scholarly journals Detection of Small Fiber Neuronal Activity with Optically Pumped Magnetometers

2021 ◽  
Author(s):  
Yifeng Bu ◽  
Amir Borna ◽  
Peter Schwindt ◽  
Xiangen Zeng ◽  
Mingxiong Huang ◽  
...  

The pain experience is a complex process that involves the activation of multiple neuronal signaling pathways that originate in the peripheral nervous system and are transmitted to the central nervous system. In the peripheral nervous system, specialized peripheral nociceptor (unmyelinated C fibers and lightly myelinated A-Delta; fibers) depolarization results in afferent transmission of noxious signals. Small Fiber Neuropathy (SFN) can result in chronic neuropathic pain with significant lifetime morbidity if not promptly treated. Current technological and operator limitations may delay SFN diagnosis and prolong appropriate treatment. Therefore, there is an unmet need for robust and non-invasive ways to accurately measure small fiber function. It is well known that the propagation of action potentials along a nerve is the result of ionic current flow which, according to the Ampere Law, generates a small magnetic field that is detectable by magnetometers such as superconducting quantum interference device (SQUID) Magnetoencephalography (MEG) systems. Optically pumped magnetometers (OPM) are an emerging class of quantum magnetic sensors with a demonstrated sensitivity of 1 fT/SQRT;Hz level, capable of cortical action potential detection. However, they have not as of yet been implemented for peripheral nerve action potential detection. We demonstrate for the first time, compelling evidence that OPM can detect the magnetic signature of travelling peripheral nerve action potentials that indicate OPM use as a potential technique for SFN diagnosis.

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 37-37
Author(s):  
Kristin Komnick ◽  
Jennifer May ◽  
Pouneh Kermani ◽  
Sreemanti Basu ◽  
Irene Hernandez ◽  
...  

Blood cell production is regulated by peripheral nerve fibers that innervate the bone marrow. However, little is known about the development or maintenance of hematopoietic innervation. Schwann cells (SCs) are the primary axon 'support cells' of the peripheral nervous system (PNS), and abnormal SC development is sufficient to impair peripheral nerve function. SCs are also the primary repair cell for the PNS which makes them an attractive therapeutic target for normalization of drug or malignancy-induced 'hematopoietic neuropathy'. We hypothesized that neural regulation of hematopoiesis is dependent on SC development. To test this hypothesis, we used the Myelin Protein Zero-Cre (MP0-Cre); Lamc1fl/fl mouse line in which laminin-γ1 expression is deleted from SC precursors and their progeny1. Early SC maturation is dependent on autocrine SC precursor-derived molecules such as laminin-γ1. SC differentiation arrests prior to axon sorting and ensheathment in MP0-Cre; Lamc1fl/fl mice, and causes a global peripheral neuropathy that persists throughout the lifetime of the animal. Preliminary hematopoietic analysis of 'steady state' MP0-Cre; Lamc1fl/fl and littermate control mice has shown the following: (1) MP0-Cre; Lamc1fl/fl bone marrow is innervated, and Cre-mediated gene recombination occurs in cells immunophenotypically consistent with SCs throughout the peripheral nervous system, including those in the bone marrow; (2) MP0-Cre; Lamc1fl/fl mice are lymphopenic but not neutropenic; (3) MP0-Cre; Lamc1fl/fl mice have significantly reduced spleen size and cellularity; and (4) MP0-Cre; Lamc1fl/fl bone marrow has an ~50% reduction in Lin-Sca-1+Kit+(LSK) cells (measured as a percentage of the Lin- compartment of the bone marrow). These results are consistent with earlier work by our groups in which we found that global Lamc1 gene deletion in adult mice induced peripheral blood lymphopenia, reduced spleen size, and a niche-dependent reduction of lymphoid progenitor and precursor cells that was secondary to increased lymphoid precursor cell apoptosis and reduced proliferation (UBC-CreERT2; Lamc1fl/fl mouse line). As with the SC-specific laminin-γ1 deficient mice, myelopoiesis was preserved in the UBC-CreERT2; Lamc1fl/fl mice. Based on results from MP0-Cre; Lamc1fl/fl and UBC-CreERT2; Lamc1fl/fl mice, we conclude that early lymphoid but not myeloid development requires laminin-γ1 expression by MP0-Cre-targetted niche cells, i.e. Schwann Cells. Our results are consistent with reports from other labs that hematopoietic sympathetic neuropathy promotes aberrant myeloid expansion at the expense of lymphopoiesis2. Going forward, we will determine whether lymphopoietic development is dependent on global versus laminin-specific SC-derived cues, and whether these signals are transmitted directly between SCs and lymphoid biased HSPCs or indirectly via other components of the hematopoietic niche. We anticipate that this line of investigation will provide molecular insights and pharmacologic targets for prevention and or normalization of the 'hematopoietic neuropathy' induced by diabetes, aging, neurotoxic chemotherapies and myeloid malignancies. REFERENCES: 1 Yu, W. M., Feltri, M. L., Wrabetz, L., Strickland, S. & Chen, Z. L. Schwann cell-specific ablation of laminin gamma1 causes apoptosis and prevents proliferation. J Neurosci25, 4463-4472, doi:10.1523/JNEUROSCI.5032-04.2005 (2005). 2 Maryanovich, M. et al. Adrenergic nerve degeneration in bone marrow drives aging of the hematopoietic stem cell niche. Nat Med24, 782-791, doi:10.1038/s41591-018-0030-x (2018). Disclosures No relevant conflicts of interest to declare.


Author(s):  
Robert J. Spinner

Peripheral nerve is an important and historical part of neurosurgery. It also has been a major focus of both the written and oral examinations administered by the American Board of Neurological Surgeons (ABNS). The Oral Board candidate must be prepared for potentially one to several questions on some of the common disorders of the peripheral nervous system. In this chapter, a systematic approach to peripheral nerve problems is presented. Common areas that might be examined include tumors, injuries, inflammatory conditions, entrapments, and neuropathic pain. Five cases are illustrated, and “pearls” are provided. At the conclusion of the chapter are nine photographs representing problems the Oral Board candidate should be able to identify and answer.


Neurosurgery ◽  
2009 ◽  
Vol 65 (suppl_4) ◽  
pp. A153-A159 ◽  
Author(s):  
Martijn J.A. Malessy ◽  
Willem Pondaag ◽  
J. Gert van Dijk

Abstract OBJECTIVE Obstetric brachial plexus lesions (OBPLs) are caused by traction to the brachial plexus during labor. Typically, in these lesions, the nerves are usually not completely ruptured but form a “neuroma-in-continuity.” Even in the most severe OBPL lesions, at least some axons will pass through this neuroma-in-continuity and reach the tubes distal to the lesion site. These axons may be particularly prone to abnormal branching and misrouting, which may explain the typical feature of co-contraction. An additional factor that may reduce functional regeneration is that improper central motor programming may occur. Surgery should be restricted to severe cases in which spontaneous restoration of function will not occur, i.e., in neurotmesis or root avulsions. A major problem is how to predict whether function will be best after spontaneous nerve outgrowth or after nerve reconstructive surgery. When a decision has been made to perform an early surgical exploration, what to do with the neuroma-in-continuity can be a problem. The intraoperative appraisal is difficult and depends on experience, but even in experienced hands, misjudgment can be made. METHODS We performed an observational study to assess whether early electromyography (at the age of 1 month) is able to predict severe lesions. Additionally, the value of intraoperative nerve action potential and compound motor action potentials was investigated. RESULTS Severe cases of OBPL can be identified at 1 month of age on the basis of clinical findings and needle electromyography of the biceps. This outcome needs independent validation, which is currently in progress. Nerve action potential and compound motor action potential recordings show statistically significant differences on the group level between avulsion, neurotmesis, axonotmesis, and normal. For the individual patient, a clinically useful cutoff point could not be found. Intraoperative nerve action potential and compound motor action potential recordings do not add to the decision making during surgery. CONCLUSION The absence of a “gold standard” for the assessment of the severity of the OBPL lesion makes prognostic studies of OBPL complex. The currently available assessment strategies used to obtain the best possible solutions are discussed.


2017 ◽  
Author(s):  
Kim I Chisholm ◽  
Nikita Khovanov ◽  
Douglas M Lopes ◽  
Federica La Russa ◽  
Stephen B McMahon

AbstractGreater emphasis on the study of intact cellular networks in their physiological environment has led to rapid advances in intravital imaging in the central nervous system, while the peripheral system remains largely unexplored. To assess large networks of sensory neurons we selectively label primary afferents with GCaMP6s and visualise their functional responses in vivo to peripheral stimulation. We show that we are able to monitor simultaneously the activity of hundreds of sensory neurons with sensitivity sufficient to detect, in most cases, single action potentials with a typical rise time of around 200 milliseconds, and an exponential decay with a time constant of approximately 700 milliseconds. Using this sensitive technique we are able to show that large scale recordings demonstrate the recently disputed polymodality of nociceptive primary afferents with between 40-80% of thermally sensitive DRG neurons responding also to noxious mechanical stimulation. We also specifically assess the small population of peripheral cold fibres and demonstrate significant sensitisation to cooling after a model of sterile and persistent inflammation, with significantly increased sensitivity already at decreases of 5°C when compared to uninflamed responses. This not only reveals interesting new insights into the (patho)physiology of the peripheral nervous system but also demonstrates the sensitivity of this imaging technique to physiological changes in primary afferents.Significance StatementMost of our functional understanding of the peripheral nervous system has come from single unit recordings. However, the acquisition of such data is labour-intensive and usually ‘low yield’. Moreover, some questions are best addressed by studying populations of neurons. To this end we report on a system that monitors activity in hundreds of single sensory neurons simultaneously, with sufficient sensitivity to detect in most cases single action potentials. We use this technique to characterise nociceptor properties and demonstrate polymodality in the majority of neurons and their sensitization under inflammatory conditions. We therefore believe this approach will be very useful for the studies of the somatosensory system in general and pain in particular.


Innova ◽  
2020 ◽  
pp. 26-28
Author(s):  
Бородина К.А. ◽  
Затолокина М.А. ◽  
Харченко В.В. ◽  
Затолокина М.А. ◽  
Мишина Е.С. ◽  
...  

Currently, there is a lot of literature and research that reflects data on the structure of the peripheral nervous system. However, it should be noted that the results available in the sources do not contain a full range of data on the structural features of paraneural structures and have some contradictions. In addition, data on the morphological features of the structure of the paranephrium of peripheral nerves in ontogenesis are practically absent. This was the beginning of our research, in order to obtain new, more in-depth data on the age-related variability of the peripheral nerve paraneurium.


Author(s):  
Tim Godel ◽  
Philipp Bäumer ◽  
Said Farschtschi ◽  
Klaus Püschel ◽  
Barbara Hofstadler ◽  
...  

Abstract Purpose To examine long-term alterations of the dorsal root ganglia (DRG) and the peripheral nerve in patients with neurofibromatosis type 2 (NF2) by in vivo high-resolution magnetic resonance neurography (MRN) and their correlation to histology. Methods In this prospective study the lumbosacral DRG, the right sciatic, tibial, and peroneal nerves were examined in 6 patients diagnosed with NF2 and associated polyneuropathy (PNP) by a standardized MRN protocol at 3 T. Volumes of DRG L3–S2 as well as peripheral nerve lesions were assessed and compared to follow-up examinations after 14–100 months. In one patient, imaging findings were further correlated to histology. Results Follow-up MRN examination showed a non-significant increase of volume for the DRG L3: +0.41% (p = 0.10), L4: +22.41% (p = 0.23), L5: +3.38% (p = 0.09), S1: +10.63% (p = 0.05) and S2: +1.17% (p = 0.57). Likewise, peripheral nerve lesions were not significantly increased regarding size (2.18 mm2 vs. 2.15 mm2, p = 0.89) and number (9.00 vs. 9.33, p = 0.36). Histological analyses identified schwannomas as the major correlate of both DRG hyperplasia and peripheral nerve lesions. For peripheral nerve microlesions additionally clusters of onion-bulb formations were identified. Conclusion Peripheral nervous system alterations seem to be constant or show only a minor increase in adult NF2. Thus, symptoms of PNP may not primarily attributed to the initial schwannoma growth but to secondary long-term processes, with symptoms only occurring if a certain threshold is exceeded. Histology identified grouped areas of Schwann cell proliferations as the correlate of DRG hyperplasia, while for peripheral nerve lesions different patterns could be found.


2020 ◽  
Vol 24 (02) ◽  
pp. 175-180
Author(s):  
Alberto Stefano Tagliafico ◽  
Raquel Prada González ◽  
Federica Rossi ◽  
Bianca Bignotti ◽  
Carlo Martinoli

AbstractThe peripheral nervous system is increasingly being investigated using medical imaging as a complement or in association with electrodiagnostics tests. The application of imaging techniques, such as ultrasound (US) and magnetic resonance imaging (MRI), allows detailed visualization of the peripheral nervous system. According to the European Society of Musculoskeletal Radiology, the use of US for nerve evaluation is strongly encouraged. In addition, the role of US is further enhanced by the wide application of US-guided techniques to diagnose or to treat peripheral nerve disorders.Standard evaluation of peripheral nerves on US usually relies on cross-sectional area evaluation with different cutoff values in the osteofibrous tunnels and outside them. In several anatomical areas, side-to-side comparison is highly recommended because it helps distinguish subtle variations by using the unaffected limb as an internal control.US is widely used to perform US-guided interventional procedures on peripheral nerves. The recent development of radiomics and machine and deep learning applied to peripheral nerves may reveal new insights beyond the capabilities of the human eye. Radiomics may have a role in expanding the diagnostic capabilities of US and MRI in the study of peripheral nerve pathology, especially when the cross-sectional area is not markedly increased.


1987 ◽  
Vol 96 (1) ◽  
pp. 99-105 ◽  
Author(s):  
Scott D. Spagnoli ◽  
James C. Saunders

Chronic electrodes, placed on the round windows of four adult chinchillas, were used to measure whole-nerve action potential (AP) thresholds and tuning curves. The AP quiet thresholds were within 17 dB of thresholds measured by behavioral methods and within 3 dB of those measured by other evoked response procedures. The AP tuning curves, obtained by a simultaneous masking procedure, were also similar to previously measured tuning curves in the chinchilla. These results indicate that long-term indwelling electrodes can be successfully placed on the chinchilla round window and used to measure threshold sensitivity and frequency selectivity. Recordings from these electrodes could be used in a variety of situations and may be particularly useful in studying the effects of noise on the cochlea.


2002 ◽  
Vol 283 (3) ◽  
pp. H1031-H1041 ◽  
Author(s):  
Gui-Rong Li ◽  
Chu-Pak Lau ◽  
Anique Ducharme ◽  
Jean-Claude Tardif ◽  
Stanley Nattel

Heart failure (HF) produces important alterations in currents underlying cardiac repolarization, but the transmural distribution of such changes is unknown. We therefore recorded action potentials and ionic currents in cells isolated from the endocardium, midmyocardium, and epicardium of the left ventricle from dogs with and without tachypacing-induced HF. HF greatly increased action potential duration (APD) but attenuated APD heterogeneity in the three regions. Early afterdepolarizations (EADs) were observed in all cell types of failing hearts but not in controls. Inward rectifier K+ current ( I K1) was homogeneously reduced by ∼41% (at −60 mV) in the three cell types. Transient outward K+ current ( I to1) was decreased by 43–45% at +30 mV, and the slow component of the delayed rectifier K+ current ( I Ks) was significantly downregulated by 57%, 49%, and 58%, respectively, in epicardial, midmyocardial, and endocardial cells, whereas the rapid component of the delayed rectifier K+ current was not altered. The results indicate that HF remodels electrophysiology in all layers of the left ventricle, and the downregulation of I K1, I to1, and I Ks increases APD and favors occurrence of EADs.


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