2017

June, 2017
Journal of Neurodevelopmental Disorders

Vagus nerve stimulation as a potential adjuvant to behavioral therapy for autism and other neurodevelopmental disorders
Vagus nerve stimulation (VNS) is an FDA approved therapy that is safe and effective in reducing seizurefrequency and duration in individuals with epilepsy. Individuals with neurodevelopmental disorders often exhibitdecreased vagal tone, and studies indicate that VNS can be used to overcome an insufficient vagal response. Multiplestudies have also docum ented si gnifi cant imp rovements in quality of life after VNS therapy in individuals wi thneurodevelop mental diso rders. Moreover, recent f inding s indicate that VNS significantly enhances the b enefitsof rehabilitative training in animal models and patients, leading to greater recovery in a variety of neurological diseases.Here, we review these findings and provide a discussion of how VNS paired with rehabilitation may yield benefits inthe context of neurodevelopmental disorders.
Crystal T. Engineer, Seth A. Hays and Michael P. Kilgard

May 2, 2017
Journal of Neurotrauma

Traumatic brain injury occludes training-dependent cortical reorganization in the contralesional hemisphere
Rehabilitative training drives plasticity in the ipsilesional (injured) motor cortex that is believed to support recovery of motor function after either stroke or TBI.  In addition, adaptive plasticity in the contralesional (uninjured) motor cortex has been well‐ characterized in the context of stroke. While similar rehabilitation‐dependent plasticity in the intact hemisphere may occur after TBI, this has yet to be thoroughly explored.    In this study, we investigated the effects of TBI and forelimb training on reorganization of movement representations in the intact motor cortex.  Rats were trained to proficiency on the isometric pull task and then received a controlled‐cortical impact (CCI) in the left motor cortex to impair function of the trained right forelimb.  After TBI, animals underwent forelimb training on the pull task for two months. At the end of training, intracortical microstimulation (ICMS) was used to document the organization of the intact motor cortex (the contralesional hemisphere).  TBI significantly decreased the cortical area eliciting movements of the impaired forelimb in untrained animals.  In the absence of TBI, training significantly increased forelimb map area compared to untrained controls.   However, training of the impaired forelimb after TBI was insufficient to increase forelimb map area.  These findings are consistent with other studies showing impaired rehabilitation‐dependent plasticity after TBI and provide a novel characterization of TBI on rehabilitation‐dependent plasticity in contralesional motor circuits.    
Mr. David Pruitt, Miss Tanya Danaphongse, Ms. Ariel Schmid, Mr. Robert Morrison, Dr. Michael Kilgard, Dr. Robert L Rennaker II, and Dr. Seth Hays.

March, 2017
Experimental Neurology

Parametric characterization of neural activity in the locus coeruleus in response to vagus nerve stimulation
In this study, we recorded neural activity in the LC and the mesencephalic trigeminal nucleus (Me5) in response to VNS over a broad range of current amplitudes, pulse frequencies, train durations, inter-train intervals, and pulse widths. Brief 0.5 s trains of VNS drive rapid, phasic firing of LC neurons at 0.1 mA. Higher current intensities and longer pulse widths drive greater increases in LC firing rate. Varying the pulse frequency substantially affects the timing, but not the total amount, of phasic LC activity. VNS drives pulse-locked neural activity in the Me5 at current levels above 1.2 mA. These results provide insight into VNS-evoked phasic neural activity in multiple neural structures and may be useful in guiding the selection of VNS parameters to enhance clinical efficacy.
Daniel R. Hulsey, Jonathan R. Riley, Kristofer W. Loerwald, Robert L. Rennaker II, Michael P. Kilgarda, Seth A. Hays

January 30, 2017
JAMA Neurology

Retinal Architecture and Melanopsin-Mediated Pupillary Response Characteristics: A Putative Pathophysiologic Signature for the Retino-Hypothalamic Tract in Multiple Sclerosis
In this case-control study, attenuation of the melanopsin-mediated sustained pupillary constriction response was significantly associated with thinning of the GCL + IPL sector of the retina in the eyes of patients with MS, particularly those with a history of acute optic neuritis. Melanopsin-containing ganglion cells in the retina represent, at least in part, the composition of the retinohypothalamic tract. As such, our findings may signify the ability to elucidate a putative surrogate neurophysiologic signature that correlates with a constellation of homeostatic mechanisms in both health and illness.
Ethan MeltzerPeter V. SguignaAdnan SubeiShin BehEric KildebeckDarrel Conger1Amy CongerMarlen LuceroBenjamin S. FrohmanAshley N. FrohmanShiv SaidhaSteven GalettaPeter A. Calabresi, Robert RennakerTeresa C. FrohmanRandy H. KardonLaura J. BalcerElliot M. Frohman

January 11, 2017
Brain Stimulations

Temporal plasticity in auditory cortex improves neural discrimination of speech sounds
Many individuals with language learning impairments exhibit temporal processing deficits and degraded neural responses to speech sounds. Auditory training can improve both the neural and behavioral deficits, though significant deficits remain. Recent evidence suggests that vagus nerve stimulation (VNS) paired with rehabilitative therapies enhances both cortical plasticity and recovery of normal function.
Crystal T. EngineerJai A. Shetake, Navzer D. Engineer, Will A. Vrana, Jordan T. Wolf, Michael P. Kilgard

January 3, 2017

Patent
Methods, systems, and devices for pairing vagus nerve stimulation with motor therapy in stroke patients

January 1, 2017
Muscle and Nerve

Median and ulnar nerve injuries reduce volitional forelimb strength in rats
Peripheral nerve injuries (PNI) are among the leading causes of physical disability in the United States. The majority of injuries occur in the upper extremities, and functional recovery is often limited. Robust animal models are critical first steps for developing effective therapies to restore function after PNI.
Eric C. Meyers MS, Rafael Granja MD, Bleyda R. Solorzano BS, Mario Romero-Ortega PhD, Michael P. Kilgard PhD, Robert L. Rennaker II PhD, Seth Hays PhD

January 1, 2017
Journal of Biomedical Materials Research

Design and demonstration of an intracortical probe technology with tunable modulus
Intracortical probe technology, consisting of arrays of microelectrodes, offers a means of recording the bioelectrical activity from neural tissue. A major limitation of existing intracortical probe technology pertains to limited lifetime of 6 months to a year of recording after implantation. A major contributor to device failure is widely believed to be the interfacial mechanical mismatch of conventional stiff intracortical devices and the surrounding brain tissue. We describe the design, development, and demonstration of a novel functional intracortical probe technology that has a tunable Young's modulus from ∼2 GPa to ∼50 MPa.
Dustin M. Simon, Hamid Charkhkar, Conan St. John, Sakthi Rajendran, Tong Kang, Radu Reit, David Arreaga-Salas, Daniel G. McHail, Gretchen L. Knaack, Andrew Sloan, Dane Grasse, Theodore C. Dumas, Robert L. Rennaker, Joseph J. Pancrazio, Walter E. Voit

2016

October 15, 2016
Behavioural Brain Research

Forelimb training drives transient map reorganization in ipsilateral motor cortex
Skilled motor training results in reorganization of contralateral motor cortex movement representations. The ipsilateral motor cortex is believed to play a role in skilled motor control, but little is known about how training influences reorganization of ipsilateral motor representations of the trained limb.
Pruitt DTSchmid ANDanaphongse TTFlanagan KEMorrison RAKilgard MPRennaker RL 2ndHays SA

August 30, 2016
Neurorehabilitation and Neural Repair

Vagus Nerve Stimulation During Rehabilitative Training Improves Forelimb Recovery After Chronic Ischemic Stroke in Rats
Stroke is a leading cause of long-term disability. Currently, there are no consistently effective rehabilitative treatments for chronic stroke patients. Our recent studies demonstrate that vagus nerve stimulation (VNS) paired with rehabilitative training improves recovery of function in multiple models of stroke.
Khodaparast NKilgard MPCasavant RRuiz AQureshi IGanzer PDRennaker RL 2ndHays SA

July 1, 2016
Behavioural Brain Research

Awake behaving electrophysiological correlates of forelimb hyperreflexia, weakness and disrupted muscular synchronization following cervical spinal cord injury in the rat
Spinal cord injury usually occurs at the level of the cervical spine and results in profound impairment of forelimb function. In this study, we recorded awake behaving intramuscular electromyography (EMG) from the biceps and triceps muscles of the impaired forelimb during volitional and reflexive forelimb movements before and after unilateral cervical spinal cord injury (cSCI) in rats.
Ganzer PDMeyers ECSloan AMMaliakkal RRuiz AKilgard MPRobert LR 2nd

July, 2016
Neurobiology of Aging

Vagus nerve stimulation during rehabilitative training enhances recovery of forelimb function after ischemic stroke in aged rats
Advanced age is associated with a higher incidence of stroke and worse functional outcomes. Vagus nerve stimulation (VNS) paired with rehabilitative training has emerged* as a potential method to improve recovery after brain injury but to date has only been evaluated in young rats.
Hays SARuiz ABethea TKhodaparast NCarmel JBRennaker RL 2ndKilgard MP

June 15, 2016
Journal of Neuroscience Methods

The supination assessment task: An automated method for quantifying forelimb rotational function in rats
Neurological injuries or disease can impair the function of motor circuitry controlling forearm supination, and recovery is often limited. Preclinical animal models are essential tools for developing therapeutic interventions to improve motor function after neurological damage.
Meyers ESindhurakar AChoi RSolorzano RMartinez TSloan ACarmel JKilgard MPRennaker RL 2ndHays S

May 26, 2016

Patent
Methods and systems for therapy of multiple sclerosis

May 1, 2016
Journal of Neurotrauma

Vagus Nerve Stimulation Delivered with Motor Training Enhances Recovery of Function after Traumatic Brain Injury
Traumatic Brain Injury (TBI) is one of the largest health problems in the United States, and affects nearly 2 million people every year. The effects of TBI, including weakness and loss of coordination, can be debilitating and last years after the initial injury.
Pruitt DTSchmid ANKim LJAbe CMTrieu JLChoua CHays SAKilgard MPRennaker RL

April 27, 2016
The Journal of Neuroscience

Knockdown of Dyslexia-Gene Dcdc2 Interferes with Speech Sound Discrimination in Continuous Streams
Dyslexia is the most common developmental language disorder and is marked by deficits in reading and phonological awareness. One theory of dyslexia suggests that the phonological awareness deficit is due to abnormal auditory processing of speech sounds.
Centanni TMBooker ABChen FSloan AMCarraway RSRennaker RLLoTurco JJKilgard MP

April 13, 2016
Neurotherapeutics

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation
Pathological neural activity could be treated by directing specific plasticity to renormalize circuits and restore function. Rehabilitative therapies aim to promote adaptive circuit changes after neurological disease or injury, but insufficient or maladaptive plasticity often prevents a full recovery.
Hays SA

April, 2016
Brain Stimulation

Reorganization of Motor Cortex by Vagus Nerve Stimulation Requires Cholinergic Innervation
Vagus nerve stimulation (VNS) paired with forelimb training drives robust, specific reorganization of movement representations in the motor cortex. The mechanisms that underlie VNS-dependent enhancement of map plasticity are largely unknown.
Hulsey DRHays SAKhodaparast NRuiz ADas PRennaker RL 2ndKilgard MP

February 23, 2016

Patent
Methods, systems, and devices for treating tinnitus with VNS pairing

February 17, 2016
The Journal of Neuroscience

Selective Disruption of Metabotropic Glutamate Receptor 5-Homer Interactions Mimics Phenotypes of Fragile X Syndrome in Mice
Altered function of the Gq-coupled, Group 1 metabotropic glutamate receptors, specifically mGlu5, is implicated in multiple mouse models of autism and intellectual disability. mGlu5 dysfunction has been most well characterized in the fragile X syndrome mouse model, the Fmr1 knock-out (KO) mouse, where pharmacological and genetic reduction of mGlu5 reverses many phenotypes. mGlu5 is less associated with its scaffolding protein Homer in Fmr1 KO mice, and restoration of mGlu5-Homer interactions by genetic deletion of a short, dominant negative of Homer, H1a, rescues many phenotypes of Fmr1 KO mice.
Guo WMolinaro GCollins KAHays SAPaylor RWorley PFSzumlinski KKHuber KM

January 30, 2016
Journal of Neuroscience Methods

An Automated Task for the Training and Assessment of Distal Forelimb Function in a Mouse Model of Ischemic Stroke
Behavioral models relevant to stroke research seek to capture important aspects of motor skills typically impaired in human patients, such as coordination of distal musculature. Such models may focus on mice since many genetic tools are available for use only in that species, and since the training and behavioral demands of mice can differ from rats even for superficially similar behavioral readouts.
April M. BeckerEric MeyersAndrew SloanRobert RennakerMichael KilgardMark P. Goldberg

January, 2016
Brain Stimulation

Cortical Map Plasticity as a Function of Vagus Nerve Stimulation Intensity
The primary goal of this study was to determine the range of VNS intensities that can be used to direct cortical map plasticity.
Borland MSVrana WAMoreno NAFogarty EABuell EPSharma PEngineer CTKilgard MP

January, 2016
Stroke

Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke
Recent animal studies demonstrate that vagus nerve stimulation (VNS) paired with movement induces movement-specific plasticity in motor cortex and improves forelimb function after stroke.
Jesse Dawson, David Pierce, Anand Dixit, Teresa J. Kimberley, Michele Robertson, Brent Tarver, Omar Hilmi,, John McLean, Kirsten Forbes, Michael P. Kilgard, Robert L. Rennaker, Steven C. Cramer, Matthew Walters and Navzer Engineer

2015

December 17, 2015

Patent
A helmet having an outer shell and an inner shell placed within the outer shell. The inner shell attached to the outer shell by a plurality of elastomeric elements to isolate the inner shell from impacts and rotational forces applied to the outer shell.

November 17, 2015

Integration of High-Charge-Injection-Capacity Electrodes onto Polymer Softening Neural Interfaces
Softening neural interfaces are implanted stiff to enable precise insertion, and they soften in physiological conditions to minimize modulus mismatch with tissue. In this work, a high-charge-injection-capacity iridium electrode fabrication process is detailed.
David E. Arreaga-SalasAdrian Avendaño-BolívarDustin SimonRadu ReitAldo Garcia-SandovalRobert L. Rennaker, and Walter Voit

November 4, 2015
Neurorehabilitation and Neural Repair

Vagus Nerve Stimulation During Rehabilitative Training Improves Forelimb Recovery After Chronic Ischemic Stroke in Rats
Stroke is a leading cause of long-term disability. Currently, there are no consistently effective rehabilitative treatments for chronic stroke patients. Our recent studies demonstrate that vagus nerve stimulation (VNS) paired with rehabilitative training improves recovery of function in multiple models of stroke.
Navid Khodaparast, Michael P. Kilgard, Reema Casavant, Andrea Ruiz, Iqra Qureshi, Patrick D. Ganzer, Robert L. Rennaker II, Seth A. Hays

November, 2015
Neurobiology of Disease

Degraded neural and behavioral processing of speech sounds in a rat model of Rett syndrome
Individuals with Rett syndrome have greatly impaired speech and language abilities. Auditory brainstem responses to sounds are normal, but cortical responses are highly abnormal.
Crystal T. EngineerKimiya C. RahebiMichael S. BorlandElizabeth P. BuellTracy M. Centanni, Melyssa K. FinkKwok W. ImLinda G. WilsonMichael P. Kilgard

October 27, 2015

A Within-Animal Comparison of Skilled Forelimb Assessments in Rats
A variety of skilled reaching tasks have been developed to evaluate forelimb function in rodent models. The single pellet skilled reaching task and pasta matrix task have provided valuable insight into recovery of forelimb function in models of neurological injury and disease. Recently, several automated measures have been developed to reduce the cost and time burden of forelimb assessment in rodents.
Andrew M. Sloan, Melyssa K. Fink, Amber J. Rodriguez, Adam M. Lovitz, Navid Khodaparast, Robert L. Rennaker, Seth A. Hays

October 17, 2015
Journal of Neuroscience Methods

An Automated Task for the Training and Assessment of Distal Forelimb Function in a Mouse Model of Ischemic Stroke
Behavioral models relevant to stroke research seek to capture important aspects of motor skill typically impaired in human patients, such as coordination of distal musculature. Such models may focus on mice since many genetic tools are available for use only in that species, and since the training and behavioral demands of mice can differ from rats even for superficially similar behavioral readouts.
Andrew M. Sloan , Melyssa K. Fink, Amber J. Rodriguez, Adam M. Lovitz, Navid Khodaparast, Robert L. Rennaker, Seth A. Hays

September 23, 2015

Retinal oximetry: a novel visual biomarker of retinal metabolic dysfunction in MS
Optic neuropathy occurs very commonly in multiple sclerosis (MS) patients. Optical coherence tomography (OCT) has been shown to be a sensitive, and precise method of quantifying structural retinal changes that occur in MS. It is very likely, however, that metabolic dysfunction precedes such structural changes in the retina; therefore, a method of detecting and measuring these metabolic changes (for example, retinal oxygen utilization) would result in a more sensitive visual biomarker of MS disease activity.
S.C. Beh , M. Lucero , D. Conger , A. Conger , V. Stokes , T.C. Frohman , P.A. Calabresi , R. Rennaker , L.J. Balcer , E.M. Frohman

September 15, 2015
Nature Reviews Neurology

Ocular motor signatures of cognitive dysfunction in multiple sclerosis
The anatomical and functional overlap between ocular motor command circuitry and the higher-order networks that form the scaffolding for cognition makes for a compelling hypothesis that measures of ocular motility could provide a means to sensitively interrogate cognitive dysfunction in people with multiple sclerosis (MS).
Joanne Fielding, Meaghan Clough, Shin Beh, Lynette Millist, Derek Sears, Ashley N. Frohman, Nathaniel Lizak, Jayne Lim, Scott Kolbe, Robert L. Rennaker II, Teresa C. Frohman, Owen B. WhiteElliot M. Frohman

September 3, 2015

Patent
System for acceleration measurements and traumatic brain injury detection

September 3, 2015

Patent
System for traumatic brain injury detection using oculomotor tests

July 28, 2015

Patent
Methods for enhancing exposure therapy using vagus nerve stimulation

July 28, 2015

Patent
Systems, methods and devices for paired plasticity

July 1, 2015
Behavioural Brain Research

Speech training alters consonant and vowel responses in multiple auditory cortex fields
Speech sounds evoke unique neural activity patterns in primary auditory cortex (A1). Extensive speech sound discrimination training alters A1 responses. While the neighboring auditory cortical fields each contain information about speech sound identity, each field processes speech sounds differently.
Engineer CTRahebi KCBuell EPFink MKKilgard MP

June 2015
Journal of Neuroscience Research

Activation of the anti-inflammatory reflex blocks lipopolysaccharide-induced decrease in synaptic inhibition in the temporal cortex of the rat
Stress is a potential trigger for a number of neuropsychiatric conditions, including anxiety syndromes and schizophrenic psychoses. The temporal neocortex is a stress-sensitive area involved in the development of such conditions.
Garcia-Oscos FPeña DHousini MCheng DLopez DCuevas-Olguin RSaderi NSalgado Delgado RGalindo Charles LSalgado Burgos HRose-John SFlores GKilgard MPAtzori M.

May/June 2015
Brain Stimulation

Pairing Speech Sounds With Vagus Nerve Stimulation Drives Stimulus-specific Cortical Plasticity
Individuals with communication disorders, such as aphasia, exhibit weak auditory cortex responses to speech sounds and language impairments. Previous studies have demonstrated that pairing vagus nerve stimulation (VNS) with tones or tone trains can enhance both the spectral and temporal processing of sounds in auditory cortex, and can be used to reverse pathological primary auditory cortex (A1) plasticity in a rodent model of chronic tinnitus.
Engineer CTEngineer NDRiley JRSeale JDKilgard MP

April 21, 2015
Otology & Neurotology

Placebo-Controlled Vagus Nerve Stimulation Paired With Tones in a Patient With Refractory Tinnitus: A Case Report
Classical neuromodulation consists of applying electrical or magnetic stimuli to the nervous system to modulate ongoing activity and connectivity. However, recently, an exciting novel neuromodulation technique was developed in which stimulation of the vagal nerve was paired with simultaneous presentation of tones, demonstrating that it reverses a tinnitus percept in noise-exposed rats.
De Ridder DKilgard MEngineer NVanneste S

April, 2015
Otology & Neurotology

Vagus Nerve Stimulation and Rehabilitation Improves Recovery of A Motor Task after Neurological Injury
Ischemic stroke and spinal cord injury are neurological injuries that produce persisting motor deficits. Additionally,the majority of those suffering from impairments due to ischemic stroke or spinal cord injury rarely fully recover complete function with current treatment options. Here, we investigate the use of vagus nerve stimulation (VNS), which facilitates specific and long-lasting plasticity after injury.
Rachel Choi, Eric Meyers, Patrick Ganzer, Seth Hays, Michael Kilgard, Robert Rennaker

February 1, 2015
Stroke

Vagus Nerve Stimulation Improves Motor Function After Chronic Stroke in Adult Rats
Stroke is the leading cause of serious long-term disability. Currently, there is no effective treatment for chronic stroke patients. Neuroplasticity within motor circuitry is believed to support recovery of function after stroke. We have developed a method using vagus nerve stimulation (VNS) paired with motor training to drive robust, specific plasticity in the motor cortex.
Navid Khodaparast, Reema Casavant, Andrea Ruiz, Robert L Rennaker and Michael P Kilgard

February 1, 2015
Stroke

Vagus Nerve Stimulation Enhances Neuroplasticity and Forelimb Recovery after Stroke in Aged Rats
Advanced age is a leading risk factor for stroke and is associated with worse recovery. The goal of post-stroke rehabilitative therapies is to enhance neuroplasticity to support the recovery of motor function. Recent studies indicate that vagus nerve stimulation (VNS) paired with rehabilitative training drives robust plasticity and results in significantly enhanced recovery of forelimb function in multiple models of brain injury in young rats.
Seth A Hays, Andrea Ruiz, Daniel R Hulsey, Navid Khodaparast, Thelma Bethea, Jason B Carmel, Robert L Rennaker and Michael P Kilgard

January 13, 2015

Patent
Systems, methods and devices for treating tinnitus

January, 2015
Brain, Behavior, and Immunity

Vagal nerve stimulation blocks interleukin 6-dependent synaptic hyperexcitability induced by lipopolysaccharide-induced acute stress in the rodent prefrontal cortex
The ratio between synaptic inhibition and excitation (sI/E) is a critical factor in the pathophysiology of neuropsychiatric disease. We recently described a stress-induced interleukin-6 dependent mechanism leading to a decrease in sI/E in the rodent temporal cortex. The aim of the present study was to determine whether a similar mechanism takes place in the prefrontal cortex, and to elaborate strategies to prevent or attenuate it.
Garcia-Oscos FPeña DHousini MCheng DLopez DBorland MSSalgado-Delgado RSalgado HD'Mello SKilgard MP, Rose-John SAtzori M

2014

2014

A 700mV low power low noise implantable neural recording system design
A low power, low noise implantable neural recording interface for use in a Radio-Frequency Identification (RFID) is presented in this paper. A two stage neural amplifier and 8 bit Pipelined Analog to Digital Converter (ADC) are integrated in this system.
An GHutchens CRennaker RL 2nd

November 18, 2014
Neuroscience 2014

Pairing vagus nerve stimulation with rehabilitative training enhances functional recovery after traumatic brain injury
Traumatic Brain Injury (TBI) is one of the largest health problems in the United States, and affects nearly two million people every year. The effects of TBI, including weakness and loss of coordination, can be observed years after the initial injury. We have developed a method by which we drive cortical plasticity through stimulation of the vagus nerve during rehabilitative therapy to enhance recovery from TBI.
D. Pruitt, A. Schmid, C. Choua, L. Kim, J. Trieu, C. Abe, K. Flanagan, M. Kilgard, R. L. Rennaker, II;

November 12, 2014
Frontiers in Behavioral Neuroscience

Abnormal emotional learning in a rat model of autism exposed to valproic acid in utero
Autism Spectrum Disorders (ASD) are complex neurodevelopmental disorders characterized by repetitive behavior and impaired social communication and interactions. Apart from these core symptoms, a significant number of ASD individuals display higher levels of anxiety and some ASD individuals exhibit impaired emotional learning.
Banerjee A, Engineer CT, Sauls BL, Morales AA, Kilgard MP, Ploski JE

September 25, 2014
Frontiers in Behavioral Neuroscience

An analog front-end circuit with spike detection for implantable neural recording system design
A low power, low noise implantable neural recording interface for use in a power harvested inductive coupling system is presented in this paper. A two stage neural amplifier, selective reference thresholder and a serial communication interface form the neural data logger.
Guanglei An, De Kanishka, Cheng Hao, Rehan Ahmed, Chriswell Hutchens, Robert L. Rennaker

September 18, 2014
Frontiers in Behavioral Neuroscience

Vagus nerve stimulation enhances extinction of conditioned fear and modulates plasticity in the pathway from the ventromedial prefrontal cortex to the amygdala
Fearful experiences can produce long-lasting and debilitating memories. Extinction of the fear response requires consolidation of new memories that compete with fearful associations.
Peña DFChilds JEWillett SVital AMcIntyre CKKroener S

August 14, 2014

Patent
Methods, systems, and devices for pairing vagus nerve stimulation with motor therapy in stroke patients

August 21, 2014
Stroke

Vagus Nerve Stimulation During Rehabilitative Training Improves Functional Recovery After Intracerebral Hemorrhage
VNS paired with rehabilitative training significantly improved recovery of forelimb function when compared with rehabilitative training without VNS.
Seth A. Hays, Navid Khodaparast, Daniel R. Hulsey, Andrea Ruiz, Andrew M. Sloan, Robert L. Rennaker and Michael P. Kilgard

August 5, 2014
Frontiers in Systems Neuroscience

Speech sound discrimination training improves auditory cortex responses in a rat model of autism
Children with autism often have language impairments and degraded cortical responses to speech. Extensive behavioral interventions can improve language outcomes and cortical responses.
Engineer CTCentanni TMIm KWKilgard MP

August 1, 2014
Brain Research

Controlled-cortical impact reduces volitional forelimb strength in rats
Traumatic brain injury (TBI) is one of the largest health problems in the United States and affects both cognitive and motor function. Although weakness is common in TBI patients, few studies have demonstrated a reduction in strength in models of brain injury.
David PruittSeth HaysAriel SchmidConnie ChouaLily KimJenny Trieu, Michael P. KilgardRobert L. Rennaker II

July 31, 2014

Implanted Miniaturized Antenna for Brain Computer Interface Applications: Analysis and Design
Implantable Brain Computer Interfaces (BCIs) are designed to provide real-time control signals for prosthetic devices, study brain function, and/or restore sensory information lost as a result of injury or disease.
Yujuan Zhao, Robert L. Rennaker, Chris Hutchens, Tamer S. Ibrahim

July 28, 2014
Ear and Hearing

Behavioral and Neural Discrimination of Speech Sounds After Moderate or Intense Noise Exposure in Rats
Hearing loss is a commonly experienced disability in a variety of populations including veterans and the elderly and can often cause significant impairment in the ability to understand spoken language. In this study, we tested the hypothesis that neural and behavioral responses to speech will be differentially impaired in an animal model after two forms of hearing loss.
Reed ACCentanni TMBorland MSMatney CJEngineer CTKilgard MP

June 18, 2014
NeuroReport

The timing and amount of vagus nerve stimulation during rehabilitative training affect post-stroke recovery of forelimb strength
Loss of upper arm strength after stroke is a leading cause of disability. Strategies that can enhance the benefits of rehabilitation training could improve motor function after stroke.
Hays, Seth A.; Khodaparast, Navid; Ruiz, Andrea; Sloan, Andrew M.; Hulsey, Daniel R.; Rennaker, Robert L. II; Kilgard, Michael P.

June 17, 2014
Journal of Neurotrauma

Controlled-Cortical Impact Reduces Rats Ability to Sustain Application of Submaximal Force
Traumatic brain injury (TBI) is an increasingly large health risk in the United States and often results in a severe lack of motor control and weakness. We have recently reported that experimental TBI in rats induces a chronic impairment in maximal volitional forelimb strength. Many activities of daily living, however, require consistent application of controlled submaximal force rather than maximal force.
C. Choua, A. Schmid, L. Kim, J. Trieu, D. Machuca, S. Sterling, S. Shah, S. Khan, D. Pruitt, R.L. Rennaker II

June 17, 2014
Journal of Neurotrauma

Vagus Nerve Stimulation and Nonparetic Limb Training Modify Stroke Recovery
Vagus nerve stimulation (VNS) is a safe, tolerable treatment that has been shown to drive powerful, long-lasting plasticity especially when paired with somatosensory inputs. VNS paired with rehabilitative training has been shown to improve functional recovery beyond what can be achieved by rehabilitative training alone in models of stroke.
A. Nguyen, N. Khodaparast, S.A. Hays, M.P. Kilgard, R.L. Rennaker

May 28, 2014

Speech Sound Processing Deficits and Training-Induced Neural Plasticity in Rats with Dyslexia Gene Knockdown
In utero RNAi of the dyslexia-associated gene Kiaa0319 in rats (KIA-) degrades cortical responses to speech sounds and increases trial-by-trial variability in onset latency.
Tracy M. Centanni , Fuyi Chen, Anne M. Booker, Crystal T. Engineer, Andrew M. Sloan, Robert L. Rennaker, Joseph J. LoTurco, Michael P. Kilgard

April 16, 2014
The Journal of Neuroscience

Environmental Acoustic Enrichment Promotes Recovery from Developmentally Degraded Auditory Cortical Processing
It has previously been shown that environmental enrichment can enhance structural plasticity in the brain and thereby improve cognitive and behavioral function. In this study, we reared developmentally noise-exposed rats in an acoustic-enriched environment for ∼4 weeks to investigate whether or not enrichment could restore developmentally degraded behavioral and neuronal processing of sound frequency.
Xiaoqing Zhu, Fang Wang, Huifang Hu, Xinde Sun, Michael P. Kilgard, Michael M. Merzenich, and Xiaoming Zhou

April 5, 2014
Brain Research

Degraded speech sound processing in a rat model of fragile X syndrome
Fragile X syndrome is the most common inherited form of intellectual disability and the leading genetic cause of autism. Impaired phonological processing in fragile X syndrome interferes with the development of language skills. 
Crystal T. Engineer, , Tracy M. Centanni, Kwok W. Im, Kimiya C. Rahebi, Elizabeth P. Buell, Michael P. Kilgard

April 4, 2014
Developmental Neurobiology

Degraded auditory processing in a rat model of autism limits the speech representation in non-primary auditory cortex
Although individuals with autism are known to have significant communication problems, the cellular mechanisms responsible for impaired communication are poorly understood.
Engineer CTCentanni TMIm KWBorland MSMoreno NACarraway RSWilson LGKilgard MP

February 20, 2014
Encyclopedia of Computational Neuroscience

Neural Coding of Speech Sounds
Speech sounds are composed of both rapid spectrotemporal changes and slow steady-state portions. The neural coding of speech sounds involves the representation of precise action potential timing across many cortical areas. Behavioral speech sound discrimination accuracy is well predicted by quantifying the similarity between the spatiotemporal response patterns evoked by two sounds.
Michael Kilgard

February 18, 2014
Neurorehabilitation and Neural Repair

Vagus Nerve Stimulation Delivered During Motor Rehabilitation Improves Recovery in a Rat Model of Stroke
Neural plasticity is widely believed to support functional recovery following brain damage.
Navid Khodaparast, PhD, Seth A. Hays, PhD, Andrew M. Sloan, PhD, Tabbassum Fayyaz, Daniel R. Hulsey, Robert L. Rennaker II, PhD, Michael P. Kilgard, PhD

February 1, 2014
Stroke

A Novel Means of Augmenting Motor Recovery After Ischemic Stroke; Vagus Nerve Stimulation (VNS) Paired with Intensive Upper Limb Rehabilitation
Chronic upper limb impairment is a major predictor of poor functional outcome after stroke. We have developed a rehabilitation intervention to address this issue. It pairs VNS with intensive upper limb training. Our hypothesis is that short bursts of VNS, specifically timed during therapy, will drive cortical plasticity and improve clinical outcomes via timely release of neuromodulators such as acetylcholine and norepinephrine.

February, 2014
Neuromodulation

Safety and efficacy of vagus nerve stimulation paired with tones for the treatment of tinnitus: a case series
Classical neuromodulation applies current to the nervous system in an attempt to alter ongoing activity. However, classical neuromodulation interferes with activity but does not drive it in a controlled way. Recently, an animal study demonstrated it is possible to drive plasticity in a controlled way by using stimulation of the vagus nerve paired with tones. This reversed the tinnitus percept and pathological neural plasticity in noise-exposed rats with behavioral characteristics of tinnitus. The aim of the current study was to translate this innovative neuromodulation method to humans suffering from tinnitus.
De Ridder DVanneste SEngineer NDKilgard MP

January 31, 2014
Neuroscience

Detection and identification of speech sounds using cortical activity patterns
We have developed a classifier capable of locating and identifying speech sounds using activity from rat auditory cortex with an accuracy equivalent to behavioral performance and without the need to specify the onset time of the speech sounds.
T.M. Centanni, , A.M. Sloan, A.C. Reed, C.T. Engineer, R.L. Rennaker II, M.P. Kilgard

January 2014
Behavioural Brain Research

Speech training alters tone frequency tuning in rat primary auditory cortex
Previous studies in both humans and animals have documented improved performance following discrimination training.
Crystal T. Engineer, , Claudia A. Perez, Ryan S. Carraway, Kevin Q. Chang, Jarod L. Roland, Michael P. Kilgard

2013

2013

Targeting Plasticity with Vagus Nerve Stimulation to Treat Neurological Disease
Pathological neural activity in a variety of neurological disorders could be treated by directing plasticity to specifically renormalize aberrant neural circuits, thereby restoring normal function.
Seth A. Hays, Robert L. Rennaker, Michael P. Kilgard

December, 2013

Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke
Upper limb impairment is a common debilitating consequence of ischemic stroke. Physical rehabilitation after stroke enhances neuroplasticity and improves limb function, but does not typically restore normal movement.
hodaparast NHays SASloan AMHulsey DRRuiz APantoja MRennaker RL 2ndKilgard MP

November 12, 2013

Increasing diversity of neural responses to speech sounds across the central auditory pathway
Neurons at higher stations of each sensory system are responsive to feature combinations not present at lower levels. As a result, the activity of these neurons becomes less redundant than lower levels.
Ranasinghe KGVrana WAMatney CJKilgard MP

November 6, 2013

Studies in RF Power Communication, SAR, and Temperature Elevation in Wireless Implantable Neural Interfaces
Implantable neural interfaces are designed to provide a high spatial and temporal precision control signal implementing high degree of freedom real-time prosthetic systems.
Yujuan Zhao, Lin Tang, Robert Rennaker, Chris Hutchens, Tamer S. Ibrahim

October 16, 2013

Similarity of Cortical Activity Patterns Predicts generalization Behavior
Humans and animals readily generalize previously learned knowledge to new situations. Determining similarity is critical for assigning category membership to a novel stimulus.
Crystal T. Engineer , Claudia A. Perez, Ryan S. Carraway, Kevin Q. Chang, Jarod L. Roland, Andrew M. Sloan, Michael P. Kilgard

October 7, 2013

Enabling energy efficient protocol processing for passive RFID sensors using sub/near-threshold circuit
Recent research trend of passive RFID based sensors has posed stringent low power requirement for energy efficient communication, which can be addressed by sub/near-Vt operation with standard CMOS process. This paper discusses new design challenges under scaled voltages and presents critical building blocks for low power protocol processing.
R. Liao, R. Ahmed, C. G. Hutchens, R. L. Rennaker

October 4, 2013

Investigating the structure and function of the retinohypothalamic tract in multiple sclerosis by optical coherence tomography (OCT) and pupillometry
Objective: To characterize the retinohypothalamic tract in the setting of multiple sclerosis and a history of optic neuritis by directly interrogating the functional output of the hypothalamus via body temperature, early morning melatonin suppression, and sleep, fatigue, and depression questionnaires.

August 7, 2013

Fear conditioning alters neuron-specific hippocampal place field stability via the basolateral amygdala
It is well established that physical changes to an environment result in plasticity of hippocampal place cell activity, while in the absence of changes, place fields are remarkably stable.
Donzis EJRennaker RLThompson LT

July 16, 2013

Impairment of cortical GABAergic synaptic transmission in an environmental rat model of autism
The biological mechanisms of autism spectrum disorders (ASDs) are largely unknown in spite of extensive research.
Banerjee AGarcía-Oscos FRoychowdhury SGalindo LCHall SKilgard MPAtzori M

July 16, 2013

Patent
Timing control for paired plasticity

July, 2013

Cortical speech-evoked response patterns in multiple auditory fields are correlated with behavioral discrimination ability
Different speech sounds evoke unique patterns of activity in primary auditory cortex (A1).
Centanni TMEngineer CTKilgard MP

July, 2013

A comparison of polymer substrates for photolithographic processing of flexible bioelectronics
Flexible bioelectronics encompass a new generation of sensing devices, in which controlled interactions with tissue enhance understanding of biological processes in vivo.
Dustin Simon, Taylor Ware, Ryan Marcotte, Benjamin R. Lund, Dennis W. Smith Jr., Matthew Di Prima, Robert L. Rennaker, Walter Voit

June 13, 2013

Rapid remission of conditioned fear expression with extinction training paired with vagus nerve stimulation
Fearful experiences can produce long-lasting and debilitating memories. Extinction of conditioned fear requires consolidation of new memories that compete with fearful associations.
Peña DF, Engineer ND, McIntyre CK

June 11, 2013

Mechanical cycling stability of organic thin film transistors on shape memory polymers
Organic thin film transistors on shape memory polymers are fabricated by full photolithography.
Avendano-Bolivar AWare TArreaga-Salas DSimon DVoit W

June, 2013

A Two Stage Power Optimized Implantable Neural Amplifier Based on Cascoded Structures
Hutchens, Chris, Renneker, Robert L, II

May 19, 2013

A 2μW digital baseband core for wireless Micro-Neural-Interface in 0.18μm CMOS
This paper presents the design of a low power digital baseband core with a custom-tailored protocol for wirelessly powered Micro-Neural-Interface (MNI) system on a chip (SoC) to be implanted within the skull to record cortical neural activities.
Ran Liao, Chriswell Hutchens, Robert. L. Rennaker

May 13, 2013

Thiol-ene/acrylate substrates for softening intracortical electrodes
Neural interfaces have traditionally been fabricated on rigid and planar substrates, including silicon and engineering thermoplastics.
Taylor Ware, Dustin Simon, Clive Liu, Tabassum Musa, Srikanth Vasudevan, Andrew Sloan, Edward W. Keefer, Robert L. Rennaker II, Walter Voit

March 30, 2013

The bradykinesia assessment task: An automated method to measure forelimb speed in rodents
Bradykinesia in upper extremities is associated with a wide variety of motor disorders; however, there are few tasks that assay forelimb movement speed in rodent models.
Seth A. Hays, Navid Khodaparast, Andrew M. Sloan, Tabbassum Fayyaz, Daniel R. Hulsey, Andrea D. Ruiz, Maritza Pantoja, Michael P. Kilgard, Robert L. Rennaker II

March, 2013

Different timescales for the neural coding of consonant and vowel sounds
Psychophysical, clinical, and imaging evidence suggests that consonant and vowel sounds have distinct neural representations. This study tests the hypothesis that consonant and vowel sounds are represented on different timescales within the same population of neurons by comparing behavioral discrimination with neural discrimination based on activity recorded in rat inferior colliculus and primary auditory cortex.
Perez CAEngineer CTJakkamsetti VCarraway RSPerry MSKilgard MP

February 8, 2013

Knockdown of the Dyslexia-Associated Gene Kiaa0319 Impairs Temporal Responses to Speech Stimuli in Rat Primary Auditory Cortex
One in 15 school age children have dyslexia, which is characterized by phoneme-processing problems and difficulty learning to read. Dyslexia is associated with mutations in the gene KIAA0319.
T. M. Centanni, A. B. Booker, A. M. Sloan, F. Chen, B. J. Maher, R. S. Carraway, N. Khodaparast, R. Rennaker, J. J. LoTurco and M. P. Kilgard

February 6, 2013

A target cell-specific role for presynaptic Fmr1 in regulating glutamate release onto neocortical fast-spiking inhibitory neurons
n the mouse model of Fragile X syndrome, the Fmr1 knock-out, local excitation of layer 4 fast-spiking (FS) inhibitory neurons is robustly decreased by 50%, but the mechanisms mediating this change are unknown. Here, we performed recordings in acutely prepared slices obtained from Fmr1 "mosaic" mice, where Fmr1 is deleted in about half of all neurons, and we found that loss of presynaptic, but not postsynaptic, Fmr1 fully recapitulates the deficit.
Patel ABHays SABureau IHuber KMGibson JR

February 4, 2013

Smart Polymers for Neural Interfaces
Thermomechanical properties of smart polymers can be specifically tuned to address critical problems in neural interfaces. A compilation of materials and approaches is presented from each of three often overlapping research communities: shape memory polymers, hydrogels, and neural interfaces.
Taylor Ware, Dustin Simon, Robert L. Rennaker II & Walter Voit

January 30, 2013

The isometric pull task: A novel automated method for quantifying forelimb force generation in rats
Reach-to-grasp tasks are commonly used to assess forelimb function in rodent models. While these tasks have been useful for investigating several facets of forelimb function, they are typically labor-intensive and do not directly quantify physiological parameters.
Seth A. Hays, Navid Khodaparast, Andrew M. Sloan, Daniel R. Hulsey, Maritza Pantoja, Andrea D. Ruiz, Michael P. Kilgard, Robert L. Rennaker II

January 28, 2013

Sub-meninges implantation reduces immune response to neural implants
One in 15 school age children have dyslexia, which is characterized by phoneme-processing problems and difficulty learning to read. Dyslexia is associated with mutations in the gene KIAA0319.
Neil T. Markwardt, Jodi Stokol, Robert L. Rennaker II

January 2013

Directing neural plasticity to understand and treat tinnitus
The functional organization of cortical and subcortical networks can be altered by sensory experience. Sensory deprivation destabilizes neural networks resulting in increased excitability, greater neural synchronization and increased spontaneous firing in cortical and subcortical neurons.
Navzer D. Engineer, Aage R. Møller, Michael P. Kilgard

2012

December 2012

Harnessing plasticity to understand learning and treat disease
A large body of evidence suggests that neural plasticity contributes to learning and disease. Recent studies suggest that cortical map plasticity is typically a transient phase that improves learning by increasing the pool of task-relevant responses.

November 20, 2012

Three-Dimensional Flexible Electronics Enabled by Shape Memory Polymer Substrates for Responsive Neural Interfaces
Planar electronics processing methods have enabled neural interfaces to become more precise and deliver more information. However, this processing paradigm is inherently 2D and rigid.

August 13, 2012

Neural mechanisms supporting robust discrimination of spectrally and temporally degraded speech
Cochlear implants provide good speech discrimination ability despite highly limited amount of information they transmit compared with normal cochlea.

July 28, 2012

Experience-Dependent Plasticity and Auditory Cortex
Throughout their lifetimes, individuals are constantly engaged by acoustic environments that leave lasting impressions, such as the sound of a familiar voice or the rhythm of a catchy tune. A fundamental question in auditory neuroscience concerns how and where such acoustic knowledge is acquired and stored in the brain.
Kathryn N. Shepard, Michael P. Kilgard, Robert C. Liu

July 2012

Speech discrimination after early exposure to pulsed-noise or speech
Early experience of structured inputs and complex sound features generate lasting changes in tonotopy and receptive field properties of primary auditory cortex (A1).

May 2, 2012

Fabrication of Responsive, Softening Neural Interfaces
A novel processing method is described using photolithography to pattern thin-film flexible electronics on shape memory polymer substrates with mechanical properties tailored to improve biocompatability and enhance adhesion between the polymer substrate and metal layers.

February 21, 2012

Complex Mixture Discrimination and the Role of Contaminants
Rats were trained in a 2-alternative odor choice task to discriminate between a 10-component odor mixture and the same mixture with one component removed and replaced with 1 of 3 concentrations of a different monomolecular odor (contaminant).

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