An official website of the United States government
Abstract Objective. Transcutaneous spinal cord stimulation (TSS) has been shown to be a promising non-invasive alternative to epidural spinal cord stimulation for improving outcomes of people with spinal cord injury (SCI). However, studies on the effects of TSS on cortical activation are limited. Our objectives were to evaluate the spatiotemporal effects of TSS on brain activity, and determine changes in functional connectivity under several different stimulation conditions. As a control, we also assessed the effects of functional electrical stimulation (FES) on cortical activity. Approach . Non-invasive scalp electroencephalography (EEG) was recorded during TSS or FES while five neurologically intact participants performed one of three lower-limb tasks while in the supine position: (1) A no contraction control task, (2) a rhythmic contraction task, or (3) a tonic contraction task. After EEG denoising and segmentation, independent components (ICs) were clustered across subjects to characterize sensorimotor networks in the time and frequency domains. ICs of the event related potentials (ERPs) were calculated for each cluster and condition. Next, a Generalized Partial Directed Coherence (gPDC) analysis was performed on each cluster to compare the functional connectivity between conditions and tasks. Main results . IC analysis of EEG during TSS resulted in three clusters identified at Brodmann areas (BA) 9, BA 6, and BA 4, which are areas associated with working memory, planning, and movement control. Lastly, we found significant ( p < 0.05, adjusted for multiple comparisons) increases and decreases in functional connectivity of clusters during TSS, but not during FES when compared to the no stimulation conditions. Significance. The findings from this study provide evidence of how TSS recruits cortical networks during tonic and rhythmic lower limb movements. These results have implications for the development of spinal cord-based computer interfaces, and the design of neural stimulation devices for the treatment of pain and sensorimotor deficit.
more »
« less
Constructing 2D maps of human spinal cord activity and isolating the functional midline with high-density microelectrode arrays
A roadmap of the spine During spinal cord surgery, intraoperative neuromonitoring (IONM) is used to reduce the risk of damage. Electrodes on muscles or scalp record the response to large-amplitude electrical stimuli delivered to the spinal cord. However, this method does not allow precise spatiotemporal characterization of spinal cord neurophysiology. Now, Russman et al. developed a microelectrode array that can be placed on the spinal cord during surgery and record with high spatiotemporal definition and high sensitivity the electrophysiological response to low-current stimulation, providing precise maps of spinal cord electrophysiology. These maps can be used during surgery to improve IONM.
more »
« less
- Award ID(s):
- 1728497
- PAR ID:
- 10392409
- Date Published:
- Journal Name:
- Science Translational Medicine
- Volume:
- 14
- Issue:
- 664
- ISSN:
- 1946-6234
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Martin, Allan R. (Ed.)Cellular differentiation is a tightly regulated process under the control of intricate signaling and transcription factors interaction network working in coordination. These interactions make the systems dynamic, robust and stable but also difficult to dissect. In the spinal cord, recent work has shown that a network of FGF, WNT and Retinoic Acid (RA) signaling factors regulate neural maturation by directing the activity of a transcription factor network that contains CDX at its core. Here we have used partial and ordinary (Hill) differential equation based models to understand the spatiotemporal dynamics of the FGF/WNT/RA and the CDX/transcription factor networks, alone and in combination. We show that in both networks, the strength of interaction among network partners impacts the dynamics, behavior and output of the system. In the signaling network, interaction strength determine the position and size of discrete regions of cell differentiation and small changes in the strength of the interactions among networking partners can result in a signal overriding, balancing or oscillating with another signal. We also show that the spatiotemporal information generated by the signaling network can be conveyed to the CDX/transcription network to produces a transition zone that separates regions of high cell potency from regions of cell differentiation, in agreement with most in vivo observations. Importantly, one emerging property of the networks is their robustness to extrinsic disturbances, which allows the system to retain or canalize NP cells in developmental trajectories. This analysis provides a model for the interaction conditions underlying spinal cord cell maturation during embryonic axial elongation.more » « less
-
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.more » « less
-
null (Ed.)Inducing regeneration in injured spinal cord represents one of modern medicine’s greatest challenges. Research from a variety of model organisms indicates that Hedgehog (Hh) signaling may be a useful target to drive regeneration. However, the mechanisms of Hh signaling-mediated tissue regeneration remain unclear. Here, we examined Hh signaling during post-amputation tail regeneration in Xenopus laevis larvae. We found that while Smoothened (Smo) activity is essential for proper spinal cord and skeletal muscle regeneration, transcriptional activity of the canonical Hh effector Gli is repressed immediately following amputation, and inhibition of Gli1/2 expression or transcriptional activity has minimal effects on regeneration. In contrast, we demonstrate that protein kinase A is necessary for regeneration of both muscle and spinal cord, in concert with and independent of Smo, respectively, and that its downstream effector CREB is activated in spinal cord following amputation in a Smo-dependent manner. Our findings indicate that non-canonical mechanisms of Hh signaling are necessary for spinal cord and muscle regeneration.more » « less
-
null (Ed.)Neutrophils are short-lived cells of the innate immune system and the first line of defense at the site of an infection and tissue injury. Pattern recognition receptors on neutrophils recognize pathogen-associated molecular patterns or danger-associated molecular patterns, which recruit them to the destined site. Neutrophils are professional phagocytes with efficient granular constituents that aid in the neutralization of pathogens. In addition to phagocytosis and degranulation, neutrophils are proficient in creating neutrophil extracellular traps (NETs) that immobilize pathogens to prevent their spread. Because of the cytotoxicity of the associated granular proteins within NETs, the microbes can be directly killed once immobilized by the NETs. The role of neutrophils in infection is well studied; however, there is less emphasis placed on the role of neutrophils in tissue injury, such as traumatic spinal cord injury. Upon the initial mechanical injury, the innate immune system is activated in response to the molecules produced by the resident cells of the injured spinal cord initiating the inflammatory cascade. This review provides an overview of the essential role of neutrophils and explores the contribution of neutrophils to the pathologic changes in the injured spinal cord.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1126/scitranslmed.abq4744
