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Non-invasive imaging of the human spinal cord is a vital tool for understanding the mechanisms underlying its functions in both healthy and pathological conditions. However, non-invasive imaging presents a significant methodological challenge because the spinal cord is difficult to access with conventional neurophysiological approaches, due to its proximity to other organs and muscles, as well as the physiological movements caused by respiration, heartbeats, and cerebrospinal fluid (CSF) flow. Here, we discuss the present state and future directions of spinal cord imaging, with a focus on the estimation of current flow through magnetic field measurements. We discuss existing cryogenic (superconducting) and non-cryogenic (optically-pumped magnetometer-based, OPM) systems, and highlight their strengths and limitations for studying human spinal cord function. While significant challenges remain, particularly in source imaging and interference rejection, magnetic field-based neuroimaging offers a novel avenue for advancing research in various areas. These include sensorimotor processing, cortico-spinal interplay, brain and spinal cord plasticity during learning and recovery from injury, and pain perception. Additionally, this technology holds promise for diagnosing and optimizing the treatment of spinal cord disorders. [ABSTRACT FROM AUTHOR]

Background: Bilateral diaphragmatic dysfunction can lead to dyspnea and recurrent respiratory failure. In rare cases, it may result from high cervical spinal cord ischemia (SCI) due to anterior spinal artery syndrome (ASAS). We present a case of a patient experiencing persistent isolated diaphragmatic paralysis after SCI at level C3/C4 following thoracic endovascular aortic repair (TEVAR) for Kommerell's diverticulum. This is, to our knowledge, the first documented instance of a patient fully recovering from tetraplegia due to SCI while still exhibiting ongoing bilateral diaphragmatic paralysis. Case presentation: The patient, a 67-year-old male, presented to the Vascular Surgery Department for surgical treatment of symptomatic Kommerell's diverticulum in an aberrant right subclavian artery. After successful surgery in two stages, the patient presented with respiratory insufficiency and flaccid tetraparesis consistent with anterior spinal artery syndrome with maintained sensibility of all extremities. A computerized tomography scan (CT) revealed a high-grade origin stenosis of the left vertebral artery, which was treated by angioplasty and balloon-expandable stenting. Consecutively, the tetraparesis immediately resolved, but weaning remained unsuccessful requiring tracheostomy. Abdominal ultrasound revealed a residual bilateral diaphragmatic paralysis. A repeated magnetic resonance imaging (MRI) 14 days after vertebral artery angioplasty confirmed SCI at level C3/C4. The patient was transferred to a pulmonary clinic with weaning center for further recovery. Conclusions: This novel case highlights the need to consider diaphragmatic paralysis due to SCI as a cause of respiratory failure in patients following aortic surgery. Diaphragmatic paralysis may remain as an isolated residual in these patients. [ABSTRACT FROM AUTHOR]

Neurodegeneration refers to progressive dysfunction or loss of selectively vulnerable neurones from brain and spinal cord regions. Despite important advances in fluid and imaging biomarkers, the definitive diagnosis of most neurodegenerative diseases still relies on neuropathological examination. Not only has careful clinicopathological correlation shaped current clinical diagnostic criteria and informed our understanding of the natural history of neurodegenerative diseases, but it has also identified conditions with important public health implications, including variant Creutzfeldt-Jakob disease, iatrogenic amyloid-β and chronic traumatic encephalopathy. Neuropathological examination may also point to previously unsuspected genetic diagnoses with potential implications for living relatives. Moreover, detailed neuropathological assessment is crucial for research studies that rely on curated postmortem tissue to investigate the molecular mechanisms responsible for neurodegeneration and for biomarker discovery and validation. This review aims to elucidate the hallmark pathological features of neurodegenerative diseases commonly seen in general neurology clinics, such as Alzheimer's disease and Parkinson's disease; rare but well- known diseases, including progressive supranuclear palsy, corticobasal degeneration and multiple system atrophy and more recently described entities such as chronic traumatic encephalopathy and age- related tau astrogliopathy. [ABSTRACT FROM AUTHOR]

Background/Aim: To compare implant sparing irradiation with conventional radiotherapy (RT) using helical (H) and TomoDirect (TD) techniques in breast cancer patients undergoing immediate breast reconstruction (IBR). Patients and Methods: The dosimetric parameters of 40 patients with retropectoral implants receiving 50.4 Gy delivered in 28 fractions were analyzed. Three plans were created: H plan using conventional planning target volume (PTV) that included the chest wall, skin, and implant; TD plan using conventional PTV; and Hs plan using implantsparing PTV. The H, TD, and Hs plans were compared for PTV doses, organ-at-risk (OAR) doses, and treatment times. Results: Dose distribution in the Hs plan was less homogeneous and uniform than that in the H and TD plans. The TD plan had lower lung, heart, contralateral breast, spinal cord, liver, and esophagus doses than the Hs plan. Compared to the Hs plan, the H plan had lower lung volume receiving 5Gy (V5) (39.1±3.9 vs. 41.2±3.9 Gy; p<0.001), higher V20 (12.3±1.3 vs. 11.5±2.6 Gy; p=0.02), and higher V30 (7.5±1.6 vs. 4.4±1.7 Gy; p<0.001). H plan outperformed Hs plan in heart dosimetric parameters except V20. The Hs plan had significantly lower mean implant doses (43.4±2.1 Gy) than the H plan (51.4±0.5 Gy; p<0.001) and the TD plan (51.9±0.6 Gy; p<0.001). Implementing an implant sparing technique for silicone dose reduction decreases lung doses. Conclusion: Conventional H and TD plans outperform the implant sparing helical plan dosimetrically. Because capsular contracture during RT is unpredictable, long-term clinical outcomes are required to determine whether silicon should be spared. [ABSTRACT FROM AUTHOR]

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Introduction/Aims: In amyotrophic lateral sclerosis (ALS), the role of spinal interneurons in ALS is underrecognized. We aimed to investigate pre‐ and post‐synaptic modulation of spinal motor neuron excitability by studying the H reflex, to understand spinal interneuron function in ALS. Methods: We evaluated the soleus H reflex, and three different modulation paradigms, to study segmental spinal inhibitory mechanisms. Homonymous recurrent inhibition (H'RI) was assessed using the paired H reflex technique. Presynaptic inhibition of Ia afferents (H'Pre) was evaluated using D1 inhibition after stimulation of the common peroneal nerve. We also studied inhibition of the H reflex after cutaneous stimulation of the sural nerve (H'Pos). Results: Fifteen ALS patients (median age 57.0 years), with minimal signs of lower motor neuron involvement and good functional status, and a control group of 10 healthy people (median age 57.0 years) were studied. ALS patients showed reduced inhibition, compared to controls, in all paradigms (H'RI 0.35 vs. 0.11, p =.036; H'Pre 1.0 vs. 5.0, p =.001; H'Pos 0.0 vs. 2.5, p =.031). The clinical UMN score was a significant predictor of the amount of recurrent and presynaptic inhibition. Discussion: Spinal inhibitory mechanisms are impaired in ALS. We argue that hyperreflexia could be associated with dysfunction of spinal inhibitory interneurons. In this case, an interneuronopathy could be deemed a major feature of ALS. [ABSTRACT FROM AUTHOR]

Objectives: Advances in Spinal cord stimulation (SCS) device technology in recent years have led to the development of SCS systems that are magnetic resonance imaging (MRI)‐conditional, most of which are dependent on normal lead impedances. The objective of this study was to retrospectively analyze the rate of elevated lead impedance in these devices to determine the rate of failure of MR‐conditional modes. Materials and Methods: This was a single‐center, retrospective, chart‐based review conducted during a five‐year period. Patients were included if they had been implanted with an impedance‐dependent MR‐conditional SCS and had a documented impedance check at least 6 months after implantation. A Kaplan–Meier survival analysis was performed to map the survival of MR‐conditionality over time. Results: There were 363 cases included between 2015 and 2020, which corresponded to a total of 602 SCS leads. Nevro was the most common manufacturer (67.8%), followed by Boston Scientific (22.3%) and Abbott (9.9%). The average overall follow‐up time was 2.25 years. Overall, 67 (18.5%) of patients had lead impedances over 10,000 Ω at follow‐up with a total of 186 electrode contacts (3.9%). Leads most commonly had either one (40%), two (22%) or three (12%) electrode contacts out of range. Risk of failure of lead impedances increased by 35.4% with each successive year to a peak of 43% of all leads by year 5. Mean overall survival time of normal lead impedances was 4.77 years (CI 4.40–5.13). There was no statistically significant difference in mean overall survival time between Abbott (M = 4.0 years, SD = 1.25), Boston Scientific (M = 4.64 years, SD = 1.75) and Nevro (M = 4.80 years, SD = 3.28), χ2 (2, N = 358) = 1.511, p = 0.47; however, Abbott leads had a greater total number of failed impedance contacts (50/568, 8.8%), in comparison to Nevro (124/3064, 4.0%), χ2 (1, N = 3630) = 23.76, p < 0.00001, at a similar follow‐up time. Conclusion: This retrospective study identified elevated impedances in 18.5% of MR‐conditional SCS devices at an average of 2.25 years follow‐up resulting in loss of MR‐conditionality and a mean overall lead survival time of 4.77 years for normal lead impedance. [ABSTRACT FROM AUTHOR]

Objective Determine the effectiveness of intradiscal corticosteroid injection (IDCI) for the treatment of discovertebral low back pain. Design Systematic review. Population Adults with chronic low back pain attributed to disc or vertebral end plate pain, as evidenced by positive provocation discography or Modic 1 or 2 changes on magnetic resonance imaging. Intervention Fluoroscopically guided or computed tomography–guided IDCI. Comparison Sham/placebo procedure including intradiscal saline, anesthetic, discography alone, or other active treatment. Outcomes Reduction in chronic low back pain reported on a visual analog scale or numeric rating scale and reduction in disability reported by a validated scale such as the Oswestry Disability Index. Methods Four reviewers independently assessed articles published before January 31, 2023, in Medline, Embase, CENTRAL, and CINAHL. The quality of evidence was evaluated with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The risk of bias in randomized trials was evaluated with the Cochrane Risk of Bias tool (version 2). Results Of the 7806 unique records screened, 6 randomized controlled trials featuring 603 total participants ultimately met the inclusion criteria. In multiple randomized controlled trials, IDCI was found to reduce pain and disability for 1–6 months in those with Modic 1 and 2 changes but not in those selected by provocation discography. Conclusion According to GRADE, there is low-quality evidence that IDCI reduces pain and disability for up to 6 months in individuals with chronic discovertebral low back pain as evidenced by Modic 1 and 2 changes but not in individuals selected by provocation discography. Study registration PROSPERO (CRD42021287421). [ABSTRACT FROM AUTHOR]

Postural and spinal deformities are major contributing factors to musculoskeletal (MSK) disorders. Posture screening and assessment can help to identify early morphological deformities, thereby preventing progression and reducing or correcting them with effective treatments. The study evaluates both intra- and inter-repeatability of using a mobile structured light sensor with a structured light pattern for building an accurate 3D human model and its use in postural screening. 16 young males (age: 25 ± 5.6 years, height: 172 ± 5.3 cm, mass: 69 ± 8.6 kg) participated without any musculoskeletal pain or pre-existing leg or spinal abnormalities. An iPad-based 3D mobile scanning tool, Structure SensorTM (2018 version), was used to capture the participants' back and whole-body shape. The collected data (3D model) were realigned and processed in the open-source software, Netfabb BasicTM (7.2 version). For each participant, five trained raters individually measured three trials of standing back and body posture on two separate occasions to calculate both intra- and inter-rater reliability. With the use of this software, nine postural variables and angular displacements were individually measured by the raters. The results indicated good to excellent intra-rater and good to moderate inter-rater reliability for measuring 78% (7 out of 9) of postural variables with an ICC ranging from 0.70 to 0.98. The remaining 22% of variables (2 out of 9; lateral pelvic tilt and right frontal knee angle) showed moderate to low inter- and intra-rater reliability, with ICCs ranging from 0.26 to 0.79. [ABSTRACT FROM AUTHOR]

To update the state of the art regarding the acquisition of spinal high-velocity low-amplitude psychomotor skills competency among chiropractors and chiropractic students. Available electronic articles from 5 databases, published between June 2015 and August 2020, were obtained. Eligible studies underwent methodological quality assessments using the Joanna Briggs Institute Critical Appraisal Checklists and Cochrane Collaboration's Risk of Bias Tools. Fourteen critically appraised studies were identified, including 10 cohort studies and 4 randomized controlled trials. There was no literature excluded due to high risk of bias. The type of augmented devices included a mannequin on a force platform, a computer-connected device, a human analogue mannequin, and a 3-dimensional electrogoniometer with an instrumented spatial linkage. The use of augmented feedback devices such as human analogue mannequins with force-sensing table technology and computer-connected devices is potentially beneficial in the chiropractic curricula and may facilitate student learning and improvement of spinal manipulation. More studies are required to determine whether psychomotor skill aids translate directly into raised competency levels in novice clinicians. [ABSTRACT FROM AUTHOR]

A spinal cord injury (SCI) can be a devastating condition in children, with profound implications for their overall health and quality of life. In this review, we aim to provide a concise overview of the key aspects associated with SCIs in the pediatric population. Firstly, we discuss the etiology and epidemiology of SCIs in children, highlighting the diverse range of causes. We explore the unique anatomical and physiological characteristics of the developing spinal cord that contribute to the specific challenges faced by pediatric patients. Next, we delve into the clinical presentation and diagnostic methods, emphasizing the importance of prompt and accurate diagnosis to facilitate appropriate interventions. Furthermore, we approach the multidisciplinary management of pediatric SCIs, encompassing acute medical care, surgical interventions, and ongoing supportive therapies. Finally, we explore emerging research as well as innovative therapies in the field, and we emphasize the need for continued advancements in understanding and treating SCIs in children to improve their functional independence and overall quality of life. [ABSTRACT FROM AUTHOR]

BackgroundSpinal cord dose limits are critically important for the safe practice of spine stereotactic body radiotherapy (SBRT). However, the effect of inherent spinal cord motion on cord dose in SBRT is unknown.ObjectiveTo assess the effects of cord motion on spinal cord dose in SBRT.MethodsDynamic balanced fast field echo (BFFE) magnetic resonance imaging (MRI) was obtained in 21 spine metastasis patients treated with SBRT. Planning computed tomography (CT), conventional static T2-weighted MRI, BFFE MRI, and dose planning data were coregistered. Spinal cord from the dynamic BFFE images (corddyn) was compared with the T2-weighted MRI (cordstat) to analyze motion of corddyn beyond the cordstat (Dice coefficient, Jaccard index), and beyond cordstat with added planning organ at risk volume (PRV) margins. Cord dose was compared between cordstat, and corddyn (Wilcoxon signed-rank test).ResultsDice coefficient (0.70-0.95, median 0.87) and Jaccard index (0.54-0.90, median 0.77) demonstrated motion of corddyn beyond cordstat. In 62% of the patients (13/21), the dose to corddyn exceeded that of cordstat by 0.6% to 13.8% (median 4.3%). The corddyn spatially excursed outside the 1-mm PRV margin of cordstat in 9 patients (43%); among these dose to corddyn exceeded dose to cordstat >+ 1-mm PRV margin in 78% of the patients (7/9). Corddyn did not excurse outside the 1.5-mm or 2-mm PRV cord cordstat margin.ConclusionSpinal cord motion may contribute to increases in radiation dose to the cord from SBRT for spine metastasis. A PRV margin of at least 1.5 to 2 mm surrounding the cord should be strongly considered to account for inherent spinal cord motion.

Background: This study investigated the efficacy of electrical nerve stimulation for neuromuscular and functional performance recovery after acute traumatic spinal cord injury (TSCI). Methods: Twenty-nine participants with TSCI (20 males and 9 females) were randomly assigned to study group (SG) and control group (CG). Treatment started within 24 h of injury at 3 days/week for 24 weeks. Both groups were treated with a functional re-education approach while SG had electrical nerve stimulation in addition. The American Spinal Cord Injury Association (ASIA) scale was used to assess the severity of TSCI, the Spinal Cord Independence Measure evaluated functional performance, Neuromuscular Recovery Scale measured neuromuscular recovery, Walking Index assessed walking function, and a tape rule was used to measure participants' girth. Measurements were taken at baseline and every 6 weeks thereafter. Data were analyzed using the Friedman Analysis of Variance, the Wilcoxon–rank test, and Independent t-test. Results: Participants were aged 15–58 years (mean = 36.75 ± 11.75 and median = 37 years), with 19 (65.5%) within 19–40 years' range. Eighteen (62.1%) had cervical, three (10.2%) thoracic, and eight (27.5%) had lumbar TSCI. Nine (31.0%) each presented with ASIA-A and ASIA-C, seven (24.1%) ASIA-B, and four (13.9%) ASIA-D. Consistent significant (P < 0.05) improvement in neuromuscular and functional performance recovery within SG as compared with CG was recorded, with improvements across the five points of measurement. Walking function improved clinically in SG and no muscle atrophy was recorded throughout 24 weeks. The level of statistical significance was set at P < 0.05. Conclusion: Electrical nerve stimulation combined with early functional re-training effectively improves neuromuscular and functional performance recovery in acute TSCI. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms arising in the gastrointestinal tract, especially in the stomach (60–65%). The development of most cases of GISTs is associated with activating mutations in the receptor tyrosine kinase genes KIT and PDGFRA. The discovery of mutations leads to the approval of tyrosine kinase inhibitors (TKIs) for GISTs. Considering the recent approval of the last two TKIs and given their increased use in clinical practice, a spontaneous reporting system (SRS) database, the main tool in pharmacovigilance, takes a remarkable role in promptly characterizing the benefit/risk profile of these new drugs and consequently improve the quality of life of patients affected by GISTs. Tyrosine kinase inhibitors (TKIs) are widely used in gastrointestinal stromal tumors (GISTs). The aim of this study is to evaluate the reporting frequency of neuropsychiatric adverse drug reactions (ADRs) for TKIs through the analysis of European individual case safety reports (ICSRs). All ICSRs collected in EudraVigilance up to 31 December 2021 with one TKI having GISTs as an indication (imatinib (IM), sunitinib (SU), avapritinib (AVA), regorafenib (REG), and ripretinib (RIP)) were included. A disproportionality analysis was performed to assess the frequency of reporting for each TKI compared to all other TKIs. The number of analyzed ICSRs was 8512, of which 57.9% were related to IM. Neuropsychiatric ADRs were reported at least once in 1511 ICSRs (17.8%). A higher reporting probability of neuropsychiatric ADRs was shown for AVA. Most neuropsychiatric ADRs were known, except for a higher frequency of lumbar spinal cord and nerve root disorders (reporting odds ratio, ROR 4.46; confidence interval, CI 95% 1.58–12.54), olfactory nerve disorders (8.02; 2.44–26.33), and hallucinations (22.96; 8.45–62.36) for AVA. The analyses of European ICSRs largely confirmed the safety profiles of TKIs in GISTs, but some ADRs are worthy of discussion. Further studies are needed to increase the knowledge of the neuropsychiatric disorders of newly approved TKIs. [ABSTRACT FROM AUTHOR]

SYNOPSIS: Central sensitization is an umbrella-term for facilitated synaptic plasticity. This editorial explains wind-up, classical central sensitization, and long-term potentiation. Wind-up and LTP are generally considered homosynaptic, while classical central sensitization is classified as heterosynaptic. Wind-up is very short lived and unlikely to play a significant role in chronic musculoskeletal pain, however, both LTP and classical central sensitization could potentially be involved in chronic pain. [ABSTRACT FROM AUTHOR]

BACKGROUND: Proton MR spectroscopy (H1-MRS) is currently considered a useful technique for evaluating axonal damage and demyelination in MS; however, only few spectroscopic cervical MS studies have been published because of the technical difficulties. To assess the diagnostic role of MRS in evaluation of MS patients and to evaluate metabolic profile in spinal cord MS plaques as well as NAWM. Methods: a comparative study between MS cases and control group in which twenty patients with multiple sclerosis were encountered in the study and subjected to clinical assessment including full history taking, clinical examination and imaging assessment by conventional MRI and functional MRI. Additional 20 healthy control individuals of the same age and gender group were included in the study. We determined the metabolic profile of each case and compared it with the control group. Results: comparison of the main metabolite ratios between different studied groups (MS cord plaque group and control group), Cho/Cr, NAA/Cr, mI/Cr, and NAA/Cho of control group were 0.52 ± 0.1, 1.1 ± 0.15, 1.4 ± 0.13, and 3.9 ± 0.9, acute MS group were 0.62 ± 0.08, 1.3 ± 0.02, 2.3 ± 0.2, and 2.0 ± 0.04, relapsing MS group were 0.55 ± 0.06, 1.4 ± 0.1, 1.6 ± 0.3, and 1.4 ± 0.08 and progressive MS group were 0.59 ± 0.02, 0.9 ± 0.03, 2.08 ± 0.04, and 1.2 ± 0.06 with P value < 0.001. Conclusions: to evaluate the diagnostic role of MRS in the evaluation of MS patients and to evaluate the metabolic profile in spinal cord MS plaques as well as normal-appearing white matter. [ABSTRACT FROM AUTHOR]

Background: Gabapentin is a recommended first‐line agent for treating neuropathic pain; however, its efficacy rate is reportedly low, and the risk of adverse events is high. A plausible explanation for this lies with its wide range of actions, the entirety of which have yet to be fully elucidated. Methods: A review of the literature was conducted on gabapentin's known and proposed analgesic mechanisms of action, as well as potentially opposing or detrimental actions. Results: Gabapentin's classical analgesic mechanisms involve direct attenuation of excitatory neurotransmission in the spinal cord via inhibition of neuronal ion channels, while indirect mechanisms include descending inhibition and block of injury‐evoked synaptogenesis. Glial effects have also been reported; however, whether they are neuroprotective or detrimental is unknown. Furthermore, data from animal models do not reflect clinical outcomes. Conclusions: Gabapentin's clinical use should be reconsidered according to the net effects of its numerous assumed actions, including the tripartite synapse and oligodendrocyte effects. Whether it is doing more harm than good, especially in the scenarios of incomplete or loss of response, warrants consideration when prescribing gabapentin. [ABSTRACT FROM AUTHOR]

Patients with traumatic spinal cord injury have a vast array of secondary pathophysiologic effects, one of which is autonomic dysreflexia (AD). It can be triggered by noxious stimuli and cause severe and fatal consequences that require rapid intervention. This article examines AD and its implications for nursing care. Patients with traumatic spinal cord injury have a vast array of secondary complications, one of which is autonomic dysreflexia (AD). This article examines AD and its implications for nursing care. [ABSTRACT FROM AUTHOR]

Electroacupuncture (EA) combines traditional Chinese medicine acupuncture theory with modern scientific technology. It is a promising therapy for the treatment of cerebrovascular diseases such as cerebral infarction. A large number of clinical studies have shown that EA promotes recovery of neurological function after cerebral infarction, however, the underlying mechanisms behind its effects remain unclear. We tested whether EA stimulation of the Zusanli (ST36) and Neiguan (PC6) acupoints activates neuroplasticity in rats with ischemic stroke and whether this involves the regulation of axonal regeneration through the mTOR pathway. 24 h after permanent middle cerebral artery occlusion (p-MCAO) in rats, EA treatment was started for 20 min, daily, for 14 days. We found that EA significantly reduced Modified Neurological Severity Scores (mNSS), cerebral infarct volume, and apoptosis of neuronal cells. EA also significantly increased the expression of the neuroplasticity-associated proteins GAP-43 and SYN and upregulated the phosphorylation levels of AKT, mTOR, S6, and PTEN to promote CST axon sprouting in the spinal cord at C1–C4 levels. The positive effects of EA were blocked by the administration of the mTOR inhibitor Rapamycin. In short, we found that EA of the Zusanli (ST36) and Neiguan (PC6) acupoints in p-MCAO rats induced neuroprotective and neuroplastic effects by regulating the mTOR signaling pathway. It promoted neuroplasticity activated by axon regeneration in the contralateral cortex and corticospinal tract. Activation of such endogenous remodeling is conducive to neurological recovery and may help explain the positive clinical effects seen in patients with infarcts. [ABSTRACT FROM AUTHOR]

Abstract: Despite being involved in a number of functions, such as nociception and locomotion, spinal lamina X remains one of the least studied central nervous system regions. Here, we show that Aδ- and C-afferent inputs to lamina X neurons are presynaptically inhibited by homo- and heterosegmental afferents as well as by descending fibers from the corticospinal tract, dorsolateral funiculus, and anterior funiculus. Activation of descending tracts suppresses primary afferent-evoked action potentials and also elicits excitatory (mono- and polysynaptic) and inhibitory postsynaptic responses in lamina X neurons. Thus, primary afferent input to lamina X is subject to both spinal and supraspinal control being regulated by at least 5 distinct pathways. [ABSTRACT FROM AUTHOR]

Transcutaneous spinal cord stimulation (tSCS) is becoming a promising neuromodulation technique to promote motor recovery in various neurological conditions, including stroke. As this intervention moves forward into clinical practice, it is important to understand how the elicited neurophysiological measures are related to the functional and neuromuscular deficits of the population of interest in order to personalize tSCS interventions and assess its effectiveness. Specifically, neurophysiological measurements of spinal cord excitability can be achieved by recording with EMG spinal motor evoked responses (sMERs) in muscles after applying single pulses of tSCS to the spinal cord. The objective of this study was to investigate potential correlations between baseline spinal cord excitability, as measured by resting motor threshold (RMT) and peak-to-peak (P2P) amplitude of the sMERs, and various factors including demographic characteristics, severity of spasticity, muscle strength, and gait speed in individuals post-stroke. Additionally, the study sought to explore disparities in excitability between the paretic and non-paretic sides. Fifteen participants with chronic stroke underwent sMER assessments. We observed a strong positive correlation between RMT and body weight, indicating weight as a potential confounding variable when comparing RMTs from sMERs between individuals. Furthermore, paretic muscles exhibited lower RMTs and higher P2P amplitudes compared to non-paretic muscles. The results demonstrate that sMERs hold promise in uncovering disparities in spinal excitability in stroke participants. Furthermore, careful interpretation and analysis of sMERs is advised, particularly as higher RMTs were associated with higher body weight and could impact the clinical feasibility of tSCS for some participants. These results should be considered in future tSCS protocols that aim to develop more personalized interventions across different neurological populations and optimize sMERs' utility as an outcome measure., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Veit et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Here we test the stochastic dynamic operator (SDO) as a new framework for describing physiological signal dynamics relative to spiking or stimulus events. The SDO is a natural extension of existing spike-triggered average (STA) or stimulus-triggered average techniques currently used in neural analysis. It extends the classic STA to cover state-dependent and probabilistic responses where STA may fail. In simulated data, SDO methods were more sensitive and specific than the STA for identifying state-dependent relationships. We have tested SDO analysis for interactions between electrophysiological recordings of spinal interneurons, single motor units, and aggregate muscle electromyograms (EMG) of major muscles in the spinal frog hindlimb. When predicting target signal behavior relative to spiking events, the SDO framework outperformed or matched classical spike-triggered averaging methods. SDO analysis permits more complicated spike-signal relationships to be captured, analyzed, and interpreted visually and intuitively. SDO methods can be applied at different scales of interest where spike-triggered averaging methods are currently employed, and beyond, from single neurons to gross motor behaviors. SDOs may be readily generated and analyzed using the provided SDO Analysis Toolkit We anticipate this method will be broadly useful for describing dynamical signal behavior and uncovering state-dependent relationships of stochastic signals relative to discrete event times., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Smith et al.)

Voltage imaging holds great potential for biomedical research by enabling noninvasive recording of the electrical activity of excitable cells such as neurons or cardiomyocytes. Camera-based detection can record from hundreds of cells in parallel, but imaging entire volumes is limited by the need to focus through the sample at high speeds. Remote focusing techniques can remedy this drawback, but have so far been either too slow or light-inefficient. Here, we introduce flipped image remote focusing, a remote focusing method that doubles the light efficiency compared to conventional beamsplitter-based techniques and enables high-speed volumetric voltage imaging at 500 volumes/s. We show the potential of our approach by combining it with light sheet imaging in the zebrafish spinal cord to record from >100 spontaneously active neurons in parallel., (© 2024. The Author(s).)

Mechanisms controlling the movement of the cerebrospinal fluid (CSF) toward peripheral nerves are poorly characterized. We found that, in addition to the foramina Magendie and Luschka for CSF flow toward the subarachnoid space and glymphatic system, CSF outflow could also occur along periaxonal spaces (termed "PAS pathway") from the spinal cord to peripheral organs, such as the liver and pancreas. When interrogating the latter route, we found that serotonin, acting through 5-HT 2B receptors expressed in ependymocytes that line the central canal, triggered Ca 2+ signals to induce polymerization of F-actin, a cytoskeletal protein, to reduce the volume of ependymal cells. This paralleled an increased rate of PAS-mediated CSF redistribution toward peripheral organs. In the liver, CSF was received by hepatic stellate cells. CSF efflux toward peripheral organs through the PAS pathway represents a mechanism dynamically connecting the nervous system with the periphery. Our findings are compatible with the traditional theory of CSF efflux into the glymphatic system to clear metabolic waste from the cerebral parenchyma. Thus, we extend the knowledge of CSF flow and expand the understanding of connectivity between the CNS and peripheral organs., Competing Interests: Competing interests statement:The authors declare no competing interest.

Spinal projection neurons (PNs) are defined by long axons that travel from their origin in the spinal cord to the brain where they relay sensory information from the body. The existence and function of a substantial axon collateral network, also arising from PNs and remaining within the spinal cord, is less well appreciated. Here we use a retrograde viral transduction strategy to characterise a novel subpopulation of deep dorsal horn spinoparabrachial neurons. Brainbow assisted analysis confirmed that virally labelled PN cell bodies formed a discrete cell column in the lateral part of Lamina V (LV lat ) and the adjoining white matter. These PNs exhibited large dendritic territories biased to regions lateral and ventral to the cell body column and extending considerable rostrocaudal distances. Optogenetic activation of LV Lat PNs confirmed this population mediates widespread signalling within spinal cord circuits, including activation in the superficial dorsal horn. This signalling was also demonstrated with patch clamp recordings during LV Lat PN photostimulation, with a range of direct and indirect connections identified and evidence of a postsynaptic population of inhibitory interneurons. Together, these findings confirm a substantial role for PNs in local spinal sensory processing, as well as relay of sensory signals to the brain., (© 2024. The Author(s).)

Reciprocal inhibition (RI) between leg muscles is crucial for smooth movement. Pedaling is a rhythmic movement that can increase RI in healthy individuals. Transcutaneous spinal cord stimulation (tSCS) stimulates spinal neural circuits by targeting the afferent fibers. Pedaling with simultaneous tSCS may modulate the plasticity of the spinal neural circuit and alter neural activity based on movement and muscle engagement. This study investigated the RI changes after pedaling and tSCS and determined the phase of pedaling in which tSCS should be applied for optimal RI modulation in healthy individuals. Eleven subjects underwent three interventions: pedaling combined with tSCS during the early phase of lower extension (phase 1), pedaling combined with tSCS during the late phase of lower flexion (phase 4) of the pedaling cycle, and pedaling combined with sham tSCS. The RI from the tibialis anterior to the soleus muscle was assessed before, immediately after, 15 min, and 30 min after the intervention. RI increased immediately after phase 4 and pedaling combined with sham tSCS, whereas no changes were observed after phase 1. These results demonstrate that tSCS modulates RI changes induced by pedaling in a stimulus phase-dependent manner in healthy individuals. However, the mechanism involved in this intervention needs to be explored to achieve higher efficacy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Respiratory muscle paralysis due to trauma or neurodegenerative diseases can have devastating consequences. Only a few studies have investigated the reconstruction of motor function in denervated diaphragms caused by such conditions. Here, we studied the efficacy of transplanting E14 embryonic spinal motor neurons (SMNs) into peripheral nerve grafts for functionally reconstructing a denervated diaphragm in a rat model. The diaphragms of 8-week-old male Fischer 344 rats were first denervated by transecting the phrenic nerves. Subsequently, peripheral nerve grafts taken from the lower limb were used for neurotization of the denervated diaphragms. One week later, fetal E14 SMNs were transplanted into the peripheral nerve grafts. After 3 months, we observed functional contraction of the diaphragm following neuromuscular electrical stimulation (NMES) of the peripheral nerve graft. Additionally, we confirmed that SMN transplantation into the peripheral nerve graft had an inhibitory effect on diaphragm muscle atrophy. The SMNs transplanted into the peripheral nerve grafts formed a structure similar to the spinal cord, and the neuromuscular junction of the denervated diaphragm was reinnervated. These findings suggest the establishment of an ectopic motor neuron pool in the peripheral nerve graft. Free peripheral intra-nerve SMN transplantation in combination with NMES, which can be applied for diaphragmatic pacing, offers novel insights into the development of neuroregenerative therapies for treating life-threatening and intractable respiratory muscle paralysis caused by severe nerve damage and degenerative diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Unlike mammals, species such as fish and amphibians can regenerate damaged spinal cords, offering insights into potential therapeutic targets. This study investigates the structural features of the molly fish spinal cord through light and electron microscopy. The most notable characteristic was the presence of Mauthner cells (M-cells), which exhibited large cell bodies and processes, as well as synaptic connections with astrocytes. These astrocytic connections contained synaptic vesicles, suggesting electrical transmission at the M-cell endings. Astrocytes, which were labeled with glial fibrillary acidic protein (GFAP), contained cytoplasmic glycogen granules, potentially serving as an emergency fuel source. Two types of oligodendrocytes were identified: a small, dark cell and a larger, lighter cell, both of which reacted strongly with oligodendrocyte transcription factor 2 (Olig2). The dark oligodendrocyte resembled human oligodendrocyte precursors, while the light oligodendrocyte was similar to mature human oligodendrocytes. Additionally, proliferative neurons in the substantia grisea centralis expressed myostatin, Nrf2, and Sox9. Collectively, these findings suggest that the molly fish spinal cord has advanced structural features conducive to spinal cord regeneration and could serve as an excellent model for studying central nervous system regeneration. Further studies on the functional aspects of the molly fish spinal cord are recommended. RESEARCH HIGHLIGHTS: Mauthner cells (M-cell), with their typical large cell body and processes, were the most characteristic feature in Molly fish spinal cord, where it presented synaptic connections with astrocytes and their ends contained synaptic vesicles indicating an electrical transmission in the M-cells endings. Two types of oligodendrocytes could be recognized; both reacted intensely with Oligodendrocyte transcription factor 2 (Olig2). The proliferative neurons of the substantia grisea centralis expressed myostatin, Nrf2, and Sox9. The findings of this study suggest that molly fish possess highly developed structural features conducive to spinal cord regeneration. Consequently, they could be deemed an exemplary model for investigating central nervous system regeneration., (© 2024 Wiley Periodicals LLC.)

The spinal cord is of fundamental importance for integrative processing in brain-body communication, yet routine noninvasive recordings in humans are hindered by vast methodological challenges. Here, we overcome these challenges by developing an easy-to-use electrophysiological approach based on high-density multichannel spinal recordings combined with multivariate spatial-filtering analyses. These advances enable a spatiotemporal characterization of spinal cord responses and demonstrate a sensitivity that permits assessing even single-trial responses. To furthermore enable the study of integrative processing along the neural processing hierarchy in somatosensation, we expand this approach by simultaneous peripheral, spinal, and cortical recordings and provide direct evidence that bottom-up integrative processing occurs already within the spinal cord and thus after the first synaptic relay in the central nervous system. Finally, we demonstrate the versatility of this approach by providing noninvasive recordings of nociceptive spinal cord responses during heat-pain stimulation. Beyond establishing a new window on human spinal cord function at millisecond timescale, this work provides the foundation to study brain-body communication in its entirety in health and disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nierula et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Sensory substitution offers a promising approach to restore lost sensory functions. Here we show that spinal cord stimulation (SCS), typically used for chronic pain management, can potentially serve as a novel auditory sensory substitution device. We recruited 13 patients undergoing SCS implantation and translated everyday sound samples into personalized SCS patterns during their trial phase. In a sound identification task-where chance-level performance was 33.3%-participants ( n = 8 ) achieved a mean accuracy of 72.8% using only SCS input. We observed a weak positive correlation between stimulation bitrate and identification accuracy. A follow-up discrimination task ( n = 5 ) confirmed that reduced bitrates significantly impaired participants' ability to distinguish between consecutive SCS patterns, indicating effective processing of additional information at higher bitrates. These findings demonstrate the feasibility of using existing SCS technology to create a novel neural interface for a sound prosthesis. Our results pave the way for future research to enhance stimulation fidelity, assess long-term training effects, and explore integration with other auditory aids for comprehensive hearing rehabilitation., (© 2024. The Author(s).)

Long-term and non-narcotic hemodynamic imaging is indispensable for observing factual physiological information of the spinal cord. Unfortunately, achieving label-free, high-resolution, and widefield spinal cord imaging for mice under freely moving conditions is challenging. In this study, we developed a miniaturized photoacoustic microscope along with a corresponding photoacoustic spinal window to realize high-resolution, multi-segmental hemodynamic imaging of the spinal cord for freely moving mice. The microscope has an outer size of 32 mm × 23 mm × 10 mm, a weight of 5.8 g, and a 4.4 µm lateral resolution within an effective field of view (FOV) of 2.6 mm × 1.8 mm. To eliminate the off-focus phenomena during spinal imaging, the microscope is equipped with a miniature motor to adapt the focal plane. Besides, the microscope is slidable along a customized rail on the window to expand the FOV. We evaluated the stability of the microscope and analyzed vascular images of the spinal cord under various physiological states. The results suggest that the microscope is capable of performing stable, multi-segmental spinal cord imaging in freely moving mice, offering new insights into spinal cord hemodynamics and neurovascular coupling research.

Locomotion in mammals is directly controlled by the spinal neuronal network, operating under the control of supraspinal signals and somatosensory feedback that interact with each other. However, the functional architecture of the spinal locomotor network, its operation regimes, and the role of supraspinal and sensory feedback in different locomotor behaviors, including at different speeds, remain unclear. We developed a computational model of spinal locomotor circuits receiving supraspinal drives and limb sensory feedback that could reproduce multiple experimental data obtained in intact and spinal-transected cats during tied-belt and split-belt treadmill locomotion. We provide evidence that the spinal locomotor network operates in different regimes depending on locomotor speed. In an intact system, at slow speeds (<0.4 m/s), the spinal network operates in a non-oscillating state-machine regime and requires sensory feedback or external inputs for phase transitions. Removing sensory feedback related to limb extension prevents locomotor oscillations at slow speeds. With increasing speed and supraspinal drives, the spinal network switches to a flexor-driven oscillatory regime and then to a classical half-center regime. Following spinal transection, the model predicts that the spinal network can only operate in the state-machine regime. Our results suggest that the spinal network operates in different regimes for slow exploratory and fast escape locomotor behaviors, making use of different control mechanisms., Competing Interests: IR, NS, SM, BP, AF No competing interests declared, (© 2024, Rybak et al.)

Walking is a complex motor programme involving coordinated and distributed activity across the brain and the spinal cord. Halting appropriately at the correct time is a critical component of walking control. Despite progress in identifying neurons driving halting 1-6 , the underlying neural circuit mechanisms responsible for overruling the competing walking state remain unclear. Here, using connectome-informed models 7-9 and functional studies, we explain two fundamental mechanisms by which Drosophila implement context-appropriate halting. The first mechanism ('walk-OFF') relies on GABAergic neurons that inhibit specific descending walking commands in the brain, whereas the second mechanism ('brake') relies on excitatory cholinergic neurons in the nerve cord that lead to an active arrest of stepping movements. We show that two neurons that deploy the walk-OFF mechanism inhibit distinct populations of walking-promotion neurons, leading to differential halting of forward walking or turning. The brake neurons, by constrast, override all walking commands by simultaneously inhibiting descending walking-promotion neurons and increasing the resistance at the leg joints. We characterized two behavioural contexts in which the distinct halting mechanisms were used by the animal in a mutually exclusive manner: the walk-OFF mechanism was engaged for halting during feeding and the brake mechanism was engaged for halting and stability during grooming., (© 2024. The Author(s).)

Cerebral white matter lesions prevent cortico-spinal descending inputs from effectively activating spinal motoneurons, leading to loss of motor control. However, in most cases, the damage to cortico-spinal axons is incomplete offering a potential target for therapies aimed at improving volitional muscle activation. Here we hypothesize that, by engaging direct excitatory connections to cortico-spinal motoneurons, stimulation of the motor thalamus could facilitate activation of surviving cortico-spinal fibers thereby immediately potentiating motor output. To test this hypothesis, we identify optimal thalamic targets and stimulation parameters that enhance upper-limb motor-evoked potentials and grip forces in anesthetized monkeys. This potentiation persists after white matter lesions. We replicate these results in humans during intra-operative testing. We then design a stimulation protocol that immediately improves strength and force control in a patient with a chronic white matter lesion. Our results show that electrical stimulation targeting surviving neural pathways can improve motor control after white matter lesions., (© 2024. The Author(s).)

Walking in natural environments requires visually guided modifications, which can be more challenging when involving sideways steps rather than longer steps. This exploratory study investigated whether these two types of modifications involve different changes in the central drive to spinal motor neurons of leg muscles. Fifteen adults [age: 36 ± 6 (SD) years] walked on a treadmill (4 km/h) while observing a screen displaying the real-time position of their toes. At the beginning of the swing phase, a visual target appeared in front (forward) or medial-lateral (sideways) of the ground contact in random step cycles (approximately every third step). We measured three-dimensional kinematics and electromyographic activity from leg muscles bilaterally. Intermuscular coherence was calculated in the alpha (5-15 Hz), beta (15-30 Hz), and gamma bands (30-45 Hz) approximately 230 ms before and after ground contact in control and target steps. Results showed that adjustments toward sideways targets were associated with significantly higher error, lower foot lift, and higher cocontraction between antagonist ankle muscles. Movements toward sideways targets were associated with larger beta-band soleus (SOL): medial gastrocnemius (MG) coherence and a more narrow and larger peak of synchronization in the cumulant density before ground contact. In contrast, movements toward forward targets showed no significant differences in coherence or synchronization compared with control steps. Larger SOL:MG beta-band coherence and short-term synchronization were observed during sideways, but not forward, gait modifications. This suggests that visually guided gait modifications may involve differences in the central drive to spinal ankle motor neurons dependent on the level of task difficulty. NEW & NOTEWORTHY This exploratory study suggests a specific and temporally restricted increase of central (likely corticospinal) drive to ankle muscles in relation to visually guided gait modifications. The findings indicate that a high level of visual attention to control the position of the ankle joint precisely before ground contact may involve increased central drive to ankle muscles. These findings are important for understanding the neural mechanisms underlying visually guided gait and may help develop rehabilitation interventions.

Abstract: The thermal grill illusion (TGI), a phenomenon in which the juxtaposition of innocuous warm and cold temperatures on the skin elicits a burning sensation, offers a unique perspective to how pain occurs in response to harmless stimuli. We investigated the role of the spinal cord in the generation of the TGI across 2 experiments (total n = 80). We applied heat and cold stimuli to dermatomes, areas of skin innervated by a single spinal nerve, that mapped onto adjacent or nonadjacent spinal segments. Enhanced warm and burning ratings during the TGI were observed when cold and warm stimuli were confined within the same dermatome. Furthermore, we found the spatial organisation of warm and cold stimuli within and across dermatomes affected TGI perception. Perceived warmth and burning intensity increased when the cold stimulus projected to the segment more caudal to the warm stimulus, whereas perceived cold during the TGI decreased compared with the opposite spatial arrangement. This suggests that the perception of TGI is enhanced when cold afferents are projected to spinal segments positioned caudally in relation to those receiving warm afferents. Our results indicate distinct interaction of sensory pathways based on the segmental arrangement of afferent fibres and are consistent with current interpretations of the spread and integration of thermosensory information along the spinal cord., (Copyright © 2024 International Association for the Study of Pain.)

Locomotion and scratching are basic motor functions which are critically important for animal survival. Although the spinal circuits governing forward locomotion have been extensively investigated, the organization of spinal circuits and neural mechanisms regulating backward locomotion and scratching remain unclear. Here, we extend a model by Danner et al. to propose a spinal circuit model with asymmetrical cervical-lumbar layout to investigate these issues. In the model, the left-right alternation within the cervical and lumbar circuits is mediated by V 0 D and V 0 V commissural interneurons (CINs), respectively. With different control strategies, the model closely reproduces multiple experimental data of quadrupeds in different motor behaviors. Specifically, under the supraspinal drive, walk and trot are expressed in control condition, half-bound is expressed after deletion of V 0 V CINs, and bound is expressed after deletion of V0 (V 0 D and V 0 V ) CINs; in addition, unilateral hindlimb scratching occurs in control condition and synchronous bilateral hindlimb scratching appears after deletion of V 0 V CINs. Under the combined drive of afferent feedback and perineal stimulation, different coordination patterns between hindlimbs during BBS (backward-biped-spinal) locomotion are generated. The results suggest that (1) the cervical and lumbar circuits in the spinal network are asymmetrically recruited during particular rhythmic limb movements. (2) Multiple motor behaviors share a single spinal network under the reconfiguration of the spinal network by supraspinal inputs or somatosensory feedback. Our model provides new insights into the organization of motor circuits and neural control of rhythmic limb movements., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cerebellar transcranial direct current stimulation (ctDCS) modulates cerebellar cortical excitability in a polarity-dependent manner and affects inhibitory pathways from the cerebellum. The cerebellum modulates spinal reflex excitability via the vestibulospinal tract and other pathways projecting to the spinal motor neurons; however, the effects of ctDCS on the excitability of spinal motor neurons and vestibulospinal tract remain unclear. The experiment involved 13 healthy individuals. ctDCS (sham-ctDCS, anodal-ctDCS, and cathodal-ctDCS) was applied to the cerebellar vermis at 2 mA with an interval of at least 3 days between each condition. We measured the maximal M-wave (Mmax) and maximal H-reflex (Hmax) in the right soleus muscle to assess the excitability of spinal motor neurons. We applied galvanic vestibular stimulation (GVS) for 200 ms at 100 ms before tibial nerve stimulation to measure Hmax conditioned by GVS (GVS-Hmax) and calculated the change rate of Hmax by GVS as the excitability of vestibulospinal tract. We measured the Mmax, Hmax, and GVS-Hmax before, during, and after ctDCS in the sitting posture. No main effects of tDCS condition, main effects of time, or interaction effects were observed in Hmax/Mmax or the change rate of Hmax by GVS. It has been suggested that ctDCS does not affect the excitability of spinal motor neurons and vestibulospinal tract, as measured by neurophysiological methods, such as the H-reflex, in healthy individuals in a sitting posture. Effect of ctDCS on other descending pathways to spinal motor neurons, the neurological mechanism of tDCS and the cerebellar activity during the experiment may have contributed to these results. Therefore, we need to investigate the involvement of the cerebellum in Hmax/Mmax and the change rate of Hmax by GVS under different neuromodulation techniques and postural conditions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study evaluated the effects of cessation of both conventional low-frequency (50 Hz) and high-frequency (10 kHz) spinal cord stimulation (SCS) on the cardiospinal neural network activity in pigs with myocardial infarction (MI). The objective is to provide an insight into the memory effect of SCS., Materials and Methods: In nine Yorkshire pigs, chronic MI was created by delivering microspheres to the left circumflex coronary artery. Five weeks after MI, anesthetized pigs underwent sternotomy to expose the heart for performing acute ischemia intervention, and laminectomy to expose the T1-T4 spinal regions for extracellular in vivo neural recording and SCS. Cardiac ischemic-sensitive neurons were identified by selective responsiveness to left anterior descending (LAD) coronary artery occlusion. SCS episodes were delivered in a random order between low- (50 Hz) and high- (10 kHz) frequency, for 1 minute, at 90% of the motor threshold current. Neural firing and synchrony of ischemic-sensitive spinal neurons were evaluated before vs after SCS., Results: Using a 64-channel microelectrode array, 2711 spinal neurons were recorded extracellularly. LAD ischemia excited 228 neurons that were labeled as ischemic-responsive neurons. The cessation of 50-Hz SCS caused a higher activation than did inhibition of ischemic-responsive neurons (41 activated vs 19 inhibited), whereas the cessation of 10-kHz SCS caused an opposite response with higher inhibition (11 activated vs 28 inhibited, p < 0.01 vs 50 Hz). Termination of low-frequency SCS caused an increase in ischemic-responsive neuronal firing rate compared with high-frequency SCS (50 Hz: 0.39 Hz ± 0.16 Hz, 10 kHz: -0.11 Hz ± 0.057 Hz, p < 0.01). In addition, SCS delivered at 50 Hz increased the number of synchronized pairs of neurons by 205 pairs, whereas high-frequency SCS decreased the number of synchronized pairs by 345 pairs (p < 0.01)., Conclusions: High-frequency (10 kHz) stimulation provides persistent suppression of the ischemia-sensitive neurons after termination of SCS. In contrast, the spinal neural network reverted to excitatory state after termination of low-frequency (50 Hz) stimulation., Competing Interests: Conflict of Interest The authors reported no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Infrared neural stimulation (INS) emerges as a promising tool for stimulating the nervous system by its high spatial precision and absence of the use of exogenous agents into the tissue, which led to the first successful proof of concept in human brain. While neural networks have been the focal point of INS research, this technique is also non cell type specific as it triggers activity in non electrically excitable cells. Despite increasing interest, there remains to demonstrate well defined simultaneous astrocytic and neuronal signals in response to INS. Using calcium imaging, we show that INS has the capacity to initiate calcium signaling in both astrocytes and neurons simultaneously from the rostral lumbar spinal cord, each exhibiting distinct temporal and amplitude characteristics. Importantly, the mechanism underlying infrared-induced neuronal and astrocytic calcium signaling differ, with neuronal activity relying on sodium channels, whereas induced astrocytic signaling is predominantly influenced by extracellular calcium and TRPV4 channels. Furthermore, our findings demonstrate the frequency shift of neuronal calcium oscillations through infrared stimulation. By deepening our understanding in INS fundamentals, this technique holds great promise for advancing neuroscience, deepening our understanding of pathologies, and potentially paving the way for future clinical applications., (© 2024. The Author(s).)

Connectomics approaches are fundamentally changing the way scientists investigate the brain. Recently published connectomes have enabled dissection of the intricate motor circuits in the fly's version of the spinal cord on a synaptic level. This has allowed reconstruction of complete sensorimotor pathways in Drosophila., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Different speeds of locomotion require heterogeneous spinal populations, but a common mode of rhythm generation is presumed to exist. Here, we explore the cellular versus synaptic origins of spinal rhythmicity at different speeds by performing electrophysiological recordings from premotor excitatory interneurons in larval zebrafish. Chx10-labeled V2a neurons are divided into at least two morphological subtypes proposed to play distinct roles in timing and intensity control. Consistent with distinct rhythm generating and output patterning functions within the spinal V2a population, we find that descending subtypes are recruited exclusively at slow or fast speeds and exhibit intrinsic cellular properties suitable for rhythmogenesis at those speeds, while bifurcating subtypes are recruited more reliably at all speeds and lack appropriate rhythmogenic cellular properties. Unexpectedly, however, phasic firing patterns during locomotion in rhythmogenic and non-rhythmogenic V2a neurons alike are best explained by distinct modes of synaptic inhibition linked to cell type and speed. At fast speeds reciprocal inhibition in descending V2a neurons supports phasic firing, while recurrent inhibition in bifurcating V2a neurons helps pattern motor output. In contrast, at slow speeds recurrent inhibition in descending V2a neurons supports phasic firing, while bifurcating V2a neurons rely on reciprocal inhibition alone to pattern output. Our findings suggest cell-type-specific, not common, modes of rhythmogenesis generate and coordinate different speeds of locomotion., Competing Interests: MA, SK, DM No competing interests declared, (© 2024, Agha et al.)

Homeostatic plasticity represents a set of mechanisms thought to stabilize some function of neural activity. Here, we identified the specific features of cellular or network activity that were maintained after the perturbation of GABAergic blockade in two different systems: mouse cortical neuronal cultures where GABA is inhibitory and motoneurons in the isolated embryonic chick spinal cord where GABA is excitatory (males and females combined in both systems). We conducted a comprehensive analysis of various spiking activity characteristics following GABAergic blockade. We observed significant variability in many features after blocking GABA A receptors (e.g., burst frequency, burst duration, overall spike frequency in culture). These results are consistent with the idea that neuronal networks achieve activity goals using different strategies (degeneracy). On the other hand, some features were consistently altered after receptor blockade in the spinal cord preparation (e.g., overall spike frequency). Regardless, these features did not express strong homeostatic recoveries when tracking individual preparations over time. One feature showed a consistent change and homeostatic recovery following GABA A receptor block. We found that spike rate within a burst (SRWB) increased after receptor block in both the spinal cord preparation and cortical cultures and then returned to baseline within hours. These changes in SRWB occurred at both single cell and population levels. Our findings indicate that the network prioritizes the burst spike rate, which appears to be a variable under tight homeostatic regulation. The result is consistent with the idea that networks can maintain an appropriate behavioral response in the face of challenges., Competing Interests: Theauthors declare no competing financial interests., (Copyright © 2024 Lakhani et al.)

For most quadrupeds, locomotion involves alternating movements of the fore- and hindlimbs. In birds, however, while walking generally involves alternating movements of the legs, to generate lift and thrust, the wings are moved synchronously with each other. Neural circuits in the spinal cord, referred to as central pattern generators (CPGs), are the source of the basic locomotor rhythms and patterns. Given the differences in the patterns of movement of the wings and legs, it is likely that the neuronal components and connectivity of the CPG that coordinates wing movements differ from those that coordinate leg movements. In this study, we used in vitro preparations of embryonic chicken spinal cords (E11-E14) to compare the neural responses of spinal CPGs that control and coordinate wing flapping with those that control alternating leg movements. We found that in response to N-methyl-D-aspartate (NMDA) or a combination of NMDA and serotonin (5-HT), the intact chicken spinal cord produced rhythmic outputs that were synchronous both bilaterally and between the wing and leg segments. Despite this, we found that this rhythmic output was disrupted by an antagonist of glycine receptors in the lumbosacral (legs), but not the brachial (wing) segments. Thus, our results provide evidence of differences between CPGs that control the wings and legs in the spinal cord of birds., (© 2024. The Author(s).)

Modulation of input from primary afferent fibres has long been examined at the level of the first relays of these fibres. However, recent studies reveal that input to the spinal cord may also be modulated at the level of the very entry of afferent fibres to the spinal grey matter before action potentials in intraspinal collaterals of afferent fibres reach their target neurons. Such modulation greatly depends on the actions of GABA via extrasynaptic membrane receptors. In the reported study we hypothesized that the increase in excitability of afferent fibres following epidural polarization close to the site where collaterals of afferent fibres leave the dorsal columns is due to the release of GABA from two sources: not only GABAergic interneurons but also glial cells. We present evidence, primo, that GABA released from both these sources contributes to a long-lasting increase in the excitability and a shortening of the refractory period of epidurally stimulated afferent fibres and, secondo, that effects of epidural polarization on the release of GABA are more critical for these changes than direct effects of DC on the stimulated fibres. The experiments were carried out in deeply anaesthetized rats in which changes in compound action potentials evoked in hindlimb peripheral nerves by dorsal column stimulation were used as a measure of the excitability of afferent fibres. The study throws new light on the modulation of input to spinal networks but also on mechanisms underlying the restoration of spinal functions., (© 2024 The Author(s). European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background:  We previously reported that normalization of motor evoked potential (MEP) monitoring amplitude by compound muscle action potential (CMAP) after peripheral nerve stimulation prevented the expression of anesthetic fade (AF), suggesting that AF might be due to reduced synaptic transfer in the neuromuscular junction., Methods:  We calculated the time at which AF began for each of craniotomy and spinal cord surgery, and examined whether AF was avoided by CMAP after peripheral nerve stimulation normalization in each. Similar studies were also made with respect to the upper and lower limb muscles., Results:  AF was observed in surgery lasting 160 minutes for craniotomy and 260 minutes or more for spinal surgery, and 195 minutes in the upper limb muscles and 135 minutes in the lower limb muscles. In all the series, AF could be avoided by CMAP after peripheral nerve stimulation normalization., Conclusion:  AF of MEP occurred in both craniotomy and spinal cord surgery, and it was also corrected by CMAP after peripheral nerve stimulation. AF is considered to be mainly due to a decrease in synaptic transfer of the neuromuscular junction due to the accumulation of propofol because of the avoidance by CMAP normalization. However, it may be partially due to a decrease in the excitability of pyramidal tracts and α-motor neurons, because AF occurred earlier in the lower limb muscles than in the upper limb muscles., Competing Interests: None declared., (Thieme. All rights reserved.)

Aim: To study the feasibility of constant dose rate volumetric modulated arc therapy (CDR-VMAT) in radiotherapy for gallbladder cancer by comparing dosimetric parameter suggested by International Commission on Radiation Units and Measurements-83 (ICRU-83) with step and shoot intensity-modulated radiation therapy (SS IMRT). Methods: For this study, we selected 21 post-operative gallbladder cancer patients, which were treated with the IMRT technique from 2016 to 2019. For each patient, we generated SS IMRT plan and CDR-VMAT plan and were dosimetrically compared by parameters suggested by ICRU-83 for PTV. Homogeneity Index (HI) and Conformity Index (CI) were also calculated. For evaluation of Organ at Risk (OAR), we compared the mean doses, volume doses to the right kidney, left kidney, both kidneys combined, liver and max dose to the spinal cord. Monitor units (MUs) and treatment delivery time were also compared. Results: On comparing, we found that CDR-VMAT plans were highly conformed as CI and PCI (CI define by Paddick) were found more (0·98 ± 0·01 vs. 0·97 ± 0·03 and 0·86 ± 0·05 vs. 0·85 ± 0·05) than IMRT plans but not statistically significant. Better dose HI was found for IMRT plans with statistical significant difference (p < 0·001). The tumour coverage was found similar 98·24% and 97·83% for SS IMRT and CDR-VMAT, respectively. For D2%, the maximum dose to PTV was significantly lower in IMRT (p = 0·001). D50% and mean dose to PTV were also comparable to IMRT with no statistically significant difference. The OAR parameters were comparable in both the techniques. The mean doses and volume doses V10, V20 and V30 to the right kidney, left kidney and liver were also comparable with no significant difference (p > 0·05) was noted among them. However, the maximum dose to the spinal cord was significantly less in CDR-VMAT (21·1 Gy vs. 25·1Gy) than SS IMRT with p = 0·006. More MUs were associated with the CDR-VMAT technique, but shorter treatment delivery time than the IMRT technique. Conclusions: On dosimetric comparison of two treatment techniques, we conclude that CDR-VMAT can be a valid option in radiotherapy as it achieved highly conformed dose distribution, comparable tumour coverage and OAR sparing as IMRT technique for gallbladder cancer. [ABSTRACT FROM AUTHOR]