Brain-Controlled Muscle Stimulation for the Restoration of Motor Function

Total Page:16

File Type:pdf, Size:1020Kb

Brain-Controlled Muscle Stimulation for the Restoration of Motor Function Neurobiology of Disease 83 (2015) 180–190 Contents lists available at ScienceDirect Neurobiology of Disease journal homepage: www.elsevier.com/locate/ynbdi Review Brain-controlled muscle stimulation for the restoration of motor function Christian Ethier a, Lee E. Miller a,b,c,⁎ a Department of Physiology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Ave., Chicago, IL 60611, USA b Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road Evanston, IL 60208, USA c Department of Physical Medicine and Rehabilitation, Feinberg School of Medicine, Northwestern University, 345 E. Superior Ave., Chicago, IL 60611,USA article info abstract Article history: Loss of the ability to move, as a consequence of spinal cord injury or neuromuscular disorder, has devastating Received 17 May 2014 consequences for the paralyzed individual, and great economic consequences for society. Functional electrical Revised 14 October 2014 stimulation (FES) offers one means to restore some mobility to these individuals, improving not only their auton- Accepted 20 October 2014 omy, but potentially their general health and well-being as well. FES uses electrical stimulation to cause the par- Available online 28 October 2014 alyzed muscles to contract. Existing clinical systems require the stimulation to be preprogrammed, with the patient typically using residual voluntary movement of another body part to trigger and control the patterned Keywords: Functional electrical stimulation stimulation. The rapid development of neural interfacing in the past decade offers the promise of dramatically Spinal cord injury improved control for these patients, potentially allowing continuous control of FES through signals recorded Paralysis from motor cortex, as the patient attempts to control the paralyzed body part. While application of Brain–machine interface these ‘brain–machine interfaces’ (BMIs) has undergone dramatic development for control of computer cursors Motor cortex and even robotic limbs, their use as an interface for FES has been much more limited. In this review, we consider both FES and BMI technologies and discuss the prospect for combining the two to provide important new options for paralyzed individuals. © 2014 Elsevier Inc. All rights reserved. Contents 1. Introduction.............................................................. 181 2. FESsystems.............................................................. 181 2.1. MuscleactivationbyFES..................................................... 181 2.2. FESforlowerlimbfunction.................................................... 182 2.3. FESforupperlimbfunction.................................................... 183 3. Decodingmotorintentfromthebrain................................................... 183 3.1. ScalpEEGasabraininterface................................................... 183 3.2. Fieldrecordingusingelectrodegridsimplantedonthesurfaceofthebrain............................... 184 3.3. Intracorticalrecordingofneuronalactionpotentials......................................... 184 4. Approachestobrain-controlledFES.................................................... 184 5. Brain-controlledmusclestimulationforthereplacementoffunction...................................... 185 5.1. Restorationofgrasping...................................................... 185 5.2. Restorationoflowerlimbfunction................................................. 186 5.3. Remainingchallengesforbrain-controlledFES............................................ 186 6. Conclusions............................................................... 187 Acknowledgments.............................................................. 187 References.................................................................. 187 ⁎ Corresponding author at: Department of Physiology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Ave., Chicago, IL 60611, USA. Fax: +1 312 503 5101. E-mail address: [email protected] (L.E. Miller). Available online on ScienceDirect (www.sciencedirect.com). http://dx.doi.org/10.1016/j.nbd.2014.10.014 0969-9961/© 2014 Elsevier Inc. All rights reserved. C. Ethier, L.E. Miller / Neurobiology of Disease 83 (2015) 180–190 181 1. Introduction cord injury, stroke, multiple sclerosis, or cerebral palsy. In addition to the replacement of motor function that is its most obvious benefit, FES Paralysis resulting from spinal cord injury (SCI), cortical lesion or neuro- can have more general benefit as well. FES improves the contractile muscular disease is devastating, dramatically reducing the range of activi- force of the remaining motor units to which the patient has voluntary ties of daily living (ADL) and quality of life of patients. In addition to the access (Baldi et al., 1998; Powell et al., 1999), as would traditional direct effects, a number of secondary complications emerge as a result of muscular training. It also may improve the range of motion of the affect- disuse, such as muscle atrophy, contractures and pressure sores (Baldi ed limb beyond that of passive physical therapy (Kraft et al., 1992; et al., 1998; Ragnarsson, 2008). Among those patients with tetraplegia, Pandyan et al., 1997), particularly for less severely affected patients the great majority identify the return of hand function as their most critical (Powell et al., 1999; Sonde et al., 1998; von Lewinski et al., 2009). FES need (Anderson, 2004; French et al., 2010). Those patients with loss only of may also reduce spasticity and contractures, though this remains un- lower limb function list a number of different priorities. If the motoneurons clear (Alfieri, 2001; Malhotra et al., 2012). In addition, there are indirect remain intact after injury, muscles can still be made to contract through the effects that result from contracting paralyzed muscles: activation of the application of electric currents to the nerve or neuromuscular junction, a cardiopulmonary system, strengthening of bones, and relief of pressure procedure referred to as functionalelectricalstimulation(FES)(Peckham sores. Finally, the neuronal activity generated by FES may lead to and Knutson, 2005; Ragnarsson, 2008). In the past several decades, impor- activity-dependent plastic changes in the nervous system. These effects tant progress has been made using FES to assist or restore motor function in can be difficult to evaluate in light of the changes in the periphery. How- patients, enabling them to improve their gait (Daly et al., 2011; Granat et al., ever, FES has been shown to contribute to neurogenesis (Liuetal., 1993; Thrasher et al., 2005), grasp objects (Alon and McBride, 2003; 2013a), axonal growth (Al-Majed et al., 2004; Liu et al., 2013b), sensory Peckham et al., 1980, 2001; Popovic et al., 2002), and to augment bowel neuron regeneration (Geremia et al., 2007), and to promote recovery of and bladder function (Gaunt and Prochazka, 2006). FES systems can be of spinal reflexes (Knikou and Conway, 2005; Lynskey et al., 2008). great benefit to paralyzed patients, by providing an increase in autonomy Popovic et al. listed three requirements that need to be fulfilled in through improvements in their activities of daily living. order to include FES as a rehabilitation tool (Popovic et al., 2001). A variety of control sources have been used to command FES. Foot First, the muscles that are intended for FES need to be accessible for drop correction can be controlled by a simple switch activated by electrode placement. Surface electrodes have few contraindications sensors near the heel of the foot, by sensing acceleration or by signals aside from the pain they may cause if sensation is intact, but they cannot recorded from the peroneal nerve (Pappas et al., 2001; Popovic et al., activate deeper muscles well. Percutaneous or implanted electrodes are 1993; Rueterbories et al., 2010; Skelly and Chizeck, 2001; Tong and more selective, but are more invasive and may not be indicated for some Granat, 1999; Williamson and Andrews, 2000). Likewise, switches can patients, particularly in the early stages after injury. be used to activate pre-programmed stimulation patterns for grasp, Second, there should not be a major degree of motoneuron or nerve and to initiate sit-to-stand movements (Gallien et al., 1995; Graupe root damage of the stimulated muscle. Intramuscular stimulation et al., 1998; Graupe and Kohn, 1998). More finely-graded control can normally activates muscles indirectly, by first evoking action potentials be achieved by joint angle sensors or measurement of residual muscle in the nerve terminals. SCI patients often have some level of motoneuro- activity. However, these control modes are limited in bandwidth, and nal damage around the level of injury, which may restrict the use of FES are initially unnatural and unintuitive for patients. Furthermore, with for some muscles. Activation of denervated muscles is possible with increasingly high level SCI, the patients have at once greater need for much higher current, but is not very effective as a means to recruit replaced function and fewer available control options. muscles in a selective and functionally useful manner (Kern et al., The advances made in the field of brain–machine interfaces over the 2002; Mayr et al., 2002). past 10 years provide the possibility to extract a user's own movement Third, Popovic et al. noted that for FES to be useful, the voluntary intent directly from the brain. The majority of these applications function of the more proximal limb muscles must
Recommended publications
  • Neural Dust: Ultrasonic Biological Interface
    Neural Dust: Ultrasonic Biological Interface Dongjin (DJ) Seo Electrical Engineering and Computer Sciences University of California at Berkeley Technical Report No. UCB/EECS-2018-146 http://www2.eecs.berkeley.edu/Pubs/TechRpts/2018/EECS-2018-146.html December 1, 2018 Copyright © 2018, by the author(s). All rights reserved. Permission to make digital or hard copies of all or part of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for profit or commercial advantage and that copies bear this notice and the full citation on the first page. To copy otherwise, to republish, to post on servers or to redistribute to lists, requires prior specific permission. Neural Dust: Ultrasonic Biological Interface by Dongjin Seo A dissertation submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Engineering - Electrical Engineering and Computer Sciences in the Graduate Division of the University of California, Berkeley Committee in charge: Professor Michel M. Maharbiz, Chair Professor Elad Alon Professor John Ngai Fall 2016 Neural Dust: Ultrasonic Biological Interface Copyright 2016 by Dongjin Seo 1 Abstract Neural Dust: Ultrasonic Biological Interface by Dongjin Seo Doctor of Philosophy in Engineering - Electrical Engineering and Computer Sciences University of California, Berkeley Professor Michel M. Maharbiz, Chair A seamless, high density, chronic interface to the nervous system is essential to enable clinically relevant applications such as electroceuticals or brain-machine interfaces (BMI). Currently, a major hurdle in neurotechnology is the lack of an implantable neural interface system that remains viable for a patient's lifetime due to the development of biological response near the implant.
    [Show full text]
  • Perceiving Invisible Light Through a Somatosensory Cortical Prosthesis
    ARTICLE Received 24 Aug 2012 | Accepted 15 Jan 2013 | Published 12 Feb 2013 DOI: 10.1038/ncomms2497 Perceiving invisible light through a somatosensory cortical prosthesis Eric E. Thomson1,2, Rafael Carra1,w & Miguel A.L. Nicolelis1,2,3,4,5 Sensory neuroprostheses show great potential for alleviating major sensory deficits. It is not known, however, whether such devices can augment the subject’s normal perceptual range. Here we show that adult rats can learn to perceive otherwise invisible infrared light through a neuroprosthesis that couples the output of a head-mounted infrared sensor to their soma- tosensory cortex (S1) via intracortical microstimulation. Rats readily learn to use this new information source, and generate active exploratory strategies to discriminate among infrared signals in their environment. S1 neurons in these infrared-perceiving rats respond to both whisker deflection and intracortical microstimulation, suggesting that the infrared repre- sentation does not displace the original tactile representation. Hence, sensory cortical prostheses, in addition to restoring normal neurological functions, may serve to expand natural perceptual capabilities in mammals. 1 Department of Neurobiology, Duke University, Box 3209, 311 Research Drive, Bryan Research, Durham, North Carolina 27710, USA. 2 Edmond and Lily Safra International Institute for Neuroscience of Natal (ELS-IINN), Natal 01257050, Brazil. 3 Department of Biomedical Engineering, Duke University, Durham, North Carolina 27710, USA. 4 Department of Psychology and Neuroscience, Duke University, Durham, North Carolina 27710, USA. 5 Center for Neuroengineering, Duke University, Durham, North Carolina 27710, USA. w Present address: University of Sao Paulo School of Medicine, Sao Paulo 01246-000, Brazil. Correspondence and requests for materials should be addressed to M.A.L.N.
    [Show full text]
  • Optogenetics Controlling Neurons with Photons
    Valerie C. Coffey Optogenetics Controlling Neurons with Photons An advancing field of neuroscience uses light to understand how the brain works and to create new tools to treat disease. Wireless optogenetics tools like these tiny implants in live mice are enabling scientists to map the stimulation of certain neurons of the brain to specific responses. J. Rogers/Northwestern Univ. 24 OPTICS & PHOTONICS NEWS APRIL 2018 APRIL 2018 OPTICS & PHOTONICS NEWS 25 In just over a decade, the discovery of numerous opsins with different specializations has allowed scientists and engineers to make rapid progress in mapping brain activity. wo thousand years ago, ancient Egyptians halorhodopsin can silence the neurons in the hypo- knew that the electrical shocks of torpedo thalamus, inducing sleep in living mice. fish, applied to the body, could offer pain In just over a decade, the discovery of numerous relief. Two hundred years ago, physicians opsins with different specializations has allowed scien- understood that electrical stimulation of a tists and engineers to make rapid progress in mapping Tfrog’s spine could control muscle contraction. Today, brain activity, motivated by the hope of solving intrac- electrical therapy underlies many treatments, from table neurological conditions. And it doesn’t hurt that pacemakers to pain control. investment in neuroscience research has grown at the But neuroscience has long awaited a more precise same time. tool for controlling specific types of neurons. Electrical In 2013, the Obama administration announced a stimulation (e-stim) approaches stimulate a large area collaborative public-private effort, the Brain Research without precise spatial control, and can’t distinguish through Advancing Innovative Neurotechnologies between different cell types.
    [Show full text]
  • Computational Neuroscience Meets Optogenetics: Unlocking the Brain’S Secrets
    Health & Medicine ︱ Prof Simon Schultz and Dr Konstantin Nikolic Computational neuroscience meets optogenetics: Unlocking the brain’s secrets Working at the interface omposed of billions of specialised responsible for perception, action Simplified models allow researchers to study how the geometry of a neuron’s “dendritic tree” affects its ability to process information. between engineering and nerve cells (called neurons) wired and memory. But this is changing. neuroscience, Professor Simon C together in complex, intricate Schultz and Dr Konstantin webs, the brain is inherently challenging LET THERE BE LIGHT Nikolic at Imperial College to study. Neurons communicate with A powerful new tool (invented by Boyden of Neurotechnology and Director of SHEDDING LIGHT ON THE BRAIN AN INSIGHT INTO NEURONAL GAIN London are developing tools each other by transmitting electrical and and Deisseroth just a little over a decade the Imperial Centre of Excellence in Their innovative approach uses Using two biophysical models of to help us understand the chemical signals along neural circuits: ago) allows researchers to map the brain’s Neurotechnology, Dr Konstantin Nikolic, sophisticated two-photon microscopy, neurons, genetically-modified to include intricate workings of the brain. signals that vary both in space and time. connections, giving unprecedented Associate Professor in the Department optogenetics and electrophysiology two distinct light-sensitive proteins Combining a revolutionary Until now, technical limitations in the access to the workings of the brain. Its of Electrical and Electronic Engineering, to measure (and disturb) patterns of (called opsins): channelrhodopsin-2 technology – optogenetics available research methods to study the impressive resolution enables precise and Dr Sarah Jarvis are taking a unique neuronal activity in vivo (in living tissue).
    [Show full text]
  • Mousecircuits.Org: an Online Repository to Guide the Circuit Era of Disordered Affect
    bioRxiv preprint doi: https://doi.org/10.1101/2020.02.16.951608; this version posted February 17, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. MouseCircuits.org: An online repository to guide the circuit era of disordered affect Kristin R. Anderson ID 1,2 and Dani Dumitriu ID 1,2 1Columbia University, Departments of Pediatrics and Psychiatry, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032 2Columbia University, Zuckerman Institute, 3227 Broadway, New York, NY 10027 Affective disorders rank amongst the most disruptive and tem and the gut microbiome (2,3). However, the mysteries of prevalent psychiatric diseases, resulting in enormous societal the brain, a structure with idiosyncratic and interconnected and economic burden, and immeasurable personal costs. Novel architecture, are unlikely to be revealed solely on the basis of therapies are urgently needed but have remained elusive. The this type of sledgehammer approach. era of circuit-mapping in rodent models of disordered affect, ushered in by recent technological advancements allowing for Enter the era of circuit dissection. In the last precise and specific neural control, has reenergized the hope for decade, groundbreaking technological advances have al- precision psychiatry. Here, we present a novel whole-brain cu- lowed neuroscientists to take control of neural firing with mulative network and critically access the progress made to- impressive precision and specificity (Figure 1) (4–7).
    [Show full text]
  • An Embedded Real-Time Processing Platform for Optogenetic Neuroprosthetic Applications
    IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING, VOL. 26, NO. 1, JANUARY 2018 233 An Embedded Real-Time Processing Platform for Optogenetic Neuroprosthetic Applications Boyuan Yan and Sheila Nirenberg Abstract— Optogenetics offers a powerful new approach temporal resolution. Since these proteins require bright for controlling neural circuits. It has numerous applica- light [23], [24], standard high resolution devices such as LCD tions in both basic and clinical science. These applications monitors are ineffective. While laser or LED-based illumi- require stimulating devices with small processors that can perform real-time neural signal processing, deliver high- nation systems can meet the requirements of light intensity, intensity light with high spatial and temporal resolution, they are not readily suitable for providing spatially-patterned and do not consume a lot of power. In this paper, we stimuli. Digital light processing (DLP) projectors, however demonstrate the implementation of neuronal models in a can achieve this: the key component, a chip called Digital platform consisting of an embedded system module and Micromirror Device (DMD) [25], consists of an array of a portable digital light processing projector. As a replace- ment for damaged neural circuitry, the embedded module several hundred thousand micromirrors, which can change processes neural signals and then directs the projector to position at kHz frequencies. These offer the most flexibility in optogenetically activate a downstream neural pathway. We terms of the spatial and temporal modulation of the activating present a design in the context of stimulating circuits in the light. visual system, but the approach is feasible for a broad range In addition to an effective stimulator, the other essential of biomedical applications.
    [Show full text]
  • Implantable Microelectrodes on Soft Substrate with Nanostructured Active Surface for Stimulation and Recording of Brain Activities Valentina Castagnola
    Implantable microelectrodes on soft substrate with nanostructured active surface for stimulation and recording of brain activities Valentina Castagnola To cite this version: Valentina Castagnola. Implantable microelectrodes on soft substrate with nanostructured active sur- face for stimulation and recording of brain activities. Micro and nanotechnologies/Microelectronics. Universite Toulouse III Paul Sabatier, 2014. English. tel-01137352 HAL Id: tel-01137352 https://hal.archives-ouvertes.fr/tel-01137352 Submitted on 31 Mar 2015 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. THÈSETHÈSE En vue de l’obtention du DOCTORAT DE L’UNIVERSITÉ DE TOULOUSE Délivré par : l’Université Toulouse 3 Paul Sabatier (UT3 Paul Sabatier) Présentée et soutenue le 18/12/2014 par : Valentina CASTAGNOLA Implantable Microelectrodes on Soft Substrate with Nanostructured Active Surface for Stimulation and Recording of Brain Activities JURY M. Frédéric MORANCHO Professeur d’Université Président de jury M. Blaise YVERT Directeur de recherche Rapporteur Mme Yael HANEIN Professeur d’Université Rapporteur M. Pascal MAILLEY Directeur de recherche Examinateur M. Christian BERGAUD Directeur de recherche Directeur de thèse Mme Emeline DESCAMPS Chargée de Recherche Directeur de thèse École doctorale et spécialité : GEET : Micro et Nanosystèmes Unité de Recherche : Laboratoire d’Analyse et d’Architecture des Systèmes (UPR 8001) Directeur(s) de Thèse : M.
    [Show full text]
  • Neuroprosthetics Session Abstract-FINAL
    NEUROPROTHETICS Session co-chairs: Justin Williams, University of Wisconsin, Tim Denison, Medtronic The brain has always been attractive to engineers. Neurons and their connections, like tiny circuit elements, process and transmit information in a dramatic way that is intimately curious to researchers in the computer science and engineering fields. Neurons are amazing computational devices capable of both robust response to widely varied inputs and adaptability to changing conditions. Our most advanced computing systems are still dwarfed by the computational power of the human brain. Even small groups of neurons are capable of intricate interactions that produce basic mechanisms of learning and memory, highly parallel processing and exquisite sensing capabilities. Science has made great strides in the past few decades toward uncovering the basic principles underlying the brain’s ability to receive sensation and control movement. These discoveries, along with revolutionary advances in computing power and microelectronics technology, have led to an emerging view that neural prosthetics, or electronic interfaces with the brain for restoration or augmentation of physiological function, may one day be possible. While the creation of a “six million dollar man" may still be far into the future, neural prostheses are rapidly becoming real potential treatments for a broad range of patients with injury or disease of the nervous system. This session will focus on the types of engineering technology that we use to interface with the nervous system. This includes technology for stimulating the nervous system for restoration of sensory function as well as methods for extracting motor intention from the brain for use in artificial prostheses.
    [Show full text]
  • Optogenetics Inspired Transition Metal Dichalcogenide Neuristors for In-Memory Deep Recurrent Neural Networks
    ARTICLE https://doi.org/10.1038/s41467-020-16985-0 OPEN Optogenetics inspired transition metal dichalcogenide neuristors for in-memory deep recurrent neural networks Rohit Abraham John 1, Jyotibdha Acharya2,3, Chao Zhu 1, Abhijith Surendran2, Sumon Kumar Bose 2, Apoorva Chaturvedi1, Nidhi Tiwari4, Yang Gao1, Yongmin He 1, Keke K. Zhang1, Manzhang Xu 1, ✉ ✉ Wei Lin Leong 2, Zheng Liu 1, Arindam Basu 2 & Nripan Mathews 1,4 1234567890():,; Shallow feed-forward networks are incapable of addressing complex tasks such as natural language processing that require learning of temporal signals. To address these require- ments, we need deep neuromorphic architectures with recurrent connections such as deep recurrent neural networks. However, the training of such networks demand very high pre- cision of weights, excellent conductance linearity and low write-noise- not satisfied by current memristive implementations. Inspired from optogenetics, here we report a neuromorphic computing platform comprised of photo-excitable neuristors capable of in-memory compu- tations across 980 addressable states with a high signal-to-noise ratio of 77. The large linear dynamic range, low write noise and selective excitability allows high fidelity opto-electronic transfer of weights with a two-shot write scheme, while electrical in-memory inference provides energy efficiency. This method enables implementing a memristive deep recurrent neural network with twelve trainable layers with more than a million parameters to recognize spoken commands with >90% accuracy. 1 School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore. 2 School of Electrical and Electronic Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore.
    [Show full text]
  • Optogenetics
    EUROSCIENCE NWINTER 2010 QUARTERLY Message from the President “Research moves If We Are Not for Science, Who Will Be for Us? nations forward, The outlook for scientific funding in the year ahead is fraught with uncertainty. On one hand, we are living through a time of gives patients hope, unparalleled scientific opportunity. On the other, we are facing deep economic stresses and unrelenting competition for limited and directly serves resources. This is a hard truth not just in America, but through- the long-term out the world. health and economic In these times, there is a demonstrable risk that science will be Michael E. Goldberg, forced to shelve or delay potentially game-changing progress. needs of all nations.” SfN President Labs could disband, or turn away the next generation’s great minds. It could mean flat or falling employment for the broader — Michael E. Goldberg, scientific enterprise — scientists, plus the technicians, machinists, administrators, and SfN President support staff who make it all possible. As an SfN member, you have potential to help change this scenario although scientists do not control the federal purse. The answer is sustained communication, advocacy, and action. To be sure, we face tough head winds and a lot of competition. But what will each one of us do today to create a world where flat funding of science is eventually IN THIS ISSUE impossible? Where every nation strongly invests in science as a force for better knowl- edge and more progress? Continued on page 2 . Message from the President ................................ 1 Inside Science: Optogenetics ................................ 1 Inside Science SfN Recognizes Leadership in Support of Research ............................................
    [Show full text]
  • Optogentic Neuromodulation in Animal Models Of
    Optogenetic Neuromodulation in a Rodent Model of Depression Inaugural-Dissertation zur Erlangung der Doktorwürde der Fakultät für Biologie der Albert–Ludwigs–Universität Freiburg im Breisgau vorgelegt von Lisa-Marie Pfeiffer aus Kassel Freiburg im Breisgau September 2019 Angefertigt in der Abteilung für Stereotaktische und Funktionelle Neurochirur- gie des Universitätsklinikums Freiburg unter der Leitung von Prof. Dr. med. Volker A. Coenen und PD Dr. Máté D. Döbrössy. Dekan der Fakultät für Biologie: Prof. Dr. Wolfgang Driever Promotionsvorsitzender: Prof. Dr. Andreas Hiltbrunner Betreuer der Arbeit: Prof. Dr. med. Volker A. Coenen Betreuer der biologischen Fakultät: Prof. Dr. Wolfgang Driever Referent: Prof. Dr. Wolfgang Driever Koreferentin: Prof. Dr. Ilka Diester Drittprüferin: Prof. Dr. Carola Haas Datum der mündlichen Prüfung: 28.11.2019 To Mom and Dad. “Rabbit’s clever," said Pooh thoughtfully. "Yes," said Piglet, "Rabbit’s clever." "And he has Brain." "Yes," said Piglet, "Rabbit has Brain." There was a long silence. "I suppose," said Pooh, "that that’s why he never understands anything.” — A.A. Milne, Winnie-the-Pooh I Contents Contents List of TablesVI List of Figures VII ErklärungIX AbstractX Deutsche Zusammenfassung XII 1 Introduction1 1.1 Neuromodulation in psychiatric diseases . .1 1.2 Major Depression . .2 1.2.1 The Neurobiology of Depression . .3 1.2.1.1 (Epi-) Genetics and Environmental Factors . .4 1.2.1.2 Monoamine Deficiency Theory . .5 1.2.1.3 Stress Hypothesis . .6 1.2.1.4 Dysbalanced Neurotrophins and Neurogenesis . .7 1.2.1.5 Inflammation Theory . .8 1.2.1.6 Gut Microbiota Theory . .8 1.2.1.7 Dysregulation of the Reward Circuitry .
    [Show full text]
  • Shielded Coaxial Optrode Arrays for Neurophysiology
    ORIGINAL RESEARCH published: 09 June 2016 doi: 10.3389/fnins.2016.00252 Shielded Coaxial Optrode Arrays for Neurophysiology Jeffrey R. Naughton 1, Timothy Connolly 2, Juan A. Varela 3, Jaclyn Lundberg 3, Michael J. Burns 1, Thomas C. Chiles 2, John P. Christianson 3 and Michael J. Naughton 1* 1 Department of Physics, Boston College, Chestnut Hill, MA, USA, 2 Department of Biology, Boston College, Chestnut Hill, MA, USA, 3 Department of Psychology, Boston College, Chestnut Hill, MA, USA 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 Edited by: pathways emanating from specific cell stimulation. Here, we introduce a coaxial electrode Ramona Samba, architecture that is uniquely suited to address these issues, as it can simultaneously Natural and Medical Sciences Institute, Germany be utilized as an optical waveguide and a shielded electrode in dense arrays. Using Reviewed by: optogenetically-transfected cells on a coaxial MEA, we demonstrate the utility of the Joost Le Feber, architecture by recording cellular currents evoked from optical stimulation. We also show University of Twente, Netherlands Marco Canepari, the capability for network recording by radiating an area of seven individually-addressed Institut National de la Santé et de la coaxial electrode regions with cultured cells covering a section of the extent.
    [Show full text]