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m Glu5 is less associated with its scaffolding protein Homer in Fmr1 KO mice, and restoration of m Glu5-Homer interactions by genetic deletion of a short, dominant negative of Homer, H1a, rescues many phenotypes of Fmr1 KO mice. We recently described a stress-induced interleukin-6 dependent mechanism leading to a decrease in s I/E in the rodent temporal cortex. Rennaker, II; 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. Guo W, Molinaro G, Collins KA, Hays SA, Paylor R, Worley PF, Szumlinski KK, Huber KM 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. Kilgard 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 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. Apart from these core symptoms, a significant number of ASD individuals display higher levels of anxiety and some ASD individuals exhibit impaired emotional learning.
Varying the pulse frequency substantially affects the timing, but not the total amount, of phasic LC activity. Pruitt DT, Schmid AN, Kim LJ, Abe CM, Trieu JL, Choua C, Hays SA, Kilgard MP, Rennaker RL 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. De Ridder D, Kilgard M, Engineer N, Vanneste S Vagus Nerve Stimulation Improves Motor Function After Chronic Stroke in Adult Rats Stroke is the leading cause of serious long-term disability. Xiaoqing Zhu, Fang Wang, Huifang Hu, Xinde Sun, Michael P. Merzenich, and Xiaoming Zhou 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. Michael Kilgard 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. 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. Many activities of daily living, however, require consistent application of controlled submaximal force rather than maximal force. Kilgard 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. hodaparast N, Hays SA, Sloan AM, Hulsey DR, Ruiz A, Pantoja M, Rennaker RL 2nd, Kilgard MP 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. This paper discusses new design challenges under scaled voltages and presents critical building blocks for low power protocol processing. Dustin Simon, Taylor Ware, Ryan Marcotte, Benjamin R. Extinction of conditioned fear requires consolidation of new memories that compete with fearful associations. Dyslexia is associated with mutations in the gene KIAA0319. Hays, Seth A.; Khodaparast, Navid; Ruiz, Andrea; Sloan, Andrew M.; Hulsey, Daniel R.; Rennaker, Robert L. 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. Physical rehabilitation after stroke enhances neuroplasticity and improves limb function, but does not typically restore normal movement. Kilgard 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. Centanni TM, Engineer CT, Kilgard MP 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. Rennaker, Walter Voit Rapid remission of conditioned fear expression with extinction training paired with vagus nerve stimulation Fearful experiences can produce long-lasting and debilitating memories. Perez CA, Engineer CT, Jakkamsetti V, Carraway RS, Perry MS, Kilgard MP 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.
Kilgard Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke Upper limb impairment is a common debilitating consequence of ischemic stroke. Banerjee A, García-Oscos F, Roychowdhury S, Galindo LC, Hall S, Kilgard MP, Atzori M Patent Timing control for paired plasticity 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). 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.
The majority of injuries occur in the upper extremities, and functional recovery is often limited. 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. John, Sakthi Rajendran, Tong Kang, Radu Reit, David Arreaga-Salas, Daniel G. Our recent studies demonstrate that vagus nerve stimulation (VNS) paired with rehabilitative training improves recovery of function in multiple models of stroke. Frohman, Nathaniel Lizak, Jayne Lim, Scott Kolbe, Robert L. While the neighboring auditory cortical fields each contain information about speech sound identity, each field processes speech sounds differently. Kilgard 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. Determining similarity is critical for assigning category membership to a novel stimulus.
Kilgard Patent Methods, systems, and devices for pairing vagus nerve stimulation with motor therapy in stroke patients 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. A major limitation of existing intracortical probe technology pertains to limited lifetime of 6 months to a year of recording after implantation. Currently, there are no consistently effective rehabilitative treatments for chronic stroke patients. Joanne Fielding, Meaghan Clough, Shin Beh, Lynette Millist, Derek Sears, Ashley N. Extensive speech sound discrimination training alters A1 responses. Ibrahim Similarity of Cortical Activity Patterns Predicts generalization Behavior Humans and animals readily generalize previously learned knowledge to new situations.
Voit Forelimb training drives transient map reorganization in ipsilateral motor cortex Skilled motor training results in reorganization of contralateral motor cortex movement representations. As a result, the activity of these neurons becomes less redundant than lower levels. Peña DF, Engineer ND, Mc Intyre CK 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. Rennaker Thiol-ene/acrylate substrates for softening intracortical electrodes Neural interfaces have traditionally been fabricated on rigid and planar substrates, including silicon and engineering thermoplastics.
Rehabilitative therapies aim to promote adaptive circuit changes after neurological disease or injury, but insufficient or maladaptive plasticity often prevents a full recovery. Optical coherence tomography (OCT) has been shown to be a sensitive, and precise method of quantifying structural retinal changes that occur in MS. We have developed a method using vagus nerve stimulation (VNS) paired with motor training to drive robust, specific plasticity in the motor cortex. De Ridder D, Vanneste S, Engineer ND, Kilgard MP 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.
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. Hays 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. Hays SA, Ruiz A, Bethea T, Khodaparast N, Carmel JB, Rennaker RL 2nd, Kilgard MP 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. 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 CT, Centanni TM, Im KW, Borland MS, Moreno NA, Carraway RS, Wilson LG, Kilgard MP Neural Coding of Speech Sounds Speech sounds are composed of both rapid spectrotemporal changes and slow steady-state portions. We have developed a rehabilitation intervention to address this issue. 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.