Functional near-infrared spectroscopy in non-invasive neuromodulation

Non-invasive cerebral neuromodulation technologies are essential for the reorganization of cerebral neural networks,which have been widely applied in the field of central neurological diseases,such as stroke,Parkinson’s disease,and mental disorders.Although significant advances have been made in neuromodulation technologies,the identification of optimal neurostimulation paramete rs including the co rtical target,duration,and inhibition or excitation pattern is still limited due to the lack of guidance for neural circuits.Moreove r,the neural mechanism unde rlying neuromodulation for improved behavioral performance remains poorly understood.Recently,advancements in neuroimaging have provided insight into neuromodulation techniques.Functional near-infrared spectroscopy,as a novel non-invasive optical brain imaging method,can detect brain activity by measuring cerebral hemodynamics with the advantages of portability,high motion tole rance,and anti-electromagnetic interference.Coupling functional near-infra red spectroscopy with neuromodulation technologies offe rs an opportunity to monitor the cortical response,provide realtime feedbac k,and establish a closed-loop strategy integrating evaluation,feedbac k,and intervention for neurostimulation,which provides a theoretical basis for development of individualized precise neuro rehabilitation.We aimed to summarize the advantages of functional near-infra red spectroscopy and provide an ove rview of the current research on functional near-infrared spectroscopy in transcranial magnetic stimulation,transcranial electrical stimulation,neurofeedback,and braincomputer interfaces.Furthermore,the future perspectives and directions for the application of functional near-infrared spectroscopy in neuromodulation are summarized.In conclusion,functional near-infrared spectroscopy combined with neuromodulation may promote the optimization of central pellral reorganization to achieve better functional recovery form central nervous system diseases.

Electrical neuromodulation therapy for inflammatory bowel disease

Inflammatory bowel disease(IBD)is an inflammatory disease of the gastrointestinal(GI)tract.It has financial and quality of life impact on patients.Although there has been a significant advancement in treatments,a considerable number of patients do not respond to it or have severe side effects.Therapeutic approaches such as electrical neuromodulation are being investigated to provide alternate options.Although bioelectric neuromodulation technology has evolved significantly in the last decade,sacral nerve stimulation(SNS)for fecal incontinence remains the only neuromodulation protocol commonly utilized use for GI disease.For IBD treatment,several electrical neuromodulation techniques have been studied,such as vagus NS,SNS,and tibial NS.Several animal and clinical experiments were conducted to study the effectiveness,with encouraging results.The precise underlying mechanisms of action for electrical neuromodulation are unclear,but this modality appears to be promising.Randomized control trials are required to investigate the efficacy of intrinsic processes.In this review,we will discuss the electrical modulation therapy for the IBD and the data pertaining to it.

Multimodal treatment for spinal cord injury: a sword of neuroregeneration upon neuromodulation

Spinal cord injury is linked to the interruption of neural pathways,which results in irreversible neural dysfunction.Neural repair and neuroregeneration are critical goals and issues for rehabilitation in spinal cord injury,which require neural stem cell repair and multimodal neuromodulation techniques involving personalized rehabilitation strategies.Besides the involvement of endogenous stem cells in neurogenesis and neural repair,exogenous neural stem cell transplantation is an emerging effective method for repairing and replacing damaged tissues in central nervous system diseases.However,to ensure that endogenous or exogenous neural stem cells truly participate in neural repair following spinal cord injury,appropriate interventional measures(e.g.,neuromodulation)should be adopted.Neuromodulation techniques,such as noninvasive magnetic stimulation and electrical stimulation,have been safely applied in many neuropsychiatric diseases.There is increasing evidence to suggest that neuromagnetic/electrical modulation promotes neuroregeneration and neural repair by affecting signaling in the nervous system;namely,by exciting,inhibiting,or regulating neuronal and neural network activities to improve motor function and motor learning following spinal cord injury.Several studies have indicated that fine motor skill rehabilitation training makes use of residual nerve fibers for collateral growth,encourages the formation of new synaptic connections to promote neural plasticity,and improves motor function recovery in patients with spinal cord injury.With the development of biomaterial technology and biomechanical engineering,several emerging treatments have been developed,such as robots,brain-computer interfaces,and nanomaterials.These treatments have the potential to help millions of patients suffering from motor dysfunction caused by spinal cord injury.However,large-scale clinical trials need to be conducted to validate their efficacy.This review evaluated the efficacy of neural stem cells and magnetic or electrical stimulation combined with rehabilitation training and intelligent therapies for spinal cord injury according to existing evidence,to build up a multimodal treatment strategy of spinal cord injury to enhance nerve repair and regeneration.

Clinical outcomes of sacral neuromodulation in non-neurogenic,non-obstructive dysuria:A 5-year retrospective,multicentre study in China

BACKGROUND Management of non-neurogenic,non-obstructive dysuria represents one of the most challenging dilemmas in urological practice.The main clinical symptom is the increase in residual urine.Voiding dysfunction is the main cause of dysuria or urinary retention,mainly due to the decrease in bladder contraction(the decrease in contraction amplitude or duration)or the increase in outflow tract resistance.Sacral neuromodulation(SNM)has been used for>10 years to treat many kinds of lower urinary tract dysfunction.It has become increasingly popular in China in recent years.Consequently,studies focusing on nonneurogenic,non-obstructive dysuria patients treated by SNM are highly desirable.AIM To assess the outcome of two-stage SNM in non-neurogenic,non-obstructive dysuria.METHODS Clinical data of 54 patients(26 men,28 women)with non-neurogenic,nonobstructive dysuria treated by SNM from January 2012 to December 2016 in ten medical centers in China were retrospectively analyzed.All patients received two or more conservative treatments.The voiding diary,urgency score,and quality of life score before operation,after implantation of tined lead in stage I(test period),and during short-term follow-up(latest follow-up)after implantation of the implanted pulse generator in stage II were compared to observe symptom improvements.RESULTS Among the 54 study patients,eight refused to implant an implanted pulse generator because of the unsatisfactory effect,and 46 chose to embed the implanted pulse generator at the end of stage I.The conversion rate of stage I to stage II was 85.2%.The average follow-up time was 18.6 mo.There were significant differences between baseline(before stage I)and the test period(after stage I)in residual urine,voiding frequency,average voiding amount,maximum voiding amount,nocturia,urgency score,and quality of life score.The residual urine and urgency score between the test period and the latest follow-up time(after stage II)were also significantly different.No significant differences were observed for other parameters.No wound infection,electrode breakage,or other irreversible adverse events occurred.CONCLUSION SNM is effective for patients with non-neurogenic,non-obstructive dysuria showing a poor response to traditional treatment.The duration of continuous stimulation may be positively correlated with the improvement of residual urine.

Neuromodulation for fecal incontinence: An effective surgical intervention

Fecal incontinence is a disabling symptom with medical and social implications,including fear,embarrassment,isolation and even depression.Most patients live in seclusion and have to plan their life around the symptom,with secondary impairment of their quality of life.Conservative management and biofeedback therapy are reported to benefit a good percentage of those affected.However,surgery must be considered in the nonresponder population.Recently,sacral nerve electrostimulation,lately named neuromodulation,has been reported to benefit patients with fecal incontinence in randomized controlled trials more than placebo stimulation and conservative management,by some unknown mechanism.Neuromodulation is a minimally invasive procedure with a low rate of adverse events and apparently favorable cost-efficacy profile.This review is intended to expand knowledge about this effective intervention among the non-surgically skilled community who deals with this disabled group of patients.

The role of gap junctions in cell death and neuromodulation in the retina

Vision altering diseases,such as glaucoma,diabetic retinopathy,age-related macular degeneration,myopia,retinal vascular disease,traumatic brain injuries and others cripple many lives and are projected to continue to cause anguish in the foreseeable future.Gap junctions serve as an emerging target for neuromodulation and possible regeneration as they directly connect healthy and/or diseased cells,thereby playing a crucial role in pathophysiology.Since they are permeable for macromolecules,able to cross the cellular barriers,they show duality in illness as a cause and as a therapeutic target.In this review,we take recent advancements in gap junction neuromodulation(pharmacological blockade,gene therapy,electrical and light stimulation)into account,to show the gap junction’s role in neuronal cell death and the possible routes of rescuing neuronal and glial cells in the retina succeeding illness or injury.

Acupuncture as a bioinformatics science and a proposal for the recognition of a new law of nature “Law of therapeutic neuromodulation”

Brain, an organ similar to a computer, is the ultimate director of the body1. This means that organs, tissues and cells are under its control and that these parts of the body do not control what happen to them. If the brain is functioning properly, we have health;and if it works wrongly a disease will show. Acting on the brain by neuromodulation, by means of acupuncture, homeopathy or even allopathic drugs can produce a therapeutic response. The purpose of this paper is to recognize this effect and propose a new Law of Cure which explains how several complementary and alternative medicine (CAM) systems work. In this theory, acupuncture works by stimulating peripheral sensory receptors and transmitting information to the brain which in turn will trigger a curative response to the affected organ. In this sense, acupuncture is an informatics system for a biological system, and therefore it could be considered part of the bioinformatics sciences, in the same idea that the brain is a living computer which has inputs and outputs and controls all process inside the body. In this paper we present the basis for this theory.

2008中国神经调控研讨会(Chinese Neuromodulation Conference)会议通知

由中国医师协会神经外科医师分会与中国神经调控专业委员会筹委会共同主办的第二届中国神经调控研讨会(Chinese Neuromodulation Conference)将于2008年10月24日在河北省石家庄召开。大会特邀请了希腊著名神经外科教授Damianos E.Sakas、Robert Levy及国内各领域专家作专题讲座。此次会议将为神经内、外科、心内科、疼痛科、麻醉科、生物工程。

Sacral neuromodulation therapy of the lower urinary tract: A review of the literature and unanswered questions

Objective: To review the evidence surrounding Sacral Neuromodulation therapy and delineate areas that will need more research. Methods: An extensive search was performed on the available literature on SNM for lower urinary tract dysfunction. Based on the results of the search, the mechanisms of action, indications, technique, and patient characteristics of therapy failures and success are presented and discussed. Results: SNM is accepted by the FDA since 1997 for the treatment of lower urinary tract dysfunction. As it is a relatively new procedure, there are variations in the technique of lead placement, generator choice, testing interval, patient selection, time to explantation, and definitions of therapy failures and successes. Conclusions: SNM is a safe and therapeutic option for the treatment of urgencyfrequency syndrome, urge incontinence, and idiopathic urinary retention. However, there are multiple unanswered questions that require extensive research.

Modulated-Power Implantable Neuromodulation Devices and Their Impact on Surrounding Tissue Temperatures

This project was intended to determine whether the preprogrammed time-varying recharge protocol for a battery incased in a neuromodulation implant can give rise to tissue temperatures that surpass a safe level or are otherwise benign. The study included the development of a highly accurate model of all the thermal processes that are activated by the recharging of the battery contained within the neuromodulation implant. The model was implemented by numerical simulations performed for several realistic operating conditions. The computed spatial and temporal tissue temperature distributions were employed to estimate possible tissue damage by making use of two independent methodologies. Independent calorimeter-based experiments were performed to provide validation for the calculated rates of heat generation in the coils of the implant. Spatial and temporal tissue temperature distributions extracted from the numerical simulations revealed the thermal effects associated with several realistic operating protocols. None of the operating protocols gave rise to temperatures above 42℃. Numerical values of thermal tissue damage metrics were determined and compared with accepted values which correspond to the absence and the presence of tissue damage. The experimentally determined rate of heat generation in the implant coils validated that from electrical measurements to within 2%. Both the tissue temperature results and the thermal damage metrics found no evidence of tissue injury when time-varying preprogrammed protocols are used in the recharging of neuromodulation implant-encased batteries.

Bioinspired nanotransducers for neuromodulation

The field of neuromodulation has experienced significant advancements in the past decade,owing to breakthroughs in disciplines such as materials science,genetics,bioengineering,photonics,and beyond.The convergence of these fields has resulted in the development of nanotransducers,devices that harness the synergies of these diverse disciplines.These nanotransducers,essential for neuromodulation,often draw inspiration from energy conversion processes found in nature for their unique modalities.In this review,we will delve into the latest advancements in wireless neuromodulation facilitated by optical,magnetic,and mechanical nanotransducers.We will examine their working principles,properties,advantages,and limitations in comparison to current methods for deep brain neuromodulation,highlighting the impact of natural systems on their design and functionality.Additionally,we will underscore potential future directions,emphasizing how continued progress in materials science,neuroscience,and bioengineering might expand the horizons of what is achievable with nanotransducer-enabled neuromodulation.

Individualized brain mapping for navigated neuromodulation

The brain is a complex organ that requires precise mapping to understand its structure and function.Brain atlases provide a powerful tool for studying brain circuits,discovering biological markers for early diagnosis,and developing personalized treatments for neuropsychiatric disorders.Neuromodulation techniques,such as transcranial magnetic stimulation and deep brain stimulation,have revolutionized clinical therapies for neuropsychiatric disorders.However,the lack of fine-scale brain atlases limits the precision and effectiveness of these techniques.Advances in neuroimaging and machine learning techniques have led to the emergence of stereotactic-assisted neurosurgery and navigation systems.Still,the individual variability among patients and the diversity of brain diseases make it necessary to develop personalized solutions.The article provides an overview of recent advances in individualized brain mapping and navigated neuromodulation and discusses the methodological profiles,advantages,disadvantages,and future trends of these techniques.The article concludes by posing open questions about the future development of individualized brain mapping and navigated neuromodulation.

Millimetric devices for nerve stimulation:a promising path towards miniaturization

Nerve stimulation is a rapidly developing field,demonstrating positive outcomes across several conditions.Despite potential benefits,current nerve stimulation devices are large,complicated,and are powered via implanted pulse generators.These facto rs necessitate invasive surgical implantation and limit potential applications.Reducing nerve stimulation devices to millimetric sizes would make these interventions less invasive and facilitate broader therapeutic applications.However,device miniaturization presents a serious engineering challenge.This review presents significant advancements from several groups that have overcome this challenge and developed millimetricsized nerve stimulation devices.These are based on antennas,mini-coils,magneto-electric and optoelectronic materials,or receive ultrasound power.We highlight key design elements,findings from pilot studies,and present several considerations for future applications of these devices.

Age-related driving mechanisms of retinal diseases and neuroprotection by transcription factor EB-targeted therapy

Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.

Progress in neurorehabilitation research and the support by the National Natural Science Foundation of China from 2010 to 2022

The National Natural Science Foundation of China is one of the major funding agencies for neuro rehabilitation research in China.This study reviews the frontier directions and achievements in the field of neurorehabilitation in China and wo rldwide.We used data from the Web of Science Core Collection(WoSCC) database to analyze the publications and data provided by the National Natural Science Foundation of China to analyze funding information.In addition,the prospects for neurorehabilitation research in China are discussed.From 2010 to 2022,a total of 74,220 publications in neurorehabilitation were identified,with there being an overall upward tendency.During this period,the National Natural Science Foundation of China has funded 476 research projects with a total funding of 192.38 million RMB to support neuro rehabilitation research in China.With the support of the National Natural Science Foundation of China,China has made some achievements in neurorehabilitation research.Research related to neurorehabilitation is believed to be making steady and significant progress in China.

Cortico-striatal gamma oscillations are modulated by dopamine D3 receptors in dyskinetic rats

Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.

Transcranial direct current stimulation efficacy in trigeminal neuralgia

Trigeminal neuralgia is a severe,disabling pain and its deafferentation remains a challenge for health providers.Transcranial direct current stimulation is a non-invasive stimulation technique which finds new utility in managing pain.There-fore,the introduction of alternative,non-invasive,safe,and effective methods should be considered in treating patients with trigeminal neuralgia unresponsive to conventional treatment.

Effect of transcranial direct current stimulation on supernumerary phantom limb pain in spinal cord injured patient:A case report

BACKGROUND Supernumerary phantom limb(SPL)sensation is the experience of additional limbs,either single or a pair of limbs.Unique to traumatic spinal cord injuries,we report effect of transcranial direct current stimulation(tDCS)on SPL pain in a patient with cervical cord injury.CASE SUMMARY The subject was a 57-year-old man who was diagnosed with complete spinal cord injury(C6/C5,motor level;C5/C5,sensory level;AIS-A)approximately three months ago.After a period of 2 wk,we administered anodal tDCS over the motor cortex for 15 minutes at an intensity of 1.5 mA.Following that treatment,the patient experienced a decrease of SPL pain intensity and frequency,which lasted for 1 week after the end of treatment.CONCLUSION Targeting the motor cortex through neuromodulation appears to be a promising option for the management of SPL pain.

Outcomes and efficacy of magnetic resonance imaging-compatible sacral nerve stimulator for management of fecal incontinence: A multi-institutional study

BACKGROUND Fecal incontinence(FI)is an involuntary passage of fecal matter which can have a significant impact on a patient’s quality of life.Many modalities of treatment exist for FI.Sacral nerve stimulation is a well-established treatment for FI.Given the increased need of magnetic resonance imaging(MRI)for diagnostics,the In-terStim which was previously used in sacral nerve stimulation was limited by MRI incompatibility.Medtronic MRI-compatible InterStim was approved by the United States Food and Drug Administration in August 2020 and has been widely used.AIM To evaluate the efficacy,outcomes and complications of the MRI-compatible InterStim.METHODS Data of patients who underwent MRI-compatible Medtronic InterStim placement at UPMC Williamsport,University of Minnesota,Advocate Lutheran General Hospital,and University of Wisconsin-Madison was pooled and analyzed.Patient demographics,clinical features,surgical techniques,complications,and outcomes were analyzed.Strengthening the Reporting of Observational studies in Epidemiology(STROBE)cross-sectional reporting guidelines were used.RESULTS Seventy-three patients had the InterStim implanted.The mean age was 63.29±12.2 years.Fifty-seven(78.1%)patients were females and forty-two(57.5%)patients had diabetes.In addition to incontinence,overlapping symptoms included diarrhea(23.3%),fecal urgency(58.9%),and urinary incontinence(28.8%).Fifteen(20.5%)patients underwent Peripheral Nerve Evaluation before proceeding to definite implant placement.Thirty-two(43.8%)patients underwent rechargeable InterStim placement.Three(4.1%)patients needed removal of the implant.Migration of the external lead connection was observed in 7(9.6%)patients after the stage I procedure.The explanation for one patient was due to infection.Seven(9.6%)patients had other complications like nerve pain,hematoma,infection,lead fracture,and bleeding.The mean follow-up was 6.62±3.5 mo.Sixty-eight(93.2%)patients reported significant improvement of symptoms on follow-up evaluation.CONCLUSION This study shows promising results with significant symptom improvement,good efficacy and good patient outcomes with low complication rates while using MRI compatible InterStim for FI.Further long-term follow-up and future studies with a larger patient population is recommended.

Effects of Appropriate Prolonged Sacral Neuromodulation Testing in Improving Implantation Rate of a Permanent Implantable Pulse Generator in Patients with Refractory Lower Urinary Tract Dysfunctions in China's Mainland

Background： Sacral neuromodulation （SNM） has become an effective method for treating lower urinary tract voiding dysfunction during the past 20 years. Because of the expensive cost, the number of implantable pulse generator （IPG） implantations per year in China is far lower than that in Western developed countries since 2012. This study was to summarize the effects of the appropriate prolonged SNM testing time in improving the implantation rate of a permanent IPG in patients with refractory lower urinary tract symptoms （LUTS） in China's Mainland. Methods： From January 2013 to June 2016, 51 patients with refractory LUTS received SNM therapy, in this study, we compared the conversion rate 2 weeks after the Stage I test and final actual conversion rate. We also observed the complications （such as pain, infection, and electrode displacement） and effectiveness. We tried to improve an appropriate prolonged test time which was favorable for improving the SNM conversion rate while ensuring safety and effectiveness. Results： Among 51 patients receiving SNM therapy, 19 patients （mean age 45.0 ±16.9 years） had poor Stage I test results, and on an average, the electrode was removed 27.4 ± 9.6 days after the surgery. In one patient, the electrode was removed within 2 weeks; when the remaining 18 patients were questioned 2 weeks after testing, none of the patients wanted to terminate the test, and all the 18 patients desired to prolong the testing time to further observe the treatment effect. The remaining 32 patients （mean age 46.7 ± 15.3 years） received Stage If permanent implantation at 19.6 ± 10.4 days after the surgery. The overall Stage Ⅰ-Ⅱ conversion was 62.7% （32/51） in this study. Within 2 weeks after the surgery, only eight patients received Stage II permanent implantation, and the conversion rate was only 15.7% （8/51 ）, which was much lower than the overall conversion rate of 62.7%. Nearly 84.4% （27/32） of the patients received Stage 11 implantation within 4 weeks. None of the patients had incision infections. In one patient, the entire system was removed 1 month after Stage II implantation due to pain in the implantation site. Conclusions： Appropriate extension of the Stage I testing time of an SNM-barbed electrode could significantly improve the Stage II permanent implantation rate in Chinese refractory LUTS patients; there were no wound infections, and the postoperative complication rate was low. This study recommended that Stage I period of SNM therapy should be 4 weeks according to safety and successful conversion rate.