Double-target neural circuit-magnetic stimulation improves motor function in spinal cord injury by attenuating astrocyte activation

Multi-target neural circuit-magnetic stimulation has been clinically shown to improve rehabilitation of lower limb motor function after spinal cord injury. However, the precise underlying mechanism remains unclear. In this study, we performed double-target neural circuit-magnetic stimulation on the left motor cortex and bilateral L5 nerve root for 3 successive weeks in a rat model of incomplete spinal cord injury caused by compression at T10. Results showed that in the injured spinal cord, the expression of the astrocyte marker glial fibrillary acidic protein and inflammatory factors interleukin 1β, interleukin-6, and tumor necrosis factor-α had decreased, whereas that of neuronal survival marker microtubule-associated protein 2 and synaptic plasticity markers postsynaptic densification protein 95 and synaptophysin protein had increased. Additionally, neural signaling of the descending corticospinal tract was markedly improved and rat locomotor function recovered significantly. These findings suggest that double-target neural circuit-magnetic stimulation improves rat motor function by attenuating astrocyte activation, thus providing a theoretical basis for application of double-target neural circuit-magnetic stimulation in the clinical treatment of spinal cord injury.

Availability and safety assessment of infrared neural stimulation at high repetition rate through an implantable optrode

An implantable optrode with micro-thermal detectors was designed to investigate the availability and safety of INS using high repetition rates.Optical auditory brainstem responses(oABRs)were recorded in normal-hearing guinea pigs,and the energy thresholds,pulse durations,and ampli-tudes evoked by the varied stimulus repetitions were analyzed.Stable oABRs could be evoked through INS even as the repetition rate of stimulation reached 19 kHz.The energy threshold of oABRs was elevated,the amplitudes decreased as pulse durations increased and repetition rates were higher,and the latencies were delayed as the pulse durations increased.The temperature variation curves on the site of stimulation significantly increased as the pulse duration increased to 400μs.INS elevated the temperature around the stimulus site area via thermal accumulation during radiation,especially when higher repetition stimuli were used.Our results demonstrate that high repetition infrared stimulations can safely evoke stable and available oABRs in normal-hearing guinea pigs.

Optimising repetitive transcranial magnetic stimulation for neural circuit repair following traumatic brain injury

While it is well-known that neuronal activity promotes plasticity and connectivity, the success of activity-based neural rehabilitation programs remains extremely limited in human clinical experience because they cannot adequately control neuronal excitability and activity within the injured brain in order to induce repair. However, it is possible to non-invasively modulate brain plasticity using brain stimu- lation techniques such as repetitive transcranial （rTMS） and transcranial direct current stimulation （tDCS） techniques, which show promise for repairing injured neural circuits （Henrich-Noack et al., 2013; Lefaucher et al., 2014）. Yet we are far from having full control of these techniques to repair the brain following neurotrauma and need more fundamen- tal research （Ellaway et al., 2014; Lefaucher et al., 2014）. In this perspective we discuss the mechanisms by which rTMS may facilitate neurorehabilitation and propose experimental techniques with which magnetic stimulation may be investi- gated in order to optimise its treatment potential.

Retinal ganglion cells regenerate long-distance axons through neural activity stimulation and find their way back to the brain

Human central nerve system(CNS)is an extremely complex and delicate structure.While regeneration is possible in some reptiles and fish CNS,the regeneration capacity seems completely lost in adult mammals.Therefore,the classic concept is that once neurons in mammal

Systems Neuroengineering: Understanding and Interacting with the Brain

In this paper, we review the current state- of-the-art techniques used for understanding the inner workings of the brain at a systems level. The neural activity that governs our everyday lives involves an intricate coordination of many processes that can be attributed to a variety of brain regions. On the surface, many of these functions can appear to be controlled by specific anatomical structures; however, in reality, numerous dynamic networks within the brain contribute to its function through an interconnected web of neuronal and synaptic pathways. The brain, in its healthy or pathological state, can therefore be best understood by taking a systems-level approach. While numerous neuroengineering technologies exist, we focus here on three major thrusts in the field of systems neuroengineering： neuroimaging, neural interfacing, and neuromodulation. Neuroimaging enables us to delineate the structural and functional organization of the brain, which is key in understanding how the neural system functions in both normal and disease states. Based on such knowledge, devices can be used either to communicate with the neural system, as in neural interface systems, or to modulate brain activity, as in neuromodulation systems. The consideration of these three fields is key to the development and application of neuro-devices. Feedback-based neuro-devices require the ability to sense neural activity （via a neuroimaging modality） through a neural interface （invasive or noninvasive） and ultimately to select a set of stimulation parameters in order to alter neural function via a neuromodulation modality. Systems neuroengineering refers to the use of engineering tools and technologies to image, decode, and modulate the brain in order to comprehend its functions and to repair its dysfunction. Interactions between these fields will help to shape the future of systems neuroengineering--to develop neurotechniques for enhancing the understanding of whole- brain function and dysfunction, and the management of neurological and mental disorders.

Lower urinary tract dysfunction in pediatrics progress to kidney disease in adolescents:Toward precision medicine in treatment

Newborn infants who had neurogenic bladder dysfunction(NBD)have a normal upper urinary tract at birth.Most of them will develop deterioration of renal function and chronic kidney disease if they do not receive proper management.Children with NBD can develop renal damage at adolescence or earlier,which is due to high detrusor pressures resulted from poor compliance of the bladder,detrusor overactivity against a closed sphincter or detrusor sphincter dyssynergia.To preserve renal function and prevent deterioration of the kidneys,NBD must be treated immediately after being diagnosed.Over the last few years there was great progress in the treatment of children with the NBD.We searched PubMed and the Cochrane Library for peer-reviewed articles published in any language up to March 10,2021,using the search term“neurogenic bladder children.”Our search excluded diagnosis,pathophysiology,surgical treatment of spinal cord injury and spina bifida.The research identified the effectiveness of treatment regimens targeting prevention of chronic kidney disease and the indications of kidney transplantation.The results of the research showed that NBD in children should be diagnosed early in life,and the child should receive the proper management.The literature search concluded that the management of NBD in children would be personalized for every case and could be changed according to response to treatment,side effects,child compliance,availability of treatment modality and costs of treatment.The objectives of the study are to present the different options of management of NBD in children and the selection of the proper method in a personalized manner.

Does a combined intervention program of repetitive transcranial magnetic stimulation and intensive occupational therapy affect cognitive function in patients with post-stroke upper limb hemiparesis?

Low-frequency repetitive transcranial magnetic stimulation（LF-r TMS） to the contralesional hemisphere and intensive occupational therapy（i OT） have been shown to contribute to a significant improvement in upper limb hemiparesis in patients with chronic stroke. However, the effect of the combined intervention program of LF-r TMS and i OT on cognitive function is unknown. We retrospectively investigated whether the combined treatment influence patient＇s Trail-Making Test part B（TMT-B） performance, which is a group of easy and inexpensive neuropsychological tests that evaluate several cognitive functions. Twenty-five patients received 11 sessions of LF-r TMS to the contralesional hemisphere and 2 sessions of i OT per day over 15 successive days. Patients with right- and left-sided hemiparesis demonstrated significant improvements in upper limb motor function following the combined intervention program. Only patients with right-sided hemiparesis exhibited improved TMT-B performance following the combined intervention program, and there was a significant negative correlation between Fugl-Meyer Assessment scale total score change and TMT-B performance. The results indicate the possibility that LF-r TMS to the contralesional hemisphere combined with i OT improves the upper limb motor function and cognitive function of patients with right-sided hemiparesis. However, further studies are necessary to elucidate the mechanism of improved cognitive function.

Electrical stimulation of dog pudendal nerve regulates the excitatory pudendal-to-bladder reflex

Pudendal nerve plays an important role in urine storage and voiding.Our hypothesis is that a neuroprosthetic device placed in the pudendal nerve trunk can modulate bladder function after suprasacral spinal cord injury.We had confirmed the inhibitory pudendal-to-bladder reflex by stimulating either the branch or the trunk of the pudendal nerve.This study explored the excitatory pudendal-to-bladder reflex in beagle dogs,with intact or injured spinal cord,by electrical stimulation of the pudendal nerve trunk.The optimal stimulation frequency was approximately 15–25 Hz.This excitatory effect was dependent to some extent on the bladder volume.We conclude that stimulation of the pudendal nerve trunk is a promising method to modulate bladder function.

Pulsed electrical stimulation protects neurons in the dorsal root and anterior horn of the spinal cord after peripheral nerve injury

Most studies on peripheral nerve injury have focused on repair at the site of injury, but very few have examined the effects of repair strategies on the more proximal neuronal cell bodies. In this study, an approximately 10-mm-long nerve segment from the ischial tuberosity in the rat was transected and its proximal and distal ends were inverted and sutured. The spinal cord was subjected to pulsed electrical stimulation at T10 and L3, at a current of 6.5 m A and a stimulation frequency of 15 Hz, 15 minutes per session, twice a day for 56 days. After pulsed electrical stimulation, the number of neurons in the dorsal root ganglion and anterior horn was increased in rats with sciatic nerve injury. The number of myelinated nerve fibers was increased in the sciatic nerve. The ultrastructure of neurons in the dorsal root ganglion and spinal cord was noticeably improved. Conduction velocity of the sciatic nerve was also increased. These results show that pulsed electrical stimulation protects sensory neurons in the dorsal root ganglia as well as motor neurons in the anterior horn of the spinal cord after peripheral nerve injury, and that it promotes the regeneration of peripheral nerve fibers.

Real-time and wearable functional electrical stimulation system for volitional hand motor function control using the electromyography bridge method

Voluntary participation of hemiplegic patients is crucial for functional electrical stimulation therapy.A wearable functional electrical stimulation system has been proposed for real-time volitional hand motor function control using the electromyography bridge method.Through a series of novel design concepts,including the integration of a detecting circuit and an analog-to-digital converter,a miniaturized functional electrical stimulation circuit technique,a low-power super-regeneration chip for wireless receiving,and two wearable armbands,a prototype system has been established with reduced size,power,and overall cost.Based on wrist joint torque reproduction and classification experiments performed on six healthy subjects,the optimized surface electromyography thresholds and trained logistic regression classifier parameters were statistically chosen to establish wrist and hand motion control with high accuracy.Test results showed that wrist flexion/extension,hand grasp,and finger extension could be reproduced with high accuracy and low latency.This system can build a bridge of information transmission between healthy limbs and paralyzed limbs,effectively improve voluntary participation of hemiplegic patients,and elevate efficiency of rehabilitation training.

Does hemispheric lateralization influence therapeutic effects of transcranial direct current stimulation?

This study investigated the effect of transcranial direct current stimulation（t DCS） polarity depending on lateralized function of task property in normal individuals performing visuomotor and simple repetitive tasks. Thirty healthy participants with no neurological disorders were recruited to participate in this study. Participants were randomly allocated into active or control condition. For the active condition, t DCS intensity was 2 m A with stimulation applied for 15 minutes to the right hemisphere（t DCS condition）. For the sham control, electrodes were placed in the same position, but the stimulator was turned off after 30 seconds（sham condition）. The tapping and tracking task tests were performed before and after for both conditions. Univariate analysis revealed significant difference only in the tracking task. For direct comparison of both tasks within each group, the tracking task had significantly higher Z score than the tapping task in the t DCS group（P 〈 0.05）. Thus, our study indicates that stimulation of the right hemisphere using t DCS can effectively improve visuomotor（tracking） task over simple repetitive（tapping） task.

Nano functional neural interfaces

Engineered functional neural interfaces （fNIs） serve as essential abiotic-biotic transducers between an engineered system and the nervous system. They convert external physical stimuli to cellular signals in stimulation mode or read out biological processes in recording mode. Information can be exchanged using electricity, light, magnetic fields, mechanical forces, heat, or chemical signals. fNIs have found applications for studying processes in neural circuits from cell cultures to organs to whole organisms, fNI-facilitated signal transduction schemes, coupled with easily manipulable and observable external physical signals, have attracted considerable attention in recent years. This enticing field is rapidly evolving toward miniaturization and biomimicry to achieve long-term interface stability with great signal transduction efficiency. Not only has a new generation of neuroelectrodes been invented, but the use of advanced fNIs that explore other physical modalities of neuromodulation and recording has begun to increase. This review covers these exciting developments and applications of fNIs that rely on nanoelectrodes, nanotransducers, or bionanotransducers to establish an interface with the nervous system. These nano fNIs are promising in offering a high spatial resolution, high target specificity, and high communication bandwidth by allowing for a high density and count of signal channels with minimum material volume and area to dramatically improve the chronic integration of the fNI to the target neural tissue. Such demanding advances in nano fNIs will greatly facilitate new opportunities not only for studying basic neuroscience but also for diagnosing and treating various neurological diseases.