Virtual reality interface devices in the reorganization of neural networks in the brain of patients with neurological diseases

Two key characteristics of all virtual reality applications are interaction and immersion. Systemic interaction is achieved through a variety of multisensory channels （hearing, sight, touch, and smell）, permitting the user to interact with the virtual world in real time. Immersion is the degree to which a person can feel wrapped in the virtual world through a defined interface. Virtual real- ity interface devices such as the Nintendo~ Wii and its peripheral nunchuks-balance board, head mounted displays and joystick allow interaction and immersion in unreal environments created from computer software. Virtual environments are highly interactive, generating great activation of visual, vestibular and proprioceptive systems during the execution of a video game. In addi- tion, they are entertaining and safe for the user. Recently, incorporating therapeutic purposes in virtual reality interface devices has allowed them to be used for the rehabilitation of neurological patients, e.g., balance training in older adults and dynamic stability in healthy participants. The improvements observed in neurological diseases （chronic stroke and cerebral palsy） have been shown by changes in the reorganization of neural networks in patients＇ brain, along with better hand function and other skills, contributing to their quality of life. The data generated by such studies could substantially contribute to physical rehabilitation strategies.     

Recombinant human erythropoietin increases cerebral cortical width index and neurogenesis following ischemic stroke

The cerebral cortical expansion index refers to the ratio between left and right cortex width and is recognized as an indicator for cortical hyperplasia. Cerebral ischemia was established in CB-17 mice in the present study, and the mice were subsequently treated with recombinant human erythropoietin via subcutaneous injection. Results demonstrated that cerebral cortical width index significantly increased. Immunofluorescence detection showed that the number of nuclear antigen antibody/5-bromodeoxyuridine-positive cells at the infarction edge significantly increased. Correlation analysis revealed a negative correlation between neurological scores and cortical width indices in rats following ischemic stroke. These experimental findings suggested that recombinant human erythropoietin promoted cerebral cortical hyperplasia, increased cortical neurogenesis, and enhanced functional recovery following ischemic stroke.     

Diffuse axonal injury after traumatic cerebral microbleeds： an evaluation of imaging techniques

Previous neuropathological studies regarding traumatic brain injury have primarily focused on changes in large structures, for example, the clinical prognosis after cerebral contusion, intrace- rebral hematoma, and epidural and subdural hematoma. In fact, many smaller injuries can also lead to severe neurological disorders. For example, cerebral microbleeds result in the dysfunc- tion of adjacent neurons and the disassociation between cortex and subcortical structures. These tiny changes cannot be adequately visualized on CT or conventional MRI. In contrast, gradient echo sequence-based susceptibility-weighted imaging is very sensitive to blood metabolites and microbleeds, and can be used to evaluate traumatic cerebral microbleeds with high sensitivity and accuracy. Cerebral microbleed can be considered as an important imaging marker for dif- fuse axonal injury with potential relevance for prognosis. For this reason, based on experimental and clinical studies, this study reviews the role of imaging data showing traumatic cerebral microbleeds in the evaluation of cerebral neuronal injury and neurofunctional loss.     

Effects of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper limb motor dysfunction in patients with subacute cerebral infarction

Studieshave confirmed that low-frequency repetitive transcranial magnetic stimulation can decrease the activity of cortical neurons, and high-frequency repetitive transcranial magnetic stimulation can increase the excitability of cortical neurons. However, there are few studies concerning the use of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper-limb motor function atfer cerebral infarction. We hypothesized that different frequencies of repetitive transcranial magnetic stimulation in patients with cerebral infarction would produce different effects on the recovery of upper-limb motor function. hTis study enrolled 127 patients with upper-limb dysfunction during the subacute phase of cerebral infarction. hTese patients were randomly assigned to three groups. hTe low-frequency group comprised 42 patients who were treated with 1 Hz repetitive transcranial magnetic stimulation on the contralateral hemisphere primary motor cortex (M1). hTe high-frequency group comprised 43 patients who were treated with 10 Hz repetitive transcranial magnetic stimulation on ipsilateral M1. Finally, the sham group comprised 42 patients who were treated with 10 Hz of false stimulation on ipsilateral M1. A total of 135 seconds of stimulation was applied in the sham group and high-frequency group. At 2 weeks atfer treatment, cortical latency of motor-evoked potentials and central motor conduction time were signiifcantly lower compared with before treatment. Moreover, motor function scores were signiifcantly improved. hTe above indices for the low- and high-frequency groups were signiifcantly different compared with the sham group. However, there was no signiifcant difference between the low- and high-frequency groups. hTe results show that low- and high-frequency repetitive transcranial magnetic stimulation can similarly improve upper-limb motor function in patients with cerebral infarction.     

Remodeling of motor cortex function in acute cerebral infarction patients following human urinary kallidinogenase A functional magnetic resonance imaging evaluation after 6 months

A total of 29 patients were treated within 48 hours after acute subcortical cerebral infarction with Xuesaitong or Xuesaitong plus human urinary kallidinogenase for 14 days.Neurological deficits,activity of daily living,and evaluations of distal upper limb motor functions at the 6-month follow-up showed that patients treated with Xuesaitong plus human urinary kallidinogenase recovered better than with Xuesaitong alone.In addition,functional MRI revealed that activation sites were primarily at the ipsilesional side of injury in all patients.Human urinary kallidinogenase induced hyperactivation of the ipsilesional primary sensorimotor cortex,premotor cortex,supplementary motor area,and contralesional posterior parietal cortex.Results showed that human urinary kallidinogenase improved symptoms of neurological deficiency by enhancing remodeling of long-term cortical motor function in patients with acute cerebral infarction.     

Regional Metabolic Changes Influencing Three-Dimensional Perception in Parkinson’s Disease

Background and PurposeStereopsis refers to the perception of depth and awareness of the distance of an object from the observer that results from the brain receiving visual stimuli from both eyes in combination. Patients with idiopathic Parkinson’s disease (PD patients) typically experience problems with vision, eyeball movements, and visual perception due to degeneration of the cells that generate dopamine in the brain. We therefore hypothesized that stereopsis is affected more by visual cortical dysfunction in idiopathic PD than by retina and subcortical structural dysfunction.MethodsWe analyzed stereopsis in 12 PD patients and 7 healthy controls using a three-dimensional (3D) television (TV). Before allowing patients to watch TV, we examined their visual acuity and strabismus using the Titmus Stereo Fly Test, and evaluated their cognitive function using cognitive tests. The patients watched 3D and two-dimensional (2D) versions of a movie with an approximate duration of 17 minutes, and then completed a questionnaire about stereopsis. All subjects underwent brain F-18 fluorodeoxyglucose (FDG) positron-emission tomography after watching the 3D version of the movie. One week later, subjects watched the 2D version of the same movie under the same conditions. Each scan was analyzed using statistical parametric mapping (version 8) software.ResultsThe visual cortex was activated less in the PD patients than in the healthy controls when watching the 2D or 3D movie. However, there was no significant difference between watching 2D and 3D movies in the PD patients or healthy controls.ConclusionsThe lower activation of the primary visual cortex in PD patients suggests the presence of dysfunction of the visual cortex. In addition, there was less activation of the visual association cortex in PD patients when watching a 3D movie than in controls under the same conditions. This might be one reason why PD patients do not recognize real and dynamic stereopsis. These findings have clinical significance since they suggest that safety needs to be considered when making devices or programs using 3D or virtual reality for use by patients with various cerebral degenerative diseases.     

Electroacupuncture stimulation of the brachial plexus trunk on the healthy side promotes brain-derived neurotrophic factor mRNA expression in the ischemic cerebral cortex of a rat model of cerebral ischemia/reperfusion injury

A rat model of cerebral ischemia/reperfusion was established by suture occlusion of the left middle cerebral artery. In situ hybridization results showed that the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic rat cerebral cortex increased after cerebral ischemia/ reperfusion injury. Low frequency continuous wave electroacupuncture (frequency 2-6 Hz, current intensity 2 mA) stimulation of the brachial plexus trunk on the healthy (right) side increased the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic cerebral cortex 14 days after cerebral ischemia/reperfusion injury. At the same time, electroacupuncture stimulation of the healthy brachial plexus truck significantly decreased neurological function scores and alleviated neurological function deficits. These findings suggest that electroacupuncture stimulation of the brachial plexus trunk on the healthy (right) side can greatly increase brain-derived neurotrophic factor mRNA expression and improve neurological function.     

Breviscapine reduces neuronal injury caused by traumatic brain injury insult:partly associated with suppression of interleukin-6 expression

Breviscapine,extracted from the herb Erigeron breviscapus,is widely used for the treatment of cardiovascular diseases,cerebral infarct,and stroke,but its mechanism of action remains unclear.This study established a rat model of traumatic brain injury induced by controlled cortical impact,and injected 75 μg breviscapine via the right lateral ventricle.We found that breviscapine significantly improved neurobehavioral dysfunction at 6 and 9 days after injection.Meanwhile,interleukin-6 expression was markedly down-regulated following breviscapine treatment.Our results suggest that breviscapine is effective in promoting neurological behavior after traumatic brain injury and the underlying molecular mechanism may be associated with the suppression of interleukin-6.     

Changes in brain activation in stroke patients after mental practice and physical exercise： a functional MRI study

Mental practice is a new rehabilitation method that reters to the mental rehearsal ot motor imagery content with the goal of improving motor performance. However, the relationship between activated regions and motor recovery after mental practice training is not well understood. In this study, 15 patients who suffered a firstever subcortical stroke with neurological deficits affecting the right hand, but no significant cognitive impairment were recruited. 10 patients underwent mental practice combined with physical practice training, and 5 patients only underwent physical practice training. We observed brain activation regions after 4 weeks of training, and explored the correlation of activation changes with functional recovery of the affected hands. The results showed that, after 4 weeks of mental practice combined with physical training, the Fugl-Meyer assessment score for the affected right hand was significantly increased than that after 4 weeks of practice training alone. Functional MRI showed enhanced activation in the left primary somatosensory cortex, attenuated activation intensity in the right primary motor cortex, and enhanced right cerebellar activation observed during the motor imagery task using the affected right hand after mental practice training. The changes in brain cortical activity were related to functional recovery of the hand. Experimental findings indicate that cortical and cerebellar functional reorganization following mental practice contributed to the improvement of hand function.     

Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury

To investigate the supplement of lost nerve cells in rats with traumatic brain injury by intravenous administration of allogenic bone marrow mesenchymal stem cells, this study established a Wistar rat model of traumatic brain injury by weight drop impact acceleration method and administered 3 × 106 rat bone marrow mesenchymal stem cells via the lateral tail vein. At 14 days after cell transplantation, bone marrow mesenchymal stem cells differentiated into neurons and astrocytes in injured rat cerebral cortex and rat neurological function was improved significantly. These findings suggest that intravenously administered bone marrow mesenchymal stem cells can promote nerve cell regeneration in injured cerebral cortex, which supplement the lost nerve cells.     

Large-conductance Ca2+-activated K+ channel involvement in suppression of cerebral ischemia/reperfusion injury after electroacupuncture atShuigou (GV26) acupoint in rats

Excess activation and expression of large-conductance Ca2+-activated K+ channels (BKCa channels) may be an important mechanism for delayed neuronal death after cerebral ischemia/reperfusion injury. Electroacupuncture can regulate BKCa channels after cerebral ischemia/reperfusion injury, but the precise mechanism remains unclear. In this study, we established a rat model of cerebral ischemia/reperfusion injury. Model rats received electroacupuncture of 1 mA and 2 Hz atShuigou (GV26) for 10 minutes, once every 12 hours for a total of six times in 72 hours. We found that in cerebral ischemia/reperfusion injury rats, ischemic changes in the cerebral cortex were mitigated after electroacupuncture. Moreover, BKCa channel protein and mRNA expression were reduced in the cerebral cortex and neurological function noticeably improved. These changes did not occur after electroacupuncture at a non-acupoint (5 mm lateral to the left side of Shuigou). Thus, our ifndings indicate that electroacupuncture atShuigou improves neurological function in rats following cerebral ischemia/reperfu-sion injury, and may be associated with down-regulation of BKCa channel protein and mRNA expression. Additionally, our results suggest that theShuigou acupoint has functional speciifcity.     

Compensatory recombination phenomena of neurological functions in central dysphagia patients

We speculate that cortical reactions evoked by swallowing activity may be abnormal in patients with central infarction with dysphagia. The present study aimed to detect functional imaging features of cerebral cortex in central dysphagia patients by using blood oxygen level-dependent functional magnetic resonance imaging techniques. The results showed that when normal controls swallowed, primary motor cortex(BA4), insula(BA13), premotor cortex(BA6/8), supramarginal gyrus(BA40), and anterior cingulate cortex(BA24/32) were activated, and that the size of the activated areas were larger in the left hemisphere compared with the right. In recurrent cerebral infarction patients with central dysphagia, BA4, BA13, BA40 and BA6/8 areas were activated, while the degree of activation in BA24/32 was decreased. Additionally, more areas were activated, including posterior cingulate cortex(BA23/31), visual association cortex(BA18/19), primary auditory cortex(BA41) and parahippocampal cortex(BA36). Somatosensory association cortex(BA7) and left cerebellum in patients with recurrent cerebral infarction with central dysphagia were also activated. Experimental findings suggest that the cerebral cortex has obvious hemisphere lateralization in response to swallowing, and patients with recurrent cerebral infarction with central dysphagia show compensatory recombination phenomena of neurological functions. In rehabilitative treatment, using the favorite food of patients can stimulate swallowing through visual, auditory, and other nerve conduction pathways, thus promoting compensatory recombination of the central cortex functions.     

Brain glucose metabolism in postanoxic syndrome. Positron emission tomographic study

Thirteen positron emission tomographic studies of cerebral glucose utilization were carried out in 12 patients with postanoxic syndrome due to cardiac arrest. Seven subjects were in a persistent vegetative state. The 5 other subjects were normally conscious, but disclosed focal neurological signs. When compared with normal values, mean cerebral glucose metabolism was drastically decreased (+/- 50%) in vegetative subjects, and to a lesser degree (+/- 25%) in conscious patients. The most consistent regional alterations were found in the parieto-occipital cortex (9 cases), the frontier between vertebral and carotid arterial territories, followed by the frontomesial junction (5 cases), the striatum (3 cases with dystonia), thalamus (2 cases), and visual cortex (2 cases with cortical blindness). These data suggest that brain anoxia can result in global brain hypometabolism, which appears related to the vigilance state, as well as in regional alterations preferentially located in arterial border zones.     

Neuronal injury in the motor cortex after chronic stroke and lower limb motor impairment: a voxelbased lesion symptom mapping study

Many studies have examined motor impairments using voxel-based lesion symptom mapping, but few are reported regarding the corresponding relationship between cerebral cortex injury and lower limb motor impairment analyzed using this technique. This study correlated neuro- nal injury in the cerebral cortex of 16 patients with chronic stroke based on a voxel-based lesion symptom mapping analysis. Neuronal injury in the corona radiata, caudate nucleus and putamen of patients with chronic stroke could predict walking speed. The behavioral measure scores were consistent with motor deficits expected after damage to the cortical motor system due to stroke. These findings suggest that voxel-based lesion symptom mapping may provide a more accurate prognosis of motor recovery from chronic stroke according to neuronal injury in cerebral motor cortex.     

Virtual Reality Neurorehabilitation

The present work investigates the application of virtual reality (VR) technology to neurorehabilitation. By consulting a wealth of data, the advantages of VR in neurorehabilitation are introduced, followed by the application status of VR in the rehabilitation of stroke patients, Parkinson’s patients, mental and psychological diseases. Besides, many research experiments on the application of VR technology in rehabilitation medicine at the present stage are investigated. The results indicate that compared with traditional balance training, the VR-based neurological rehabilitation training method can more effectively ease the tilt degree and strengthen the trunk control ability and balance function of patients with post-stroke tilt syndrome. When the effect of traditional rehabilitation training on the gait and balance of Parkinson’s patients is not good enough, VR-based rehabilitation training can at least be used as an alternative therapy. Moreover, VR games have made great breakthroughs in promoting limb rehabilitation and brain injury rehabilitation, which is of incredible benefit to those with motor and activity disorders. It is also beneficial to the treatment and recovery of mental disorders of patients with nerve injury. Although VR still has limitations such as high cost and technical breakthrough bottleneck, it has great advantages in relieving pain, enhancing interest, and recovering patients’ mental health in neurological rehabilitation training.     

Constraint-induced movement therapy promotes brain functional reorganization in stroke patients with hemiplegia

Stroke patients with hemiplegia exhibit flexor spasms in the upper limb and extensor spasms in the lower limb, and their movement patterns vary greatly. Constraint-induced movement therapy is an upper limb rehabilitation technique used in stroke patients with hemiplegia; however, studies of lower extremity rehabilitation are scarce. In this study, stroke patients with lower limb hemiplegia underwent conventional Bobath therapy for 4 weeks as baseline treatment, followed by constraint-induced movement therapy for an additional 4 weeks. The 10-m maximum walking speed and Berg balance scale scores significantly improved following treatment, and lower extremity motor function also improved. The results of functional MRI showed that constraint-induced movement therapy alleviates the reduction in cerebral functional activation in patients, which indicates activation of functional brain regions and a significant increase in cerebral blood perfusion. These results demonstrate that constraint-induced movement therapy promotes brain functional reorganization in stroke patients with lower limb hemiplegia.     

Electroacupuncture induces acute changes in cerebral cortical miRNA profile,improves cerebral blood flow and alleviates neurological deficits in a rat model of stroke

Electroacupuncture has been shown to improve cerebral blood flow in animal models of stroke. However, it is unclear whether electroacupuncture alters mi RNA expression in the cortex. In this study, we examined changes in the cerebral cortical mi RNA profile, cerebral blood flow and neurological function induced by electroacupuncture in a rat model of stroke. Electroacupuncture was performed at Renzhong(GV26) and Neiguan(PC6), with a frequency of 2 Hz, continuous wave, current intensity of 3.0 m A, and stimulation time of 1 minute. Electroacupuncture increased cerebral blood flow and alleviated neurological impairment in the rats. mi RNA microarray profiling revealed that the vascular endothelial growth factor signaling pathway, which links cell proliferation with stroke, was most significantly affected by electroacupuncture. Electroacupuncture induced changes in expression of rno-mi R-206-3p, rno-mi R-3473, rno-mi R-6216 and rno-mi R-494-3p, and these changes were confirmed by quantitative real-time polymerase chain reaction. Our findings suggest that changes in cell proliferation-associated mi RNA expression induced by electroacupuncture might be associated with the improved cerebral blood supply and functional recovery following stroke.     

Neural differentiation of human Wharton's jelly-derived mesenchymal stem cells improves the recovery of neurological function after transplantation in ischemic stroke rats

Human Wharton’s jelly-derived mesenchymal stem cells(h WJ-MSCs)have excellent proliferative ability,differentiation ability,low immunogenicity,and can be easily obtained.However,there are few studies on their application in the treatment of ischemic stroke,therefore their therapeutic effect requires further verification.In this study,h WJ-MSCs were transplanted into an ischemic stroke rat model via the tail vein 48 hours after transient middle cerebral artery occlusion.After 4 weeks,neurological functions of the rats implanted with h WJ-MSCs were significantly recovered.Furthermore,many h WJ-MSCs homed to the ischemic frontal cortex whereby they differentiated into neuron-like cells at this region.These results confirm that h WJ-MSCs transplanted into the ischemic stroke rat can differentiate into neuron-like cells to improve rat neurological function and behavior.     

Leap Motion-based virtual reality training for improving motor functional recovery of upper limbs and neural reorganization in subacute stroke patients

Virtual reality is nowadays used to facilitate motor recovery in stroke patients. Most virtual reality studies have involved chronic stroke patients; however, brain plasticity remains good in acute and subacute patients. Most virtual reality systems are only applicable to the proximal upper limbs(arms) because of the limitations of their capture systems. Nevertheless, the functional recovery of an affected hand is most difficult in the case of hemiparesis rehabilitation after a stroke. The recently developed Leap Motion controller can track the fine movements of both hands and fingers. Therefore, the present study explored the effects of a Leap Motion-based virtual reality system on subacute stroke. Twenty-six subacute stroke patients were assigned to an experimental group that received virtual reality training along with conventional occupational rehabilitation, and a control group that only received conventional rehabilitation. The Wolf motor function test(WMFT) was used to assess the motor function of the affected upper limb; functional magnetic resonance imaging was used to measure the cortical activation. After four weeks of treatment, the motor functions of the affected upper limbs were significantly improved in all the patients, with the improvement in the experimental group being significantly better than in the control group. The action performance time in the WMFT significantly decreased in the experimental group. Furthermore, the activation intensity and the laterality index of the contralateral primary sensorimotor cortex increased in both the experimental and control groups. These results confirmed that Leap Motion-based virtual reality training was a promising and feasible supplementary rehabilitation intervention, could facilitate the recovery of motor functions in subacute stroke patients. The study has been registered in the Chinese Clinical Trial Registry(registration number: Chi CTR-OCH-12002238).     

Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions

Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that causes motor, sensory, and cognitive deficits. The present study characterized demyelinated lesions in the cerebral cortex of MS patients. One hundred twelve cortical lesions were identified in 110 tissue blocks from 50 MS patients. Three patterns of cortical demyelination were identified: Type I lesions were contiguous with subcortical white matter lesions; Type II lesions were small, confined to the cortex, and often perivascular; Type III lesions extended from the pial surface to cortical layer 3 or 4. Inflammation and neuronal pathology were studied in tissue from 8 and 7 patients, respectively. Compared to white matter lesions, cortical lesions contained 13 times fewer CD3-positive lymphocytes (195 vs 2,596/mm3 of tissue) and 6 times fewer CD68-positive microglia/macrophages (11,948 vs 67,956/mm3 of tissue). Transected neurites (both axons and dendrites) occurred at a density of 4,119/mm3 in active cortical lesions, 1,107/mm3 in chronic active cortical lesions, 25/mm3 in chronic inactive cortical lesions, 8/mm3 in myelinated MS cortex, and 1/mm3 in control cortex. In active and chronic active cortical lesions, activated microglia closely apposed and ensheathed apical dendrites, neurites, and neuronal perikarya. In addition, apoptotic neurons were increased significantly in demyelinated cortex compared to myelinated cortex. These data support the hypothesis that demyelination, axonal transection, dendritic transection, and apoptotic loss of neurons in the cerebral cortex contribute to neurological dysfunction in MS patients.