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1. A blended neurostimulation protocol to delineate cortico-muscular and spino-muscular dynamics following neuroplastic adaptation

   https://doi.org/10.3389/fneur.2023.1114860  

   Stefanovic, Filip ; Martinez, Julian A. ; Saleem, Ghazala T. ; Sisto, Sue Ann ; Miller, Michael T. ; Achampong, Yaa A. ; Titus, Albert H. ( June 2023 , Frontiers in Neurology)

   In this paper we propose a novel neurostimulation protocol that provides an intervention-based assessment to distinguish the contributions of different motor control networks in the cortico-spinal system. Specifically, we use a combination of non-invasive brain stimulation and neuromuscular stimulation to probe neuromuscular system behavior with targeted impulse-response system identification. In this protocol, we use an in-house developed human-machine interface (HMI) for an isotonic wrist movement task, where the user controls a cursor on-screen. During the task, we generate unique motor evoked potentials based on triggered cortical or spinal level perturbations. Externally applied brain-level perturbations are triggered through TMS to cause wrist flexion/extension during the volitional task. The resultant contraction output and related reflex responses are measured by the HMI. These movements also include neuromodulation in the excitability of the brain-muscle pathway via transcranial direct current stimulation. Colloquially, spinal-level perturbations are triggered through skin-surface neuromuscular stimulation of the wrist muscles. The resultant brain-muscle and spinal-muscle pathways perturbed by the TMS and NMES, respectively, demonstrate temporal and spatial differences as manifested through the human-machine interface. This then provides a template to measure the specific neural outcomes of the movement tasks, and in decoding differences in the contribution of cortical- (long-latency) and spinal-level (short-latency) motor control. This protocol is part of the development of a diagnostic tool that can be used to better understand how interaction between cortical and spinal motor centers changes with learning, or injury such as that experienced following stroke.

    

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2. Effect of spinal cord injury on neural encoding of spontaneous postural perturbations in the hindlimb sensorimotor cortex

   Jaimie B Dougherty ( January 2021 , Journal of neurophysiology)

   Capers, Miriam (Ed.)

   Supraspinal signals play a significant role in compensatory responses to postural perturbations after spinal cord injury (SCI). SCI disrupts descending motor control signals as well as ascending somatosensory information to and from below the lesion. In intact animals, While cortical signals are not necessary for basic postural tasks, but neurons in the motor cortex have been shown to respond to periodic postural perturbations in intact animals. However, the role of the cortex in postural control after spinal cord injury in response to unexpected postural perturbations has not been studied. To better understand how spinal lesions impact cortical encoding of information about unexpected postural perturbations, the activity of single neurons in the rat hindlimb sensorimotor cortex (HLSMC) were recorded during unexpected tilts before and after a complete midthoracic spinal transection. In a subset of animals, limb ground reaction forces were collected as well. Results show that responses in the HLSMC were modulated with changes in tilt severity (i.e. tilt velocity). As initial velocity of the tilt increased, more information was conveyed by the HLSMC neurons about the perturbation due to increases in both the number of recruited neurons and the magnitude of their response. After SCI hindlimb ground reaction forces were both attenuated and delayed, and the neural responses were delayed and less likely to respond to slower tilts. This resulted in a moderate decrease inan attenuation of the information conveyed by cortical neurons about the tilts, requiring more cells to convey the same amount of information as before the transection. Given that reorganization of the hindlimb sensorimotor cortex in response to therapy after complete mid-thoracic SCI is necessary for behavioral recovery, this sustained encoding of information after SCI could be a substrate for the reorganization that uses sensory information from above the lesion to control trunk muscles that permit weight-supported stepping and postural control. 

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3. Restoring Function After Severe Spinal Cord Injury Through BioLuminescent-OptoGenetics

   https://doi.org/10.3389/fneur.2021.792643  

   Petersen, Eric D. ; Sharkey, Erik D. ; Pal, Akash ; Shafau, Lateef O. ; Zenchak-Petersen, Jessica ; Peña, Alex J. ; Aggarwal, Anu ; Prakash, Mansi ; Hochgeschwender, Ute ( January 2022 , Frontiers in Neurology)

   The ability to manipulate specific neuronal populations of the spinal cord following spinal cord injury (SCI) could prove highly beneficial for rehabilitation in patients through maintaining and strengthening still existing neuronal connections and/or facilitating the formation of new connections. A non-invasive and highly specific approach to neuronal stimulation is bioluminescent-optogenetics (BL-OG), where genetically expressed light emitting luciferases are tethered to light sensitive channelrhodopsins (luminopsins, LMO); neurons are activated by the addition of the luciferase substrate coelenterazine (CTZ). This approach utilizes ion channels for current conduction while activating the channels through the application of a small chemical compound, thus allowing non-invasive stimulation and recruitment of all targeted neurons. Rats were transduced in the lumbar spinal cord with AAV2/9 to express the excitatory LMO3 under control of a pan-neuronal or motor neuron-specific promoter. A day after contusion injury of the thoracic spine, rats received either CTZ or vehicle every other day for 2 weeks. Activation of either neuron population below the level of injury significantly improved locomotor recovery lasting beyond the treatment window. Utilizing histological and gene expression methods we identified neuronal plasticity as a likely mechanism underlying the functional recovery. These findings provide a foundation for a rational approach to spinal cord injury rehabilitation, thereby advancing approaches for functional recovery after SCI. Summary Bioluminescent optogenetic activation of spinal neurons results in accelerated and enhanced locomotor recovery after spinal cord injury in rats. 

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4. 66361 TL1 Team Approach to Predicting Response to Spinal Cord Stimulation for Chronic Low Back Pain

   https://doi.org/10.1017/cts.2021.685  

   See, Kyle ; Ho, Rachel ; Coombes, Stephen ; Fang, Ruogu ( March 2021 , Journal of Clinical and Translational Science)

   ABSTRACT IMPACT: Understanding how spinal cord stimulation works and who it works best for will improve clinical trial efficacy and prevent unnecessary surgeries. OBJECTIVES/GOALS: Spinal cord stimulation (SCS) is an intervention for chronic low back pain where standard interventions fail to provide relief. However, estimates suggest only 58% of patients achieve at least 50% reduction in their pain. There is no non-invasive method for predicting relief provided by SCS. We hypothesize neural activity in the brain can fill this gap. METHODS/STUDY POPULATION: We tested SCS patients at 3 times points: baseline (pre-surgery), at day 7 during the trial period (post-trial), and 6 months after a permanent system had been implanted. At each time point participants completed 10 minutes of eyes closed, resting electroencephalography (EEG) and self-reported their pain. EEG was collected with the ActiveTwo system and a 128-electrode cap. Patients were grouped based on the percentage change of their pain from baseline to the final visit using a median split (super responders > average responders). Spectral density powerbands were extracted from resting EEG to use as input features for machine learning analyses. We used support vector machines to predict response to SCS. RESULTS/ANTICIPATED RESULTS: Baseline and post-trial EEG data predicted SCS response at 6-months with 95.56% and 100% accuracy, respectively. The gamma band had the highest performance in differentiating responders. Post-trial EEG data best differentiated the groups with feature weighted dipoles being more highly localized in sensorimotor cortex. DISCUSSION/SIGNIFICANCE OF FINDINGS: Understanding how SCS works and who it works best for is the long-term objective of our collaborative research program. These data provide an important first step towards this goal. 

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5. Kapton Polyimide-Based EEG Microelectrode Array and Interfaces for Mice Brainwave Recordings and Analysis

   https://doi.org/DOI: 10.1117/12.2305145  

   D. Gupta, M. Islama ( April 2018 , Proc. SPIE 10662, Smart Biomedical and Physiological Sensor Technology XV 106620D)

   There is a rise in the study of functional connectivity among various cortical regions and investigations to uncover causal links between a stimulus and the corresponding neural dynamics through electrophysiological imaging of the human brain. Animal model that exhibit simplistic representations of such networks open a doorway for such investigations and are gaining rapid popularity. In this study, we investigate and compare resting state network and auditory stimulus related activity with minimal invasive technology along computational spectral analysis on a C57/BL6 based mouse model. Somatosensory, motor and visual cortex are observed to be highly active and significantly correlated (p-value<0.05). Moreover, given the spatial limitation due to small size of the mouse head, we also describe a low-cost and effective fabrication process for the mouse EEG Polyimide Based Microelectrodes (PBM) array. The easy-to-implement fabrication process involves transfer of the pattern on a copper layer of the Kapton film followed by gold electroplating and application of insulation paint. Acoustic stimulation is done by using tube extensions for avoiding electrical coupling to EEG signals. Unlike multi-electrode array type of invasive methods that are local to a cortical region, the methods established in this study can be used for examining functional connectivity analysis, neural dynamics and cortical response at a global level. 

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