrode placement. The procedure is done under local anaesthesia. Experience with this therapy is currently limited, but growing.

Physiological and modeling evidence for focal transcranial electrical brain stimulation in humans: A basis for high-definition tDCS

PubMed Central

Edwards, Dylan; Cortes, Mar; Datta, Abhishek; Minhas, Preet; Wassermann, Eric M.; Bikson, Marom

2015-01-01

Transcranial Direct Current Stimulation (tDCS) is a non-invasive, low-cost, well-tolerated technique producing lasting modulation of cortical excitability. Behavioral and therapeutic outcomes of tDCS are linked to the targeted brain regions, but there is little evidence that current reaches the brain as intended. We aimed to: (1) validate a computational model for estimating cortical electric fields in human transcranial stimulation, and (2) assess the magnitude and spread of cortical electric field with a novel High-Definition tDCS (HD-tDCS) scalp montage using a 4×1-Ring electrode configuration. In three healthy adults, Transcranial Electrical Stimulation (TES) over primary motor cortex (M1) was delivered using the 4×1 montage (4× cathode, surrounding a single central anode; montage radius ~3 cm) with sufficient intensity to elicit a discrete muscle twitch in the hand. The estimated current distribution in M1 was calculated using the individualized MRI-based model, and compared with the observed motor response across subjects. The response magnitude was quantified with stimulation over motor cortex as well as anterior and posterior to motor cortex. In each case the model data were consistent with the motor response across subjects. The estimated cortical electric fields with the 4×1 montage were compared (area, magnitude, direction) for TES and tDCS in each subject. We provide direct evidence in humans that TES with a 4×1-Ring configuration can activate motor cortex and that current does not substantially spread outside the stimulation area. Computational models predict that both TES and tDCS waveforms using the 4×1-Ring configuration generate electric fields in cortex with comparable gross current distribution, and preferentially directed normal (inward) currents. The agreement of modeling and experimental data for both current delivery and focality support the use of the HD-tDCS 4×1-Ring montage for cortically targeted neuromodulation. PMID:23370061

Novel fingerprinting method characterises the necessary and sufficient structural connectivity from deep brain stimulation electrodes for a successful outcome

NASA Astrophysics Data System (ADS)

Fernandes, Henrique M.; Van Hartevelt, Tim J.; Boccard, Sandra G. J.; Owen, Sarah L. F.; Cabral, Joana; Deco, Gustavo; Green, Alex L.; Fitzgerald, James J.; Aziz, Tipu Z.; Kringelbach, Morten L.

2015-01-01

Deep brain stimulation (DBS) is a remarkably effective clinical tool, used primarily for movement disorders. DBS relies on precise targeting of specific brain regions to rebalance the oscillatory behaviour of whole-brain neural networks. Traditionally, DBS targeting has been based upon animal models (such as MPTP for Parkinson’s disease) but has also been the result of serendipity during human lesional neurosurgery. There are, however, no good animal models of psychiatric disorders such as depression and schizophrenia, and progress in this area has been slow. In this paper, we use advanced tractography combined with whole-brain anatomical parcellation to provide a rational foundation for identifying the connectivity ‘fingerprint’ of existing, successful DBS targets. This knowledge can then be used pre-surgically and even potentially for the discovery of novel targets. First, using data from our recent case series of cingulate DBS for patients with treatment-resistant chronic pain, we demonstrate how to identify the structural ‘fingerprints’ of existing successful and unsuccessful DBS targets in terms of their connectivity to other brain regions, as defined by the whole-brain anatomical parcellation. Second, we use a number of different strategies to identify the successful fingerprints of structural connectivity across four patients with successful outcomes compared with two patients with unsuccessful outcomes. This fingerprinting method can potentially be used pre-surgically to account for a patient’s individual connectivity and identify the best DBS target. Ultimately, our novel fingerprinting method could be combined with advanced whole-brain computational modelling of the spontaneous dynamics arising from the structural changes in disease, to provide new insights and potentially new targets for hitherto impenetrable neuropsychiatric disorders.

Assessment of variability in cerebral vasculature for neuro-anatomical surgery planning in rodent brain

NASA Astrophysics Data System (ADS)

Rangarajan, J. R.; Van Kuyck, K.; Himmelreich, U.; Nuttin, B.; Maes, F.; Suetens, P.

2011-03-01

Clinical and pre-clinical studies show that deep brain stimulation (DBS) of targeted brain regions by neurosurgical techniques ameliorate psychiatric disorder such as anorexia nervosa. Neurosurgical interventions in preclinical rodent brain are mostly accomplished manually with a 2D atlas. Considering both the large number of animals subjected to stereotactic surgical experiments and the associated imaging cost, feasibility of sophisticated pre-operative imaging based surgical path planning and/or robotic guidance is limited. Here, we spatially normalize vasculature information and assess the intra-strain variability in cerebral vasculature for a neurosurgery planning. By co-registering and subsequently building a probabilistic vasculature template in a standard space, we evaluate the risk of a user defined electrode trajectory damaging a blood vessel on its path. The use of such a method may not only be confined to DBS therapy in small animals, but also could be readily applicable to a wide range of stereotactic small animal surgeries like targeted injection of contrast agents and cell labeling applications.

On the single sweep processing of auditory brainstem responses: click vs. chirp stimulations and active vs. passive electrodes.

PubMed

Corona-Strauss, Farah I; Delb, Wolfgang; Bloching, Marc; Strauss, Daniel J

2008-01-01

We have recently shown that click evoked auditory brainstem responses (ABRs) single sweeps can efficiently be processed by a hybrid novelty detection system. This approach allowed for the objective detection of hearing thresholds in a fraction of time of conventional schemes, making it appropriate for the efficient implementation of newborn hearing screening procedures. It is the objective of this study to evaluate whether this approach might further be improved by different stimulation paradigms and electrode settings. In particular, we evaluate chirp stimulations which compensate the basilar-membrane dispersion and active electrodes which are less sensitive to movements. This is the first study which is directed to a single sweep processing of chirp evoked ABRs. By concentrating on transparent features and a minimum number of adjustable parameters, we present an objective comparison of click vs.chirp stimulations and active vs. passive electrodes in the ultrafast ABR detection. We show that chirp evoked brainstem responses and active electrodes might improve the single sweeps analysis of ABRs.Consequently, we conclude that a single sweep processing of ABRs for the objective determination of hearing thresholds can further be improved by the use of optimized chirp stimulations and active electrodes.

Nanostructured cavity devices for extracellular stimulation of HL-1 cells

NASA Astrophysics Data System (ADS)

Czeschik, Anna; Rinklin, Philipp; Derra, Ulrike; Ullmann, Sabrina; Holik, Peter; Steltenkamp, Siegfried; Offenhäusser, Andreas; Wolfrum, Bernhard

2015-05-01

Microelectrode arrays (MEAs) are state-of-the-art devices for extracellular recording and stimulation on biological tissue. Furthermore, they are a relevant tool for the development of biomedical applications like retina, cochlear and motor prostheses, cardiac pacemakers and drug screening. Hence, research on functional cell-sensor interfaces, as well as the development of new surface structures and modifications for improved electrode characteristics, is a vivid and well established field. However, combining single-cell resolution with sufficient signal coupling remains challenging due to poor cell-electrode sealing. Furthermore, electrodes with diameters below 20 µm often suffer from a high electrical impedance affecting the noise during voltage recordings. In this study, we report on a nanocavity sensor array for voltage-controlled stimulation and extracellular action potential recordings on cellular networks. Nanocavity devices combine the advantages of low-impedance electrodes with small cell-chip interfaces, preserving a high spatial resolution for recording and stimulation. A reservoir between opening aperture and electrode is provided, allowing the cell to access the structure for a tight cell-sensor sealing. We present the well-controlled fabrication process and the effect of cavity formation and electrode patterning on the sensor's impedance. Further, we demonstrate reliable voltage-controlled stimulation using nanostructured cavity devices by capturing the pacemaker of an HL-1 cell network.Microelectrode arrays (MEAs) are state-of-the-art devices for extracellular recording and stimulation on biological tissue. Furthermore, they are a relevant tool for the development of biomedical applications like retina, cochlear and motor prostheses, cardiac pacemakers and drug screening. Hence, research on functional cell-sensor interfaces, as well as the development of new surface structures and modifications for improved electrode characteristics, is a vivid and well established field. However, combining single-cell resolution with sufficient signal coupling remains challenging due to poor cell-electrode sealing. Furthermore, electrodes with diameters below 20 µm often suffer from a high electrical impedance affecting the noise during voltage recordings. In this study, we report on a nanocavity sensor array for voltage-controlled stimulation and extracellular action potential recordings on cellular networks. Nanocavity devices combine the advantages of low-impedance electrodes with small cell-chip interfaces, preserving a high spatial resolution for recording and stimulation. A reservoir between opening aperture and electrode is provided, allowing the cell to access the structure for a tight cell-sensor sealing. We present the well-controlled fabrication process and the effect of cavity formation and electrode patterning on the sensor's impedance. Further, we demonstrate reliable voltage-controlled stimulation using nanostructured cavity devices by capturing the pacemaker of an HL-1 cell network. Electronic supplementary information (ESI) available: Comparison of non-filtered and Savitzky-Golay filtered action potential recordings, electrical signals and corresponding optical signals. See DOI: 10.1039/c5nr01690h

A Multi-Channel, Flex-Rigid ECoG Microelectrode Array for Visual Cortical Interfacing

PubMed Central

Tolstosheeva, Elena; Gordillo-González, Víctor; Biefeld, Volker; Kempen, Ludger; Mandon, Sunita; Kreiter, Andreas K.; Lang, Walter

2015-01-01

High-density electrocortical (ECoG) microelectrode arrays are promising signal-acquisition platforms for brain-computer interfaces envisioned, e.g., as high-performance communication solutions for paralyzed persons. We propose a multi-channel microelectrode array capable of recording ECoG field potentials with high spatial resolution. The proposed array is of a 150 mm2 total recording area; it has 124 circular electrodes (100, 300 and 500 μm in diameter) situated on the edges of concentric hexagons (min. 0.8 mm interdistance) and a skull-facing reference electrode (2.5 mm2 surface area). The array is processed as a free-standing device to enable monolithic integration of a rigid interposer, designed for soldering of fine-pitch SMD-connectors on a minimal assembly area. Electrochemical characterization revealed distinct impedance spectral bands for the 100, 300 and 500 μm-type electrodes, and for the array's own reference. Epidural recordings from the primary visual cortex (V1) of an awake Rhesus macaque showed natural electrophysiological signals and clear responses to standard visual stimulation. The ECoG electrodes of larger surface area recorded signals with greater spectral power in the gamma band, while the skull-facing reference electrode provided higher average gamma power spectral density (γPSD) than the common average referencing technique. PMID:25569757

Non-clinical and Pre-clinical Testing to Demonstrate Safety of the Barostim Neo Electrode for Activation of Carotid Baroreceptors in Chronic Human Implants

PubMed Central

Wilks, Seth J.; Hara, Seth A.; Ross, Erika K.; Nicolai, Evan N.; Pignato, Paul A.; Cates, Adam W.; Ludwig, Kip A.

2017-01-01

The Barostim neo™ electrode was developed by CVRx, Inc.to deliver baroreflex activation therapy (BAT)™ to treat hypertension and heart failure. The neo electrode concept was designed to deliver electrical stimulation to the baroreceptors within the carotid sinus bulb, while minimizing invasiveness of the implant procedure. This device is currently CE marked in Europe, and in a Pivotal (akin to Phase III) Trial in the United States. Here we present the in vitro and in vivo safety testing that was completed in order to obtain necessary regulatory approval prior to conducting human studies in Europe, as well as an FDA Investigational Device Exemption (IDE) to conduct a Pivotal Trial in the United States. Stimulated electrodes (10 mA, 500 μs, 100 Hz) were compared to unstimulated electrodes using optical microscopy and several electrochemical techniques over the course of 27 weeks. Electrode dissolution was evaluated by analyzing trace metal content of solutions in which electrodes were stimulated. Lastly, safety testing under Good Laboratory Practice guidelines was conducted in an ovine animal model over a 12 and 24 week time period, with results processed and evaluated by an independent histopathologist. Long-term stimulation testing indicated that the neo electrode with a sputtered iridium oxide coating can be stimulated at maximal levels for the lifetime of the implant without clinically significant dissolution of platinum or iridium, and without increasing the potential at the electrode interface to cause hydrolysis or significant tissue damage. Histological examination of tissue that was adjacent to the neo electrodes indicated no clinically significant signs of increased inflammation and no arterial stenosis as a result of 6 months of continuous stimulation. The work presented here involved rigorous characterization and evaluation testing of the neo electrode, which was used to support its safety for chronic implantation. The testing strategies discussed provide a starting point and proven framework for testing new neuromodulation electrode concepts to support regulatory approval for clinical studies. PMID:28824361

A Device for Long-Term Perfusion, Imaging, and Electrical Interfacing of Brain Tissue In vitro

PubMed Central

Killian, Nathaniel J.; Vernekar, Varadraj N.; Potter, Steve M.; Vukasinovic, Jelena

2016-01-01

Distributed microelectrode array (MEA) recordings from consistent, viable, ≥500 μm thick tissue preparations over time periods from days to weeks may aid in studying a wide range of problems in neurobiology that require in vivo-like organotypic morphology. Existing tools for electrically interfacing with organotypic slices do not address necrosis that inevitably occurs within thick slices with limited diffusion of nutrients and gas, and limited removal of waste. We developed an integrated device that enables long-term maintenance of thick, functionally active, brain tissue models using interstitial perfusion and distributed recordings from thick sections of explanted tissue on a perforated multi-electrode array. This novel device allows for automated culturing, in situ imaging, and extracellular multi-electrode interfacing with brain slices, 3-D cell cultures, and potentially other tissue culture models. The device is economical, easy to assemble, and integrable with standard electrophysiology tools. We found that convective perfusion through the culture thickness provided a functional benefit to the preparations as firing rates were generally higher in perfused cultures compared to their respective unperfused controls. This work is a step toward the development of integrated tools for days-long experiments with more consistent, healthier, thicker, and functionally more active tissue cultures with built-in distributed electrophysiological recording and stimulation functionality. The results may be useful for the study of normal processes, pathological conditions, and drug screening strategies currently hindered by the limitations of acute (a few hours long) brain slice preparations. PMID:27065793

Complexity Optimization and High-Throughput Low-Latency Hardware Implementation of a Multi-Electrode Spike-Sorting Algorithm

PubMed Central

Dragas, Jelena; Jäckel, David; Hierlemann, Andreas; Franke, Felix

2017-01-01

Reliable real-time low-latency spike sorting with large data throughput is essential for studies of neural network dynamics and for brain-machine interfaces (BMIs), in which the stimulation of neural networks is based on the networks' most recent activity. However, the majority of existing multi-electrode spike-sorting algorithms are unsuited for processing high quantities of simultaneously recorded data. Recording from large neuronal networks using large high-density electrode sets (thousands of electrodes) imposes high demands on the data-processing hardware regarding computational complexity and data transmission bandwidth; this, in turn, entails demanding requirements in terms of chip area, memory resources and processing latency. This paper presents computational complexity optimization techniques, which facilitate the use of spike-sorting algorithms in large multi-electrode-based recording systems. The techniques are then applied to a previously published algorithm, on its own, unsuited for large electrode set recordings. Further, a real-time low-latency high-performance VLSI hardware architecture of the modified algorithm is presented, featuring a folded structure capable of processing the activity of hundreds of neurons simultaneously. The hardware is reconfigurable “on-the-fly” and adaptable to the nonstationarities of neuronal recordings. By transmitting exclusively spike time stamps and/or spike waveforms, its real-time processing offers the possibility of data bandwidth and data storage reduction. PMID:25415989

Complexity optimization and high-throughput low-latency hardware implementation of a multi-electrode spike-sorting algorithm.

PubMed

Dragas, Jelena; Jackel, David; Hierlemann, Andreas; Franke, Felix

2015-03-01

Reliable real-time low-latency spike sorting with large data throughput is essential for studies of neural network dynamics and for brain-machine interfaces (BMIs), in which the stimulation of neural networks is based on the networks' most recent activity. However, the majority of existing multi-electrode spike-sorting algorithms are unsuited for processing high quantities of simultaneously recorded data. Recording from large neuronal networks using large high-density electrode sets (thousands of electrodes) imposes high demands on the data-processing hardware regarding computational complexity and data transmission bandwidth; this, in turn, entails demanding requirements in terms of chip area, memory resources and processing latency. This paper presents computational complexity optimization techniques, which facilitate the use of spike-sorting algorithms in large multi-electrode-based recording systems. The techniques are then applied to a previously published algorithm, on its own, unsuited for large electrode set recordings. Further, a real-time low-latency high-performance VLSI hardware architecture of the modified algorithm is presented, featuring a folded structure capable of processing the activity of hundreds of neurons simultaneously. The hardware is reconfigurable “on-the-fly” and adaptable to the nonstationarities of neuronal recordings. By transmitting exclusively spike time stamps and/or spike waveforms, its real-time processing offers the possibility of data bandwidth and data storage reduction.

Optimization of return electrodes in neurostimulating arrays

NASA Astrophysics Data System (ADS)

Flores, Thomas; Goetz, Georges; Lei, Xin; Palanker, Daniel

2016-06-01

Objective. High resolution visual prostheses require dense stimulating arrays with localized inputs of individual electrodes. We study the electric field produced by multielectrode arrays in electrolyte to determine an optimal configuration of return electrodes and activation sequence. Approach. To determine the boundary conditions for computation of the electric field in electrolyte, we assessed current dynamics using an equivalent circuit of a multielectrode array with interleaved return electrodes. The electric field modeled with two different boundary conditions derived from the equivalent circuit was then compared to measurements of electric potential in electrolyte. To assess the effect of return electrode configuration on retinal stimulation, we transformed the computed electric fields into retinal response using a model of neural network-mediated stimulation. Main results. Electric currents at the capacitive electrode-electrolyte interface redistribute over time, so that boundary conditions transition from equipotential surfaces at the beginning of the pulse to uniform current density in steady state. Experimental measurements confirmed that, in steady state, the boundary condition corresponds to a uniform current density on electrode surfaces. Arrays with local return electrodes exhibit improved field confinement and can elicit stronger network-mediated retinal response compared to those with a common remote return. Connecting local return electrodes enhances the field penetration depth and allows reducing the return electrode area. Sequential activation of the pixels in large monopolar arrays reduces electrical cross-talk and improves the contrast in pattern stimulation. Significance. Accurate modeling of multielectrode arrays helps optimize the electrode configuration to maximize the spatial resolution, contrast and dynamic range of retinal prostheses.

Susceptibility of Primary Sensory Cortex to Spreading Depolarizations.

PubMed

Bogdanov, Volodymyr B; Middleton, Natalie A; Theriot, Jeremy J; Parker, Patrick D; Abdullah, Osama M; Ju, Y Sungtaek; Hartings, Jed A; Brennan, K C

2016-04-27

Spreading depolarizations (SDs) are recognized as actors in neurological disorders as diverse as migraine and traumatic brain injury (TBI). Migraine aura involves sensory percepts, suggesting that sensory cortices might be intrinsically susceptible to SDs. We used optical imaging, MRI, and field potential and potassium electrode recordings in mice and electrocorticographic recordings in humans to determine the susceptibility of different brain regions to SDs. Optical imaging experiments in mice under isoflurane anesthesia showed that both cortical spreading depression and terminal anoxic depolarization arose preferentially in the whisker barrel region of parietal sensory cortex. MRI recordings under isoflurane, ketamine/xylazine, ketamine/isoflurane, and urethane anesthesia demonstrated that the depolarizations did not propagate from a subcortical source. Potassium concentrations showed larger increases in sensory cortex, suggesting a mechanism of susceptibility. Sensory stimulation biased the timing but not the location of depolarization onset. In humans with TBI, there was a trend toward increased incidence of SDs in parietal/temporal sensory cortex compared with other regions. In conclusion, SDs are inducible preferentially in primary sensory cortex in mice and most likely in humans. This tropism can explain the predominant sensory phenomenology of migraine aura. It also demonstrates that sensory cortices are vulnerable in brain injury. Spreading depolarizations (SDs) are involved in neurologic disorders as diverse as migraine and traumatic brain injury. In migraine, the nature of aura symptoms suggests that sensory cortex may be preferentially susceptible. In brain injury, SDs occur at a vulnerable time, during which the issue of sensory stimulation is much debated. We show, in mouse and human, that sensory cortex is more susceptible to SDs. We find that sensory stimulation biases the timing but not the location of the depolarizations. Finally, we show a relative impairment of potassium clearance in sensory cortex, providing a potential mechanism for the susceptibility. Our data help to explain the sensory nature of the migraine aura and reveal that sensory cortices are vulnerable in brain injury. Copyright © 2016 the authors 0270-6474/16/364733-11$15.00/0.

Susceptibility of Primary Sensory Cortex to Spreading Depolarizations

PubMed Central

Bogdanov, Volodymyr B.; Middleton, Natalie A.; Theriot, Jeremy J.; Parker, Patrick D.; Abdullah, Osama M.; Ju, Y. Sungtaek; Hartings, Jed A.

2016-01-01

Spreading depolarizations (SDs) are recognized as actors in neurological disorders as diverse as migraine and traumatic brain injury (TBI). Migraine aura involves sensory percepts, suggesting that sensory cortices might be intrinsically susceptible to SDs. We used optical imaging, MRI, and field potential and potassium electrode recordings in mice and electrocorticographic recordings in humans to determine the susceptibility of different brain regions to SDs. Optical imaging experiments in mice under isoflurane anesthesia showed that both cortical spreading depression and terminal anoxic depolarization arose preferentially in the whisker barrel region of parietal sensory cortex. MRI recordings under isoflurane, ketamine/xylazine, ketamine/isoflurane, and urethane anesthesia demonstrated that the depolarizations did not propagate from a subcortical source. Potassium concentrations showed larger increases in sensory cortex, suggesting a mechanism of susceptibility. Sensory stimulation biased the timing but not the location of depolarization onset. In humans with TBI, there was a trend toward increased incidence of SDs in parietal/temporal sensory cortex compared with other regions. In conclusion, SDs are inducible preferentially in primary sensory cortex in mice and most likely in humans. This tropism can explain the predominant sensory phenomenology of migraine aura. It also demonstrates that sensory cortices are vulnerable in brain injury. SIGNIFICANCE STATEMENT Spreading depolarizations (SDs) are involved in neurologic disorders as diverse as migraine and traumatic brain injury. In migraine, the nature of aura symptoms suggests that sensory cortex may be preferentially susceptible. In brain injury, SDs occur at a vulnerable time, during which the issue of sensory stimulation is much debated. We show, in mouse and human, that sensory cortex is more susceptible to SDs. We find that sensory stimulation biases the timing but not the location of the depolarizations. Finally, we show a relative impairment of potassium clearance in sensory cortex, providing a potential mechanism for the susceptibility. Our data help to explain the sensory nature of the migraine aura and reveal that sensory cortices are vulnerable in brain injury. PMID:27122032

Testing assumptions on prefrontal transcranial direct current stimulation: Comparison of electrode montages using multimodal fMRI.

PubMed

Wörsching, Jana; Padberg, Frank; Goerigk, Stephan; Heinz, Irmgard; Bauer, Christine; Plewnia, Christian; Hasan, Alkomiet; Ertl-Wagner, Birgit; Keeser, Daniel

2018-05-04

Transcranial direct current stimulation (tDCS) of the prefrontal cortex (PFC) has been widely applied in cognitive neurosciences and advocated as a therapeutic intervention, e.g. in major depressive disorder. Although several targets and protocols have been suggested, comparative studies of tDCS parameters, particularly electrode montages and their cortical targets, are still lacking. This study investigated a priori hypotheses on specific effects of prefrontal-tDCS montages by using multimodal functional magnetic resonance imaging (fMRI) in healthy participants. 28 healthy male participants underwent three common active-tDCS montages and sham tDCS in a pseudo-randomized order, comprising a total of 112 tDCS-fMRI sessions. Active tDCS was applied at 2 mA for 20 min. Before and after tDCS, a resting-state fMRI (RS fMRI) was recorded, followed by a task fMRI with a delayed-response working-memory (DWM) task for assessing cognitive control over emotionally negative or neutral distractors. After tDCS with a cathode-F3/anode-F4 montage, RS-fMRI connectivity decreased in a medial part of the left PFC. Also, after the same stimulation condition, regional brain activity during DWM retrieval decreased more in this area after negative than after neutral distraction, and responses to the DWM task were faster, independent of distractor type. The current study does not confirm our a priori hypotheses on direction and localization of polarity-dependent tDCS effects using common bipolar electrode montages over PFC regions, but it provides evidence for montage-specific effects on multimodal neurophysiological and behavioral outcome measures. Systematic research on the actual targets and the respective dose-response relationships of prefrontal tDCS is warranted. Copyright © 2018 Elsevier Inc. All rights reserved.

Evaluation of focused multipolar stimulation for cochlear implants in long-term deafened cats

NASA Astrophysics Data System (ADS)

George, Shefin S.; Wise, Andrew K.; Fallon, James B.; Shepherd, Robert K.

2015-06-01

Objective. Focused multipolar (FMP) stimulation has been shown to produce restricted neural activation using intracochlear stimulation in animals with a normal population of spiral ganglion neurons (SGNs). However, in a clinical setting, the widespread loss of SGNs and peripheral fibres following deafness is expected to influence the effectiveness of FMP. Approach. We compared the efficacy of FMP stimulation to both monopolar (MP) and tripolar (TP) stimulation in long-term deafened cat cochleae (n = 8). Unlike our previous study, these cochleae contained <10% of the normal SGN population adjacent to the electrode array. We also evaluated the effect of electrode position on stimulation modes by using either modiolar facing or lateral wall facing half-band electrodes. The spread of neural activity across the inferior colliculus, a major nucleus within the central auditory pathway, was used as a measure of spatial selectivity. Main results. In cochleae with significant SGN degeneration, we observed that FMP and TP stimulation resulted in greater spatial selectivity than MP stimulation (p < 0.001). However, thresholds were significantly higher for FMP and TP stimulation compared to MP stimulation (p < 0.001). No difference between FMP and TP stimulation was found in any measures. The high threshold levels for FMP stimulation was significantly reduced without compromising spatial selectivity by varying the degree of current focusing (referred as ‘partial-FMP’ stimulation). Spatial selectivity of all stimulation modes was unaffected by the electrode position. Finally, spatial selectivity in long-term deafened cochleae was significantly less than that of cochleae with normal SGN population (George S S et al 2014 J. Neural Eng. 11 065003). Significance. The present results indicate that the greater spatial selectivity of FMP and TP stimulation over MP stimulation is maintained in cochleae with significant neural degeneration and is not adversely affected by electrode position. The greater spatial selectivity of FMP and TP stimulation would be expected to result in improved clinical performance.

Computational modeling of epidural cortical stimulation

NASA Astrophysics Data System (ADS)

Wongsarnpigoon, Amorn; Grill, Warren M.

2008-12-01

Epidural cortical stimulation (ECS) is a developing therapy to treat neurological disorders. However, it is not clear how the cortical anatomy or the polarity and position of the electrode affects current flow and neural activation in the cortex. We developed a 3D computational model simulating ECS over the precentral gyrus. With the electrode placed directly above the gyrus, about half of the stimulus current flowed through the crown of the gyrus while current density was low along the banks deep in the sulci. Beneath the electrode, neurons oriented perpendicular to the cortical surface were depolarized by anodic stimulation, and neurons oriented parallel to the boundary were depolarized by cathodic stimulation. Activation was localized to the crown of the gyrus, and neurons on the banks deep in the sulci were not polarized. During regulated voltage stimulation, the magnitude of the activating function was inversely proportional to the thickness of the CSF and dura. During regulated current stimulation, the activating function was not sensitive to the thickness of the dura but was slightly more sensitive than during regulated voltage stimulation to the thickness of the CSF. Varying the width of the gyrus and the position of the electrode altered the distribution of the activating function due to changes in the orientation of the neurons beneath the electrode. Bipolar stimulation, although often used in clinical practice, reduced spatial selectivity as well as selectivity for neuron orientation.

The Impact of Subthalamic Deep Brain Stimulation on Sleep-Wake Behavior: A Prospective Electrophysiological Study in 50 Parkinson Patients.

PubMed

Baumann-Vogel, Heide; Imbach, Lukas L; Sürücü, Oguzkan; Stieglitz, Lennart; Waldvogel, Daniel; Baumann, Christian R; Werth, Esther

2017-05-01

This prospective observational study was designed to systematically examine the effect of subthalamic deep brain stimulation (DBS) on subjective and objective sleep-wake parameters in Parkinson patients. In 50 consecutive Parkinson patients undergoing subthalamic DBS, we assessed motor symptoms, medication, the position of DBS electrodes within the subthalamic nucleus (STN), subjective sleep-wake parameters, 2-week actigraphy, video-polysomnography studies, and sleep electroencepahalogram frequency and dynamics analyses before and 6 months after surgery. Subthalamic DBS improved not only motor symptoms and reduced daily intake of dopaminergic agents but also enhanced subjective sleep quality and reduced sleepiness (Epworth Sleepiness Scale: -2.1 ± 3.8, p < .001). Actigraphy recordings revealed longer bedtimes (+1:06 ± 0:51 hours, p < .001) without shifting of circadian timing. Upon polysomnography, we observed an increase in sleep efficiency (+5.2 ± 17.6%, p = .005) and deep sleep (+11.2 ± 32.2 min, p = .017) and increased accumulation of slow-wave activity over the night (+41.0 ± 80.0%, p = .005). Rapid eye movement sleep features were refractory to subthalamic DBS, and the dynamics of sleep as assessed by state space analyses did not normalize. Increased sleep efficiency was associated with active electrode contact localization more distant from the ventral margin of the left subthalamic nucleus. Subthalamic DBS deepens and consolidates nocturnal sleep and improves daytime wakefulness in Parkinson patients, but several outcomes suggest that it does not normalize sleep. It remains elusive whether modulated activity in the STN directly contributes to changes in sleep-wake behavior, but dorsal positioning of electrodes within the STN is linked to improved sleep-wake outcomes. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

The Electrically Evoked Auditory Change Complex Evoked by Temporal Gaps Using Cochlear Implants or Auditory Brainstem Implants in Children With Cochlear Nerve Deficiency.

PubMed

He, Shuman; McFayden, Tyler C; Shahsavarani, Bahar S; Teagle, Holly F B; Ewend, Matthew; Henderson, Lillian; Buchman, Craig A

This study aimed to (1) establish the feasibility of measuring the electrically evoked auditory change complex (eACC) in response to temporal gaps in children with cochlear nerve deficiency (CND) who are using cochlear implants (CIs) and/or auditory brainstem implants (ABIs); and (2) explore the association between neural encoding of, and perceptual sensitivity to, temporal gaps in these patients. Study participants included 5 children (S1 to S5) ranging in age from 3.8 to 8.2 years (mean: 6.3 years) at the time of testing. All subjects were unilaterally implanted with a Nucleus 24M ABI due to CND. For each subject, two or more stimulating electrodes of the ABI were tested. S2, S3, and S5 previously received a CI in the contralateral ear. For these 3 subjects, at least two stimulating electrodes of their CIs were also tested. For electrophysiological measures, the stimulus was an 800-msec biphasic pulse train delivered to individual electrodes at the maximum comfortable level (C level). The electrically evoked responses, including the onset response and the eACC, were measured for two stimulation conditions. In the standard condition, the 800-msec pulse train was delivered uninterrupted to individual stimulating electrodes. In the gapped condition, a temporal gap was inserted into the pulse train after 400 msec of stimulation. Gap durations tested in this study ranged from 2 up to 128 msec. The shortest gap that could reliably evoke the eACC was defined as the objective gap detection threshold (GDT). For behavioral GDT measures, the stimulus was a 500-msec biphasic pulse train presented at the C level. The behavioral GDT was measured for individual stimulating electrodes using a one-interval, two-alternative forced-choice procedure. The eACCs to temporal gaps were recorded successfully in all subjects for at least one stimulating electrode using either the ABI or the CI. Objective GDTs showed intersubject variations, as well as variations across stimulating electrodes of the ABI or the CI within each subject. Behavioral GDTs were measured for one ABI electrode in S2 and for multiple ABI and CI electrodes in S5. All other subjects could not complete the task. S5 showed smaller behavioral GDTs for CI electrodes than those measured for ABI electrodes. One CI and two ABI electrodes in S5 showed comparable objective and behavioral GDTs. In contrast, one CI and two ABI electrodes in S5 and one ABI electrode in S2 showed measurable behavioral GDTs but no identifiable eACCs. The eACCs to temporal gaps were recorded in children with CND using either ABIs or CIs. Both objective and behavioral GDTs showed inter- and intrasubject variations. Consistency between results of eACC recordings and psychophysical measures of GDT was observed for some but not all ABI or CI electrodes in these subjects.

Development of the Mayo Investigational Neuromodulation Control System: toward a closed-loop electrochemical feedback system for deep brain stimulation

PubMed Central

Chang, Su-Youne; Kimble, Christopher J.; Kim, Inyong; Paek, Seungleal B.; Kressin, Kenneth R.; Boesche, Joshua B.; Whitlock, Sidney V.; Eaker, Diane R.; Kasasbeh, Aimen; Horne, April E.; Blaha, Charles D.; Bennet, Kevin E.; Lee, Kendall H.

2014-01-01

Object Conventional deep brain stimulation (DBS) devices continue to rely on an open-loop system in which stimulation is independent of functional neural feedback. The authors previously proposed that as the foundation of a DBS “smart” device, a closed-loop system based on neurochemical feedback, may have the potential to improve therapeutic outcomes. Alterations in neurochemical release are thought to be linked to the clinical benefit of DBS, and fast-scan cyclic voltammetry (FSCV) has been shown to be effective for recording these evoked neurochemical changes. However, the combination of FSCV with conventional DBS devices interferes with the recording and identification of the evoked analytes. To integrate neurochemical recording with neurostimulation, the authors developed the Mayo Investigational Neuromodulation Control System (MINCS), a novel, wirelessly controlled stimulation device designed to interface with FSCV performed by their previously described Wireless Instantaneous Neurochemical Concentration Sensing System (WINCS). Methods To test the functionality of these integrated devices, various frequencies of electrical stimulation were applied by MINCS to the medial forebrain bundle of the anesthetized rat, and striatal dopamine release was recorded by WINCS. The parameters for FSCV in the present study consisted of a pyramidal voltage waveform applied to the carbon-fiber microelectrode every 100 msec, ramping between −0.4 V and +1.5 V with respect to an Ag/AgCl reference electrode at a scan rate of either 400 V/sec or 1000 V/sec. The carbon-fiber microelectrode was held at the baseline potential of −0.4 V between scans. Results By using MINCS in conjunction with WINCS coordinated through an optic fiber, the authors interleaved intervals of electrical stimulation with FSCV scans and thus obtained artifact-free wireless FSCV recordings. Electrical stimulation of the medial forebrain bundle in the anesthetized rat by MINCS elicited striatal dopamine release that was time-locked to stimulation and increased progressively with stimulation frequency. Conclusions Here, the authors report a series of proof-of-principle tests in the rat brain demonstrating MINCS to be a reliable and flexible stimulation device that, when used in conjunction with WINCS, performs wirelessly controlled stimulation concurrent with artifact-free neurochemical recording. These findings suggest that the integration of neurochemical recording with neurostimulation may be a useful first step toward the development of a closed-loop DBS system for human application. PMID:24116724

Stimulation of the pedunculopontine nucleus area in Parkinson's disease: effects on speech and intelligibility.

PubMed

Pinto, Serge; Ferraye, Murielle; Espesser, Robert; Fraix, Valérie; Maillet, Audrey; Guirchoum, Jennifer; Layani-Zemour, Deborah; Ghio, Alain; Chabardès, Stéphan; Pollak, Pierre; Debû, Bettina

2014-10-01

Improvement of gait disorders following pedunculopontine nucleus area stimulation in patients with Parkinson's disease has previously been reported and led us to propose this surgical treatment to patients who progressively developed severe gait disorders and freezing despite optimal dopaminergic drug treatment and subthalamic nucleus stimulation. The outcome of our prospective study on the first six patients was somewhat mitigated, as freezing of gait and falls related to freezing were improved by low frequency electrical stimulation of the pedunculopontine nucleus area in some, but not all, patients. Here, we report the speech data prospectively collected in these patients with Parkinson's disease. Indeed, because subthalamic nucleus surgery may lead to speech impairment and a worsening of dysarthria in some patients with Parkinson's disease, we felt it was important to precisely examine any possible modulations of speech for a novel target for deep brain stimulation. Our results suggested a trend towards speech degradation related to the pedunculopontine nucleus area surgery (off stimulation) for aero-phonatory control (maximum phonation time), phono-articulatory coordination (oral diadochokinesis) and speech intelligibility. Possibly, the observed speech degradation may also be linked to the clinical characteristics of the group of patients. The influence of pedunculopontine nucleus area stimulation per se was more complex, depending on the nature of the task: it had a deleterious effect on maximum phonation time and oral diadochokinesis, and mixed effects on speech intelligibility. Whereas levodopa intake and subthalamic nucleus stimulation alone had no and positive effects on speech dimensions, respectively, a negative interaction between the two treatments was observed both before and after pedunculopontine nucleus area surgery. This combination effect did not seem to be modulated by pedunculopontine nucleus area stimulation. Although limited in our group of patients, speech impairment following pedunculopontine nucleus area stimulation is a possible outcome that should be considered before undertaking such surgery. Deleterious effects could be dependent on electrode insertion in this brainstem structure, more than on current spread to nearby structures involved in speech control. The effect of deep brain stimulation on speech in patients with Parkinson's disease remains a challenging and exploratory research area. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Optimal control of directional deep brain stimulation in the parkinsonian neuronal network

NASA Astrophysics Data System (ADS)

Fan, Denggui; Wang, Zhihui; Wang, Qingyun

2016-07-01

The effect of conventional deep brain stimulation (DBS) on debilitating symptoms of Parkinson's disease can be limited because it can only yield the spherical field. And, some side effects are clearly induced with influencing their adjacent ganglia. Recent experimental evidence for patients with Parkinson's disease has shown that a novel DBS electrode with 32 independent stimulation source contacts can effectively optimize the clinical therapy by enlarging the therapeutic windows, when it is applied on the subthalamic nucleus (STN). This is due to the selective activation in clusters of various stimulation contacts which can be steered directionally and accurately on the targeted regions of interest. In addition, because of the serious damage to the neural tissues, the charge-unbalanced stimulation is not typically indicated and the real DBS utilizes charge-balanced bi-phasic (CBBP) pulses. Inspired by this, we computationally investigate the optimal control of directional CBBP-DBS from the proposed parkinsonian neuronal network of basal ganglia-thalamocortical circuit. By appropriately tuning stimulation for different neuronal populations, it can be found that directional steering CBBP-DBS paradigms are superior to the spherical case in improving parkinsonian dynamical properties including the synchronization of neuronal populations and the reliability of thalamus relaying the information from cortex, which is in a good agreement with the physiological experiments. Furthermore, it can be found that directional steering stimulations can increase the optimal stimulation intensity of desynchronization by more than 1 mA compared to the spherical case. This is consistent with the experimental result with showing that there exists at least one steering direction that can allow increasing the threshold of side effects by 1 mA. In addition, we also simulate the local field potential (LFP) and dominant frequency (DF) of the STN neuronal population induced by the activation of 32 different contacts with optimal stimulation intensity and immediately after the stimulation, respectively. These can reveal regional differences in pathological activity within STN nucleus. It is shown that in line with the experimental results directional steering stimulation can induce the low-amplitude LFP which implies the occurrence of desynchronizing regime, as well as the distribution of DF can locate at the 13-40 Hz of beta frequency range. Hopefully, the obtained results can provide theoretical evidences in exploring pathophysiologic activity of brain.

Demultiplexer circuit for neural stimulation

DOEpatents

Wessendorf, Kurt O; Okandan, Murat; Pearson, Sean

2012-10-09

A demultiplexer circuit is disclosed which can be used with a conventional neural stimulator to extend the number of electrodes which can be activated. The demultiplexer circuit, which is formed on a semiconductor substrate containing a power supply that provides all the dc electrical power for operation of the circuit, includes digital latches that receive and store addressing information from the neural stimulator one bit at a time. This addressing information is used to program one or more 1:2.sup.N demultiplexers in the demultiplexer circuit which then route neural stimulation signals from the neural stimulator to an electrode array which is connected to the outputs of the 1:2.sup.N demultiplexer. The demultiplexer circuit allows the number of individual electrodes in the electrode array to be increased by a factor of 2.sup.N with N generally being in a range of 2-4.