Browsing by Author "Rennaker, Robert L."
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Item A Suite of Automated Tools to Quantify Hand and Wrist Motor Function after Cervical Spinal Cord Injury(BioMed Central Ltd.) Grasse, Katelyn M.; Hays, Seth A.; Rahebi, Kimiya C.; Warren, Victoria S.; Garcia, Elizabeth A.; Wigginton, Jane G.; Kilgardi Mchael P.; Rennaker, Robert L.; 0000-0003-4225-241X (Hays, SA); 13146094343400332984 (Hays, SA); Grasse, Katelyn M.; Hays, Seth A.; Rahebi, Kimiya C.; Warren, Victoria S.; Garcia, Elizabeth A.; Wigginton, Jane G.; Kilgard, Michael P.; Rennaker, Robert L.Background: Cervical spinal cord injury (cSCI) often causes chronic upper extremity disability. Reliable measurement of arm function is critical for development of therapies to improve recovery after cSCI. In this study, we report a suite of automated rehabilitative tools to allow simple, quantitative assessment of hand and wrist motor function. Methods: We measured range of motion and force production using these devices in cSCI participants with a range of upper limb disability and in neurologically intact participants at two time points separated by approximately 4 months. Additionally, we determined whether measures collected with the rehabilitative tools correlated with standard upper limb assessments, including the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) and the Jebsen Hand Function Test (JHFT). Results: We find that the rehabilitative devices are useful to provide assessment of upper limb function in physical units over time in SCI participants and are well-correlated with standard assessments. Conclusions: These results indicate that these tools represent a reliable system for longitudinal evaluation of upper extremity function after cSCI and may provide a framework to assess the efficacy of strategies aimed at improving recovery of upper limb function. ©2019 The Author(s).Item Effects of Vagus Nerve Stimulation on Extinction of Conditioned Fear and Post-Traumatic Stress Disorder Symptoms in RatsNoble, Lindsey J.; Gonzalez, I. J.; Meruva, V. B.; Callahan, Kathleen A.; Belfort, Benjamin D.; Ramanathan, K. R.; Meyers, Eric; Kilgard, Michael P.; Rennaker, Robert L.; McIntyre, Christa K.; Noble, Lindsey J.; Gonzalez, I. J.; Meruva, V. B.; Callahan, Kathleen A.; Belfort, Benjamin D.; Ramanathan, K. R.; Meyers, Eric; Kilgard, Michael P.; Rennaker, Robert L.; McIntyre, Christa K.Exposure-based therapies help patients with post-traumatic stress disorder (PTSD) to extinguish conditioned fear of trauma reminders. However, controlled laboratory studies indicate that PTSD patients do not extinguish conditioned fear as well as healthy controls, and exposure therapy has high failure and dropout rates. The present study examined whether vagus nerve stimulation (VNS) augments extinction of conditioned fear and attenuates PTSD-like symptoms in an animal model of PTSD. To model PTSD, rats were subjected to a single prolonged stress (SPS) protocol, which consisted of restraint, forced swim, loss of consciousness, and 1 week of social isolation. Like PTSD patients, rats subjected to SPS show impaired extinction of conditioned fear. The SPS procedure was followed, 1 week later, by auditory fear conditioning (AFC) and extinction. VNS or sham stimulation was administered during half of the extinction days, and was paired with presentations of the conditioned stimulus. One week after completion of extinction training, rats were given a battery of behavioral tests to assess anxiety, arousal and avoidance. Results indicated that rats given SPS 1 week prior to AFC (PTSD model) failed to extinguish the freezing response after eleven consecutive days of extinction. Administration of VNS reversed the extinction impairment and attenuated reinstatement of the conditioned fear response. Delivery of VNS during extinction also eliminated the PTSD-like symptoms, such as anxiety, hyperarousal and social avoidance for more than 1 week after VNS treatment. These results provide evidence that extinction paired with VNS treatment can lead to remission of fear and improvements in PTSD-like symptoms. Taken together, these findings suggest that VNS may be an effective adjunct to exposure therapy for the treatment of PTSD.Item Enhancing Plasticity in Central Networks Improves Motor and Sensory Recovery after Nerve Damage(Springer Nature, 2019-12-19) Meyers, Eric C.; Kasliwal, Nimit; Solorzano, Bleyda R.; Lai, Elaine; Bendale, Geetanjali; Berry, Abigail; Ganzer, Patrick D.; Romero-Ortega, Mario; Rennaker, Robert L.; Kilgard, Michael P.; Hays, Seth A.; 0000-0002-2013-5450 (Meyers, EC); 0000-0001-6314-9062 (Kasliwal, N); 0000-0003-2576-2629 (Romero-Ortega, M); 0000-0003-4225-241X (Hays, SA); Meyers, Eric C.; Kasliwal, Nimit; Solorzano, Bleyda R.; Lai, Elaine; Bendale, Geetanjali; Berry, Abigail; Ganzer, Patrick D.; Romero-Ortega, Mario; Rennaker, Robert L.; Kilgard, Michael P.; Hays, Seth A.Nerve damage can cause chronic, debilitating problems including loss of motor control and paresthesia, and generates maladaptive neuroplasticity as central networks attempt to compensate for the loss of peripheral connectivity. However, it remains unclear if this is a critical feature responsible for the expression of symptoms. Here, we use brief bursts of closed-loop vagus nerve stimulation (CL-VNS) delivered during rehabilitation to reverse the aberrant central plasticity resulting from forelimb nerve transection. CL-VNS therapy drives extensive synaptic reorganization in central networks paralleled by improved sensorimotor recovery without any observable changes in the nerve or muscle. Depleting cortical acetylcholine blocks the plasticity-enhancing effects of CL-VNS and consequently eliminates recovery, indicating a critical role for brain circuits in recovery. These findings demonstrate that manipulations to enhance central plasticity can improve sensorimotor recovery and define CL-VNS as a readily translatable therapy to restore function after nerve damage.Item Pairing Sound with Vagus Nerve Stimulation Modulates Cortical Synchrony and Phase Coherence in Tinnitus: An Exploratory Retrospective Study(Nature Publishing Group) Vanneste, Sven; Martin, Jeffrey S.; Rennaker, Robert L.; Kilgard, Michael P.; 0000 0001 2879 2132 (Rennaker, RL); 0000 0001 3852 473X (Kilgard, MP); 0000-0002-9906-1836 (Vanneste, S); Vanneste, Sven; Martin, Jeffrey S.; Rennaker, Robert L.; Kilgard, Michael P.Recent research has shown that vagus nerve stimulation (VNS) paired with tones or with rehabilitative training can help patients to achieve reductions in tinnitus perception or to expedite motor rehabilitation after suffering an ischemic stroke. The rationale behind this treatment is that VNS paired with experience can drive neural plasticity in a controlled and therapeutic direction. Since previous studies observed that gamma activity in the auditory cortex is correlated with tinnitus loudness, we assessed resting-state source-localized EEG before and after one to three months of VNS-tone pairing in chronic tinnitus patients. VNS-tone pairing reduced gamma band activity in left auditory cortex. VNStone pairing also reduced the phase coherence between the auditory cortex and areas associated with tinnitus distress, including the cingulate cortex. These results support the hypothesis that VNS-tone pairing can direct therapeutic neural plasticity. Targeted plasticity therapy might also be adapted to treat other conditions characterized by hypersynchronous neural activity.Item Speech Sound Processing Deficits and Training-Induced Neural Plasticity in Rats with Dyslexia Gene Knockdown(Public Library of Science) Centanni, Tracy M.; Chen, Fuyi; Booker, Anne M.; Engineer, Crystal T.; Sloan, Andrew M.; Rennaker, Robert L.; LoTurco, Joseph J.; Kilgard, Michael P.; 0000 0001 3852 473X (Kilgard, MP); 0000 0001 2879 2132 (Rennaker, RL)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. We tested the hypothesis that KIA- rats would be impaired at speech sound discrimination. KIA- rats needed twice as much training in quiet conditions to perform at control levels and remained impaired at several speech tasks. Focused training using truncated speech sounds was able to normalize speech discrimination in quiet and background noise conditions. Training also normalized trial-by-trial neural variability and temporal phase locking. Cortical activity from speech trained KIA- rats was sufficient to accurately discriminate between similar consonant sounds. These results provide the first direct evidence that assumed reduced expression of the dyslexia-associated gene KIAA0319 can cause phoneme processing impairments similar to those seen in dyslexia and that intensive behavioral therapy can eliminate these impairments. ;Item Vagus Nerve Stimulation and Rehabilitation Improves Recovery of a Motor Task after Neurological Injury(2015-06-25) Choi, Rachel; Meyers, Eric; Ganzer, Patrick; Hays, Seth; Kilgard, Michael P.; Rennaker, Robert L.; 0000 0001 3852 473X (Kilgard, MP); 0000 0001 2879 2132 (Rennaker, RL)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. Sprague-Dawley rats affected by a spinal cord contusion at C5 and administered VNS paired with rehabilitation exhibited significant recovery of forelimb strength on an isometric pull task. We also propose similar recovery of supination function in Sprague-Dawley rats affected by endothelin-1‐induced focal motor cortex ischemic stroke. Thus, VNS paired with rehabilitation may be an effective therapeutic tool in the event of neurological injury such as ischemic stroke or spinal cord injury.Item Vagus Nerve Stimulation Promotes Generalization of Conditioned Fear Extinction and Reduces Anxiety in Rats(Elsevier Science Inc, 2018-09-21) Noble, Lindsey J.; Meruva, Venkat B.; Hays, Seth A.; Rennaker, Robert L.; Kilgard, Michael P.; McIntyre, Christa K.; 0000-0003-4225-241X (Hays, SA); 13146094343400332984 (Hays, SA); Noble, Lindsey J.; Meruva, Venkat B.; Hays, Seth A.; Rennaker, Robert L.; Kilgard, Michael P.; McIntyre, Christa K.Background: Exposure-based therapies are used to treat a variety of trauma- and anxiety-related disorders by generating successful extinction following cue exposure during treatment. The development of adjuvant strategies that accelerate extinction learning, improve tolerability, and increase efficiency of treatment could increase the efficacy of exposure-based therapies. Vagus nerve stimulation (VNS) paired with exposure can enhance fear extinction, in rat models of psychiatric disorders, and chronic administration of VNS reduces anxiety in rats and humans. Objective: We tested whether VNS, like other cognitive enhancers, could produce generalization of extinction for stimuli that are not presented during the extinction sessions, but are associated with the fear event. Methods: Male Sprague Dawley rats underwent auditory fear conditioning with two easily discriminable auditory stimuli. Following fear conditioning, extinction training consisted of exposure to only one of the conditioned sounds. Half of the rats received VNS and half received sham stimulation during with sound presentations. VNS effects on anxiety were examined in a separate study where VNS was administered prior to testing on the elevated plus maze. Results: Sham stimulated rats given 20 presentations of a conditioned stimulus (CS) during the extinction session showed performance that was matched to VNS-treated rats given only 4 presentations of the CS. Despite comparable levels of freezing to the presented CS, only the VNS-treated rats showed a significant decrease in freezing to the CS that was not presented. VNS-induced generalization of extinction was observed only when the two sounds were paired with footshock within the same fear conditioning session; VNS did not promote generalization of extinction when the two sounds were conditioned on different days or in different contexts. On the anxiety test, VNS administration significantly increased time spent in the open arms of the elevated plus maze. Conclusion: These results provide evidence that VNS can promote generalization of extinction to other stimuli associated with a specific fear experience. Furthermore, non-contingent VNS appears to reduce anxiety. The ability to generalize extinction and reduce anxiety makes VNS a potential candidate for use as an adjunctive strategy to improve the efficacy and tolerability of exposure-based therapies.Item Vagus Nerve Stimulation Reverses the Extinction Impairments in a Model of PTSD with Prolonged and Repeated Trauma(Taylor and Francis Ltd, 2019-04-23) Souza, Rimenez R.; Robertson, Nicole M.; Pruitt, David T.; Gonzales, Phillip A.; Hays, Seth A.; Rennaker, Robert L.; Kilgard, Michael P.; McIntyre, Crista K.; 0000-0003-4225-241X (Hays, SA); 13146094343400332984 (Hays, SA); Souza, Rimenez R.; Robertson, Nicole M.; Pruitt, David T.; Gonzales, Phillip A.; Hays, Seth A.; Rennaker, Robert L.; Kilgard, Michael P.; McIntyre, Crista K.We have shown that vagus nerve stimulation (VNS) enhances extinction of conditioned fear and reduces anxiety in rat models of PTSD using moderate stress. However, it is still unclear if VNS can be effective in enhancing extinction of severe fear after prolonged and repeated trauma. Severe fear was induced in adult male rats by combining single prolonged stress (SPS) and protracted aversive conditioning (PAC). After SPS and PAC procedures, rats were implanted with stimulating cuff electrodes, exposed to five days of extinction training with or without VNS, and then tested for extinction retention, return of fear in a new context and reinstatement. The elevated plus maze, open field and startle were used to test anxiety. Sham rats showed no reduction of fear during extensive extinction training. VNS-paired with extinction training reduced freezing at the last extinction session by 70% compared to sham rats. VNS rats exhibited half as much fear as shams, as well as less fear renewal. Sham rats exhibited significantly more anxiety than naive controls, whereas VNS rats did not. These results demonstrate that VNS enhances extinction and reduces anxiety in a severe model of PTSD that combined SPS and a conditioning procedure that is 30 times more intense than the conditioning procedures in previous VNS studies. The broad utility of VNS in enhancing extinction learning in rats and the strong clinical safety record of VNS suggest that VNS holds promise as an adjuvant to exposure-based therapy in people with PTSD and other complex forms of this condition. ©2019 Informa UK Limited, trading as Taylor & Francis Group.Item A Within-Animal Comparison of Skilled Forelimb Assessments in Rats(Public Library of Science) Sloan, Andrew M.; Fink, Melyssa K.; Rodriguez, Amber J.; Lovitz, Adam M.; Khodaparast, Navid; Rennaker, Robert L.; Hays, Seth A.; 0000 0001 2879 2132 (Rennaker, RL)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. Here, we provide a within-subject comparison of three common forelimb assessments to allow direct evaluation of sensitivity and efficiency across tasks. Rats were trained to perform the single pellet skilled reaching task, the pasta matrix task, and the isometric pull task. Once proficient on all three tasks, rats received an ischemic lesion of motor cortex and striatum to impair use of the trained limb. On the second week post-lesion, all three tasks measured a significant deficit in forelimb function. Performance was well-correlated across tasks. By the sixth week post-lesion, only the isometric pull task measured a significant deficit in forelimb function, suggesting that this task is more sensitive to chronic impairments. The number of training days required to reach asymptotic performance was longer for the isometric pull task, but the total experimenter time required to collect and analyze data was substantially lower. These findings suggest that the isometric pull task represents an efficient, sensitive measure of forelimb function to facilitate preclinical evaluation in models of neurological injury and disease.