Rehabilitation training combined acupuncture for limb hemiplegia caused by cerebral infarction: A protocol for a systematic review of randomized controlled trial.

BACKGROUND: Previous studies have reported that rehabilitation training combined acupuncture (RTA) can be used for the treatment of limb hemiplegia (LH) caused by cerebral infarction (CI). However, its effectiveness is still unclear. In this systematic review study, we aim to evaluate the effectiveness and safety of RTA for LH following CI. METHODS: We will retrieve the databases of CENTRAL, EMBASE, MEDILINE, CINAHL, AMED, CBM, PUBMED, and CNKI from inception to June 1, 2020 with no language restrictions. The randomized controlled trials of RTA for evaluating effectiveness and safety in patients with LH following CI will be included. Cochrane risk of bias tool will be used to measure the methodological quality for all included studies. Two authors will independently select the studies, extract the data, and assess the methodological quality of included studies. A third author will be invited to discuss if any disagreements exist between 2 authors. We will perform heterogeneity assessment before carrying out meta-analysis. According to the heterogeneity, we select random effect model or fixed effect model for meta-analysis of the included cohort studies. Cochrane risk of bias tool will be used to determine the methodological quality for included studies. RevMan 5.3 software (Cochrane Community, London, UK) will be utilized to perform statistical analysis. RESULTS: This systematic review will assess the effectiveness and safety of RTA for LH caused by CI. The primary outcome includes limbs function, as measured by the Wolf Motor Function Test (WMFT) Assessment scale, or other associated scales. The secondary outcomes consist of muscle strength, muscle tone, quality of life, and any adverse events. CONCLUSION: The findings of this study will summarize the current evidence of RTA for LH caused by CI, and may provide helpful evidence for the clinical treatment. DISSEMINATION AND ETHICS: The findings of this study are expected to be published in peer-reviewed journals. It does not require ethical approval, because no individual data will be utilized in this study. SYSTEMATIC REVIEW REGISTRATION: INPLASY202070114.

Interlimb conditioning of lumbosacral spinally evoked motor responses after spinal cord injury.

OBJECTIVE: The importance of subcortical pathways to functional motor recovery after spinal cord injury (SCI) has been demonstrated in multiple animal models. The current study evaluated descending interlimb influence on lumbosacral motor excitability after chronic SCI in humans. METHODS: Ulnar nerve stimulation and transcutaneous electrical spinal stimulation were used in a condition-test paradigm to evaluate the presence of interlimb connections linking the cervical and lumbosacral spinal segments in non-injured (n=15) and spinal cord injured (SCI) (n=18) participants. RESULTS: Potentiation of spinally evoked motor responses (sEMRs) by ulnar nerve conditioning was observed in 7/7 SCI participants with volitional leg muscle activation, and in 6/11 SCI participants with no volitional activation. Of these six, conditioning of sEMRs was present only when the neurological level of injury was rostral to the ulnar innervation entry zones. CONCLUSIONS: Descending modulation of lumbosacral motor pools via interlimb projections may exist in SCI participants despite the absence of volitional leg muscle activation. SIGNIFICANCE: Evaluation of sub-clinical, spared pathways within the spinal cord after SCI may provide an improved understanding of both the contributions of different pathways to residual function, and the mechanisms of plasticity and functional motor recovery following rehabilitation..

Cortical Brain-Computer Interface for Closed-Loop Deep Brain Stimulation.

Essential tremor is the most common neurological movement disorder. This progressive disease causes uncontrollable rhythmic motions-most often affecting the patient'sdominant upper extremity-thatoccur during volitional movement and make it difficult for the patient to perform everyday tasks. Medication may also become ineffective as the disorder progresses. For many patients, deep brain stimulation (DBS) of the thalamus is an effective means of treating this condition when medication fails. In current use, however, clinicians set the patient's stimulator to apply stimulation at all times-whether it is needed or not. This practice leads to excess power use, and more rapid depletion of batteries that require surgical replacement. In this paper, for the first time, neural sensing of movement (using chronically implanted cortical electrodes) is used to enable or disable stimulation for tremor. Therapeutic stimulation is delivered onlywhen the patient is actively using their effected limb, thereby reducing the total stimulation applied, and potentially extending the lifetime of surgically implanted batteries. This paper, which involves both implanted and external subsystems, paves the way for fully-implanted closed-loop DBS in the future.

The nondecussating pathway of the dentatorubrothalamic tract in humans: human connectome-based tractographic study and microdissection validation.

OBJECT The dentatorubrothalamic tract (DRTT) is the major efferent cerebellar pathway arising from the dentate nucleus (DN) and decussating to the contralateral red nucleus (RN) and thalamus. Surprisingly, hemispheric cerebellar output influences bilateral limb movements. In animals, uncrossed projections from the DN to the ipsilateral RN and thalamus may explain this phenomenon. The aim of this study was to clarify the anatomy of the dentatorubrothalamic connections in humans. METHODS The authors applied advanced deterministic fiber tractography to a template of 488 subjects from the Human Connectome Project (Q1-Q3 release, WU-Minn HCP consortium) and validated the results with microsurgical dissection of cadaveric brains prepared according to Klingler's method. RESULTS The authors identified the "classic" decussating DRTT and a corresponding nondecussating path (the nondecussating DRTT, nd-DRTT). Within each of these 2 tracts some fibers stop at the level of the RN, forming the dentatorubro tract and the nondecussating dentatorubro tract. The left nd-DRTT encompasses 21.7% of the tracts and 24.9% of the volume of the left superior cerebellar peduncle, and the right nd-DRTT encompasses 20.2% of the tracts and 28.4% of the volume of the right superior cerebellar peduncle. CONCLUSIONS The connections of the DN with the RN and thalamus are bilateral, not ipsilateral only. This affords a potential anatomical substrate for bilateral limb motor effects originating in a single cerebellar hemisphere under physiological conditions, and for bilateral limb motor impairment in hemispheric cerebellar lesions such as ischemic stroke and hemorrhage, and after resection of hemispheric tumors and arteriovenous malformations. Furthermore, when a lesion is located on the course of the dentatorubrothalamic system, a careful preoperative tractographic analysis of the relationship of the DRTT, nd-DRTT, and the lesion should be performed in order to tailor the surgical approach properly and spare all bundles.

Initiation and modulation of locomotor circuitry output with multisite transcutaneous electrical stimulation of the spinal cord in noninjured humans.

The mammalian lumbar spinal cord has the capability to generate locomotor activity in the absence of input from the brain. Previously, we reported that transcutaneous electrical stimulation of the spinal cord at vertebral level T11 can activate the locomotor circuitry in noninjured subjects when their legs are placed in a gravity-neutral position (Gorodnichev RM, Pivovarova EA, Pukhov A, Moiseev SA, Savokhin AA, Moshonkina TR, Shcherbakova NA, Kilimnik VA, Selionov VA, Kozlovskaia IB, Edgerton VR, Gerasimenko IU. Fiziol Cheloveka 38: 46-56, 2012). In the present study we hypothesized that stimulating multiple spinal sites and therefore unique combinations of networks converging on postural and locomotor lumbosacral networks would be more effective in inducing more robust locomotor behavior and more selective control than stimulation of more restricted networks. We demonstrate that simultaneous stimulation at the cervical, thoracic, and lumbar levels induced coordinated stepping movements with a greater range of motion at multiple joints in five of six noninjured subjects. We show that the addition of stimulation at L1 and/or at C5 to stimulation at T11 immediately resulted in enhancing the kinematics and interlimb coordination as well as the EMG patterns in proximal and distal leg muscles. Sequential cessation of stimulation at C5 and then at L1 resulted in a progressive degradation of the stepping pattern. The synergistic and interactive effects of transcutaneous stimulation suggest a multisegmental convergence of descending and ascending, and most likely propriospinal, influences on the spinal neuronal circuitries associated with locomotor activity. The potential impact of using multisite spinal cord stimulation as a strategy to neuromodulate the spinal circuitry has significant implications in furthering our understanding of the mechanisms controlling posture and locomotion and for regaining significant sensorimotor function even after a severe spinal cord injury.

Closed-loop neuromodulation of spinal sensorimotor circuits controls refined locomotion after complete spinal cord injury.

Neuromodulation of spinal sensorimotor circuits improves motor control in animal models and humans with spinal cord injury. With common neuromodulation devices, electrical stimulation parameters are tuned manually and remain constant during movement. We developed a mechanistic framework to optimize neuromodulation in real time to achieve high-fidelity control of leg kinematics during locomotion in rats. We first uncovered relationships between neuromodulation parameters and recruitment of distinct sensorimotor circuits, resulting in predictive adjustments of leg kinematics. Second, we established a technological platform with embedded control policies that integrated robust movement feedback and feed-forward control loops in real time. These developments allowed us to conceive a neuroprosthetic system that controlled a broad range of foot trajectories during continuous locomotion in paralyzed rats. Animals with complete spinal cord injury performed more than 1000 successive steps without failure, and were able to climb staircases of various heights and lengths with precision and fluidity. Beyond therapeutic potential, these findings provide a conceptual and technical framework to personalize neuromodulation treatments for other neurological disorders.

Antinociception induced by motor cortex stimulation: somatotopy of behavioral response and profile of neuronal activation.

Motor cortex stimulation (MCS) is used as a therapy for patients with refractory neuropathic pain. Experimental evidence suggests that the motor cortex (MC) is involved in the modulation of normal nociceptive response, but the underlying mechanisms have not been clarified yet. In previous studies, we demonstrated that MCS increases the nociceptive threshold of naive conscious rats by inhibiting thalamic sensory neurons and disinhibiting the neurons in periaqueductal gray (PAG), with the involvement of the opioid system. The aim of this study was to investigate the possible somatotopy of the motor cortex on MCS-induced antinociception and the pattern of neuronal activation evaluated by Fos and Egr-1 immunolabel in an attempt to better understand the relation between MC and analgesia. Rats received epidural electrode implants placed over the MC, in three distinct areas (forelimb, hindlimb or tail), according to a functional mapping established in previous studies. Nociceptive threshold was evaluated under 15-min electrical stimulating sessions. MCS induced selective antinociception in the limb related to the stimulated cortex, with no changes in other evaluated areas. MCS decreased Fos immunoreactivity (Fos-IR) in the superficial layers of the dorsal horn of the spinal cord for all evaluated groups and increased Fos-IR in the PAG, although no changes were observed in the PAG for the tail group. Egr-1 results were similar to those obtained for Fos. Data shown herein demonstrate that MCS elicits a substantial and selective antinociceptive effect, which is mediated, at least in part, by the activation of descendent inhibitory pain pathway.

Accelerated high-yield generation of limb-innervating motor neurons from human stem cells.

Human pluripotent stem cells are a promising source of differentiated cells for developmental studies, cell transplantation, disease modeling, and drug testing. However, their widespread use even for intensely studied cell types like spinal motor neurons is hindered by the long duration and low yields of existing protocols for in vitro differentiation and by the molecular heterogeneity of the populations generated. We report a combination of small molecules that within 3 weeks induce motor neurons at up to 50% abundance and with defined subtype identities of relevance to neurodegenerative disease. Despite their accelerated differentiation, motor neurons expressed combinations of HB9, ISL1, and column-specific markers that mirror those observed in vivo in human embryonic spinal cord. They also exhibited spontaneous and induced activity, and projected axons toward muscles when grafted into developing chick spinal cord. Strikingly, this novel protocol preferentially generates motor neurons expressing markers of limb-innervating lateral motor column motor neurons (FOXP1(+)/LHX3(-)). Access to high-yield cultures of human limb-innervating motor neuron subtypes will facilitate in-depth study of motor neuron subtype-specific properties, disease modeling, and development of large-scale cell-based screening assays.

Neonatal ventral hippocampal lesions modify pain perception and evoked potentials in rats.

This work concerns the debate surrounding the modified pain reactivity of patients with schizophrenia and other possible perceptive distortions. Rats with a neonatal ventral hippocampal lesion (NVHL) were used to model the neuro-developmental aspect of schizophrenia, and their reactivity to various stimuli was evaluated. The results could also help understand sensory deficits in other neuro-developmental disorders. Behavioural reactions to graduated painful thermal and mechanical stimuli were observed, and evoked potential responsiveness to tactile, visual and acoustic non-painful stimuli was recorded and compared to non-operated and sham lesioned controls. A higher threshold was observed with painful mechanical stimuli and shorter paw withdrawal latency with thermal stimuli. This was particularly relevant as there was no change in the evoked potentials triggered by non-nociceptive tactile stimulation of the same part of the body. There was a 10 dB(A) increase in the auditory threshold and a suppression of auditory sensory motor gating. Visually evoked potentials did not appear to be affected. Taken together, the results showed that NVHL-evoked alteration of brain development induces mechanical hypoalgesia, thermal hyperalgesia and auditory sensory changes. The data also contribute towards elucidating mechanisms underlying sensory deficits in neurodevelopmental diseases, including schizophrenia.

Imaginative resonance training (IRT) achieves elimination of amputees' phantom pain (PLP) coupled with a spontaneous in-depth proprioception of a restored limb as a marker for permanence and supported by pre-post functional magnetic resonance imaging (fMRI).

Non-pharmacological approaches such as mirror therapy and graded motor imagery often provide amelioration of amputees' phantom limb pain (PLP), but elimination has proved difficult to achieve. Proprioception of the amputated limb has been noted in studies to be defective and/or distorted in the presence of PLP, but has not, apparently, been researched for various stages of amelioration up to the absence of PLP. Previous studies using functional magnetic resonance imaging (fMRI) suggested that pathological cortical reorganisation after amputation may be the underlying neurobiological correlate of PLP. We report two cases of permanent elimination of PLP after application of imaginative resonance training. The patients, 69 years and 84 years old, reported freedom from PLP together with in-depth achievement of proprioception of a restored limb at the end of the treatment, which may thus be taken as an indication of permanence. Pre/post fMRI for the first case showed, against a group of healthy controls, analogous changes of activation in the sensorimotor cortex.

Motor function rebuilding of limbs based on communication principle and electronic system.

In this paper, we report our novel idea on the function rebuilding for hemiplegic limbs and the primary experiments. The main concept is to connect the control-lost nerves or neuromuscular junctions by using a multi-channel micro- electronic neural bridge (MENB), regenerate the nervous signal, and rebuild the motor functions of the related limb. Since the injured nervous system in stroke-related hemiplegia is located in the brain and difficult to be identified and operate on, we use another nervous system functioning as a new signal source to supply similar neural signals. In these cases, that means, two independent nervous systems are connected by a MENB. As preclinical experiments, we have made a series of tests on bodies of animals and healthy human. The principle, the system construction and the experimental results will be given.

Morphological and physiological regeneration in the auditory system of adult Mecopoda elongata (Orthoptera: Tettigoniidae).

Orthopterans are suitable model organisms for investigations of regeneration mechanisms in the auditory system. Regeneration has been described in the auditory systems of locusts (Caelifera) and of crickets (Ensifera). In this study, we comparatively investigate the neural regeneration in the auditory system in the bush cricket Mecopoda elongata. A crushing of the tympanal nerve in the foreleg of M. elongata results in a loss of auditory information transfer. Physiological recordings of the tympanal nerve suggest outgrowing fibers 5 days after crushing. An anatomical regeneration of the fibers within the central nervous system starts 10 days after crushing. The neuronal projection reaches the target area at day 20. Threshold values to low frequency airborne sound remain high after crushing, indicating a lower regeneration capability of this group of fibers. However, within the central target area the low frequency areas are also innervated. Recordings of auditory interneurons show that the regenerating fibers form new functional connections starting at day 20 after crushing.

Functional tracing of medial nociceptive pathways using activity-dependent manganese-enhanced MRI.

Manganese ion (Mn(2+)) was used as a paramagnetic contrast agent in T1-weighted magnetic resonance imaging (MRI) images. They enter neural cells though voltage-gated calcium channels and are activity-dependently transported along axons and across synapses. The aim of the present study was to investigate the nociceptive medial thalamus projection in rats by activity-dependent manganese-enhanced magnetic resonance imaging (MEMRI). Rats under urethane and α-chloralose anesthesia were microinjected with manganese chloride (MnCl(2), 120mmol/L, iontophoretically with a 5-µA current for 15min) into the right medial thalamus. Innocuous (at a 50-µA intensity for 0.2ms) or noxious (at a 5-mA intensity for 2ms) electrical stimuli were applied through a pair of needles in the left forepaw pads once every 6s for 5h. Enhanced transport of Mn(2+) were found in the anterior cingulate cortex, midcingulate cortex, retrosplenial cortex, ventral medial caudate-putamen, nucleus accumbens, and amygdala in the noxious-stimulated group. Enhancements in the anterior cingulate cortex, midcingulate cortex, ventral medial caudate-putamen, nucleus accumbens, and amygdala, but not the retrosplenial cortex, were attenuated by an intraperitoneal injection of morphine (5mg/kg and 1mg/kg/h, intraperitoneal). These results indicate that a combination of MEMRI with activity-induced manganese-dependent contrast is useful for delineating functional connections in the pain pathway. Noxious stimulation induced enhancement of manganese ion transportation from medial thalamus to cingulate cortex and medial striatum, but not motor cortex. A combination of manganese-enhanced magnetic resonance imaging with activity-dependent contrast is useful for delineating functional connections of the medial pain pathway.

Myogenesis in the thoracic limbs of the American lobster.

Newly hatched lobster larvae have biramous thoracic limbs composed of an endopodite, which is used for walking in the adult, and an exopodite used for swimming. Several behavioural and physiological aspects of larval locomotion as well the ontogeny of the neuromuscular system have been examined in developing decapod crustaceans. Nevertheless, the cellular basis of embryonic muscle formation in these animals is poorly understood. Therefore, the present report analyses muscle formation in embryos of the American lobster Homarus americanus Milne Edwards, 1837 (Malacostraca, Eucarida, Decapoda, Homarida) using the monoclonal antibody 016C6 that recognizes an isoform of myosin heavy chain. 016C6 labelling at 25% of embryonic development (E25%) revealed that syncytial muscle precursor cells establish the muscles in the endopodites. During subsequent embryogenesis, these muscle precursors subdivide into several distinct units thereby giving rise to pairs of antagonistic primordial muscles in each of the successive podomeres, the layout of which at E45% already resembles the arrangement in the adult thoracopods. The pattern of primordial muscles was also mapped in the exopodites of thoracic limbs three to eight. Immunohistochemistry against acetylated α-tubulin and against presynaptic vesicle-associated phosphoproteins at E45% demonstrated the existence of characteristic neural tracts within the developing limbs as well as putative neuromuscular synapses in both the embryonic exo- and endopodites. The results are compared to muscle development in other Crustacea.

Ultrasound-guided permanent implantation of peripheral nerve stimulation (PNS) system for neuropathic pain of the extremities: original cases and outcomes.

OBJECTIVE: Our objective is to describe our experience applying a minimally invasive, ultrasound-assisted technique for peripheral nerve stimulation (PNS) trial and permanent implantation in patients with neuropathic extremity pain. DESIGN: Retrospective case series and review of the literature. Setting. Tertiary referral center and academic medical center. PATIENTS: Patients with upper or lower extremity neuropathic pain resistant to other therapies who responded to an ultrasound-guided peripheral nerve block at a proximal location. Interventions. Ultrasound-assisted through-the-needle placement of percutaneous neurostimulation electrodes on target major peripheral nerves for fully percutaneous trial, staged trial or permanent implantation of PNS system. A PNS trial period of 3-7 days was used. OUTCOME MEASURES: Pain relief at last follow-up, complications, therapeutic limitations due to technique as applied. Results. Six of eight (75%) patients and 7/9 (78%) peripheral nerves had a successful trial and underwent permanent PNS system implantation using a minimally invasive, ultrasound-assisted technique from November 2007 to December 2008. All but one patient with an implanted PNS system had > or =50% pain relief at last follow-up and 3/7 (43%) permanent systems were associated with > or =80% relief. Loss of paresthesia required revision to dual-lead systems in upper extremity radial nerve PNS. Infection led to explant in one case. CONCLUSIONS: In a small series of patients, a minimally invasive, ultrasound-assisted technique for PNS trial, and permanent PNS implantation proved feasible. Patients without adequate analgesia during neurostimulation trial avoided surgical incision and those undergoing permanent implantation were not subjected to the potential morbidity associated with nerve dissection.

Complete optical neurophysiology: toward optical stimulation and recording of neural tissue.

Direct optical methods to stimulate and record neural activity provide artifact-free, noninvasive, and noncontact neurophysiological procedures. For stimulation, focused mid-infrared light alters membrane potential and activates individual neural processes. Simultaneous intrinsic scattered light parameters, including birefringence changes, can record neural activity with signals similar to potentiometric dyes. The simultaneous combination of optical stimulation and optical recording techniques provide the potential for powerful tools that may someday remove the need for invasive wires during electrophysiological recordings.

Decreased brain activation to tongue movements in amyotrophic lateral sclerosis with bulbar involvement but not Kennedy syndrome.

Neuroimaging studies in amyotrophic lateral sclerosis (ALS) investigating movements of the hands have in general found increased activation compared to healthy controls, which has been interpreted in terms of cortical adaptation as a result of corticospinal tract damage. Here, we investigated brain activations to vertical tongue movements using functional MRI at 3 tesla. Whereas healthy controls, patients with Kennedy syndrome, and ALS patients without bulbar involvement showed robust and indistinguishable activations in pre- and postcentral areas and the thalamus, ALS patients with bulbar involvement showed a significant decrease of cortical activity and missing thalamic activity. This decrease stands in marked contrast to the increase of activity observed in ALS patients when performing limb movements. We discuss these divergent findings with regard to the different physiological properties of tongue and limb movements. These findings may also help to explain the faster time-course of the disease in patients with bulbar involvement.

Effects of practice, visual loss, limb amputation, and disuse on motor imagery vividness.

BACKGROUND: The ability to generate vivid images of movements is variable across individuals and likely influenced by sensorimotor inputs. OBJECTIVES: The authors examined (1) the vividness of motor imagery in dancers and in persons with late blindness, with amputation or an immobilization of one lower limb; (2) the effects of prosthesis use on motor imagery; and (3) the temporal characteristics of motor imagery. METHODS: Eleven dancers, 10 persons with late blindness, 14 with amputation, 6 with immobilization, and 2 groups of age-matched healthy individuals (27 in control group A; 35 in control group B) participated. The Kinesthetic and Visual Imagery Questionnaire served to assess motor imagery vividness. Temporal characteristics were assessed with mental chronometry. RESULTS: The late blindness group and dance group displayed higher imagery scores than respective control groups. In the amputation and immobilization groups, imagery scores were lower on the affected side than the intact side and specifically for imagined foot movements. Imagery scores of the affected limb positively correlated with the time since walking with prosthesis. Movement times during imagination and execution (amputation and immobilization) were longer on the affected side than the intact side, but the temporal congruence between real and imagined movement times was similar to that in the control group. CONCLUSIONS: The mental representation of actions is highly modulated by imagery practice and motor activities. The ability to generate vivid images of movements can be specifically weakened by limb loss or disuse, but lack of movement does not affect the temporal characteristics of motor imagery.

Short-form Tai Chi improves standing balance of people with chronic stroke.

BACKGROUND AND OBJECTIVE: Our previous findings showed that 4 weeks of intensive Tai Chi practice improved standing balance in healthy seniors. This study set out to investigate whether Tai Chi could improve standing balance in subjects with chronic stroke. METHODS: One hundred thirty-six subjects >6 months after stroke were randomly assigned to a control group (n = 62) practicing general exercises or a Tai Chi group (n = 74) for 12 weeks of training. Each week, 1 hour of group practice was supplemented by 3 hours of self-practice. We used a short-form of Tai Chi consisting of 12 forms that require whole-body movements to be performed in a continuous sequence and demands concentration. A blinded assessor examined subjects at baseline, 6 weeks (mid-program), 12 weeks (end-program), and 18 weeks (follow-up). The 3 outcome measures were (1) dynamic standing balance evaluated by the center of gravity (COG) excursion during self-initiated body leaning in 4 directions, (2) standing equilibrium evaluated in sensory challenged conditions, and (3) functional mobility assessed by Timed-up-and-go score. Mixed model repeated-measures analysis of variance was used to examine between-group differences. RESULTS: When compared with the controls, the Tai Chi group showed greater COG excursion amplitude in leaning forward, backward, and toward the affected and nonaffected sides (P < .05), as well as faster reaction time in moving the COG toward the nonaffected side (P = .014) in the end-program and follow-up assessments. The Tai Chi group also demonstrated better reliance on vestibular integration for balance control at end-program (P = .038). However, neither group improved significantly in Timed-up-and-go scores. CONCLUSIONS: Twelve weeks of short-form Tai Chi produced specific standing balance improvements in people with chronic stroke that outlasted training for 6 weeks.