A mosquito proboscis-inspired cambered microneedle patch for ophthalmic regional anaesthesia.

INTRODUCTION: One of the methods for pain management involves the use of local anesthesia, which numbs sensations in specific body regions while maintaining consciousness. OBJECTIVES: Considering the certain limitations (e.g., pain, the requirement of skilled professionals, or slow passive diffusion) of conventional delivery methods of local anesthetics, developing alternative strategies that offer minimally invasive yet therapeutically effective delivery systems is of great concern for ophthalmic regional anesthesia. METHODS AND RESULTS: In this study, a rapidly dissolving cambered microneedle (MNs) patch, composed of poly(vinylpyrrolidone) (PVP) and hyaluronic acid (HA) and served as a delivery system for lidocaine (Lido) in local anesthesia, was developed taking inspiration from the mosquito proboscis's ability to extract blood unnoticed. The lidocaine-containing MNs patch (MNs@Lido) consisted of 25 microneedles with a four-pronged cone structure (height: 500 µm, base width: 275 µm), arranged in a concentric circle pattern on the patch, and displays excellent dissolubility for effective drug delivery of Lido. After confirming good cytocompatibility, MNs@Lido was found to possess adequate rigidity to penetrate the cornea without causing any subsequent injury, and the created corneal pinhole channels completely self-healed within 24 h. Interestingly, MNs@Lido exhibited effective analgesic effects for local anesthesia on both heel skin and eyeball, with the sustained anesthetic effect lasting for at least 30 min. CONCLUSIONS: These findings indicate that the mosquito proboscis-inspired cambered MNs patch provides rapid and painless local anesthesia, overcoming the limitations of conventional delivery methods of local anesthetics, thus opening up new possibilities in the treatment of ophthalmic diseases.

Effects of cerebellar transcranial direct current stimulation on rehabilitation of upper limb motor function after stroke.

Background: The cerebellum is involved in the control and coordination of movements but it remains unclear whether stimulation of the cerebellum could improve the recovery of upper limb motor function. Therefore, this study aimed to explore whether cerebellar transcranial direct current stimulation (tDCS) therapy could promote the recovery of upper limb motor function in patients who suffered a stroke. Methods: In this randomized, double-blind, and sham-controlled prospective study, 77 stroke patients were recruited and randomly assigned to the tDCS group (n = 39) or the control group (n = 38). The patients received anodal (2 mA, 20 min) or sham tDCS therapy for 4 weeks. The primary outcome was the change in the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score from baseline to the first day after 4 weeks of treatment (T1) and 60 days after 4 weeks of treatment (T2). The secondary outcomes were the FMA-UE response rates assessed at T1 and T2. Adverse events (AEs) related to the tDCS treatment were also recorded. Results: At T1, the mean FMA-UE score increased by 10.7 points [standard error of the mean (SEM) = 1.4] in the tDCS group and by 5.8 points (SEM = 1.3) in the control group (difference between the two groups was 4.9 points, P = 0.013). At T2, the mean FMA-UE score increased by 18.9 points (SEM = 2.1) in the tDCS group and by 12.7 points (SEM = 2.1) in the control group (the difference between the two groups was 6.2 points, P = 0.043). At T1, 26 (70.3%) patients in the tDCS group had a clinically meaningful response to the FMA-UE score compared to 12 (34.3%) patients in the control group (the difference between the two groups was 36.0%, P =0.002). At T2, 33 (89.2%) patients in the tDCS group had a clinically meaningful response to the FMA-UE score compared with 19 (54.3%) patients in the control group (the difference between the two groups was 34.9%, P = 0.001). There was no statistically significant difference in the incidence of adverse events between the two groups. In the subgroup analysis of different hemiplegic sides, the rehabilitation effect of patients with right hemiplegia was better than that of patients with left hemiplegia (P < 0.05); in the age subgroup analysis, different age groups of patients did not show a significant difference in the rehabilitation effect (P > 0.05). Conclusion: Cerebellar tDCS can be used as an effective and safe treatment to promote recovery of upper limb motor function in stroke patients. Trial registration: ChiCTR.org.cn, identifier: ChiCTR2200061838.

Corrigendum: Aging Changes Effective Connectivity of Motor Networks During Motor Execution and Motor Imagery.

[This corrects the article DOI: 10.3389/fnagi.2019.00312.].

Effect of transcranial direct-current stimulation on cognitive function in stroke patients: A systematic review and meta-analysis.

OBJECTIVE: Transcranial direct-current stimulation (tDCS) is a noninvasive approach that can alter brain excitability. Several studies have shown the effectiveness of tDCS in improving language and movement function in stroke patients. However, the effect of tDCS on cognitive function after stroke remains uncertain. METHODS: We searched Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the China National Knowledge Infrastructure, the China Science and Technology Journal Database, and the Wanfang Data Knowledge Service Platform from inception to April 2, 2019. Two reviewers independently screened the studies, extracted the data, and evaluated the quality of the included studies using the Cochrane Collaboration Risk of Bias Tool. All statistical analyses were performed in RevMan 5.3, and the mean difference (MD) or standard mean difference (SMD) were used as the pooled statistics. RESULTS: Fifteen studies involving 820 participants were included. When compared with passive tDCS, anodal tDCS was associated with improved general cognitive performance as examined by the Minimum Mental State Examination or Montreal Cognitive Assessment (SMD = 1.31, 95% CI 0.91-1.71, P < 0.00001), attention performance (SMD = 0.66, 95% CI 0.11-1.20, P = 0.02). There was no significant difference in memory performance (SMD = 0.41, 95% CI -0.67-1.50, P = 0.46). CONCLUSIONS: tDCS is likely to be effective for patients with cognitive impairment after stroke. The evidence for different effects based on population characteristics and stimulation methods was limited, but a real effect cannot be ruled out. More high-quality research in this field is required to determine the potential benefits of tDCS in the treatment of cognitive deficits after stroke and to establish the optimal treatment program.

Aging Changes Effective Connectivity of Motor Networks During Motor Execution and Motor Imagery.

Age-related neurodegenerative and neurochemical changes are considered to be the basis for the decline of motor function; however, the change of effective connections in cortical motor networks that come with aging remains unclear. Here, we investigated the age-related changes of the dynamic interaction between cortical motor regions. Twenty young subjects and 20 older subjects underwent both right hand motor execution (ME) and right hand motor imagery (MI) tasks by using functional magnetic resonance imaging. Conditional Granger causality analysis (CGCA) was used to compare young and older adults' effective connectivity among regions of the motor network during the tasks. The more effective connections among motor regions in older adults were found during ME; however, effective within-domain hemisphere connections were reduced, and the blood oxygenation level dependent (BOLD) signal was significantly delayed in older adults during MI. Supplementary motor area (SMA) had a significantly higher In+Out degree within the network during ME and MI in older adults. Our results revealed a dynamic interaction within the motor network altered with aging during ME and MI, which suggested that the interaction with cortical motor neurons caused by the mental task was more difficult with aging. The age-related effects on the motor cortical network provide a new insight into our understanding of neurodegeneration in older individuals.

Disrupted structural and functional connectivity networks in ischemic stroke patients.

Local lesions caused by stroke may result in extensive structural and functional reorganization in the brain. Previous studies of this phenomenon have focused on specific brain networks. Here, we aimed to discover abnormalities in whole-brain networks and to explore the decoupling between structural and functional connectivity in patients with stroke. Fifteen ischemic stroke patients and 23 normal controls (NCs) were recruited in this study. A graph theoretical analysis was employed to investigate the abnormal topological properties of structural and functional brain networks in patients with stroke. Both patients with stroke and NCs exhibited small-world organization in brain networks. However, compared to NCs, patients with stroke exhibited abnormal global properties characterized by a higher characteristic path length and lower global efficiency. Furthermore, patients with stroke showed altered nodal characteristics, primarily in certain motor- and cognition-related regions. Positive correlations between the nodal degree of the inferior parietal lobule and the Fugl-Meyer Assessment (FMA) score and between the nodal betweenness centrality of the posterior cingulate gyrus (PCG) and immediate recall were observed in patients with stroke. Most importantly, the strength of the structural-functional connectivity network coupling was decreased, and the coupling degree was related to the FMA score of patients, suggesting that decoupling may provide a novel biomarker for the assessment of motor impairment in patients with stroke. Thus, the topological organization of brain networks is altered in patients with stroke, and our results provide insights into the structural and functional organization of the brain after stroke from the viewpoint of network topology.

Abnormal functional networks in resting-state of the sub-cortical chronic stroke patients with hemiplegia.

The aim of this study is to identify the properties of the motor network and the default-mode network (DMN) of the sub-cortical chronic stroke patients, and to study the relationship between the network connectivity and the neurological scales of the stroke patients. Twenty-eight chronic stroke patients (28-77days post-stroke) and twenty-eight healthy control subjects (HCs) were recruited. Independent component analysis (ICA) was performed to obtain the motor network and the DMN. Two sample t-tests was used to compare the differences of the motor network and the DMN between the patients and HCs. Additionally, correlations between the network connectivity and the behavioral scores of the stroke patients were studied. Compared with the HCs, the motor network connectivity of the stroke patients was significantly increased in the contralesional superior parietal lobule, but decreased in ipsilesional M1. The DMN connectivity of the stroke patients was significantly increased in the contralesional middle frontal gyrus, but decreased in bilateral precuneus, ipsilesional supramarginal and angular gyrus. Moreover, the motor network connectivity of the contralesional superior parietal lobule was positively correlated with the Fugl-Meyer assessment (FMA) score of the stroke patients. Our results showed abnormal motor network and DMN during the resting-state of the stroke patients, suggesting that resting-state network connectivity could serve as biomarkers for future stroke studies. Brain-behavior relationships could be taken into account while evaluating stroke patients.

Conditional Granger Causality Analysis of Effective Connectivity during Motor Imagery and Motor Execution in Stroke Patients.

Aims. Motor imagery has emerged as a promising technique for the improvement of motor function following stroke, but the mechanism of functional network reorganization in patients during this process remains unclear. The aim of this study is to evaluate the cortical motor network patterns of effective connectivity in stroke patients. Methods. Ten stroke patients with right hand hemiplegia and ten normal control subjects were recruited. We applied conditional Granger causality analysis (CGCA) to explore and compare the functional connectivity between motor execution and motor imagery. Results. Compared with the normal controls, the patient group showed lower effective connectivity to the primary motor cortex (M1), the premotor cortex (PMC), and the supplementary motor area (SMA) in the damaged hemisphere but stronger effective connectivity to the ipsilesional PMC and M1 in the intact hemisphere during motor execution. There were tighter connections in the cortical motor network in the patients than in the controls during motor imagery, and the patients showed more effective connectivity in the intact hemisphere. Conclusions. The increase in effective connectivity suggests that motor imagery enhances core corticocortical interactions, promotes internal interaction in damaged hemispheres in stroke patients, and may facilitate recovery of motor function.

Motor recovery at 6 months after admission is related to structural and functional reorganization of the spine and brain in patients with spinal cord injury.

This study aimed to explore structural and functional reorganization of the brain in the early stages of spinal cord injury (SCI) and identify brain areas that contribute to motor recovery. We studied 25 patients with SCI, including 10 with good motor recovery and 15 with poor motor recovery, along with 25 matched healthy controls. The mean period post-SCI was 9.2 ± 3.5 weeks in good recoverers and 8.8 ± 2.6 weeks in poor recoverers. All participants underwent structural and functional MRI on a 3-T magnetic resonance system. We evaluated differences in cross-sectional spinal cord area at the C2/C3 level, brain cortical thickness, white matter microstructure, and functional connectivity during the resting state among the three groups. We also evaluated associations between structural and functional reorganization and the rate of motor recovery. After SCI, compared with good recoverers, poor recoverers had a significantly decreased cross-sectional spinal cord area, cortical thickness in the right supplementary motor area and premotor cortex, and fractional anisotropy (FA) in the right primary motor cortex and posterior limb of the internal capsule. Meanwhile, poor recoverers showed decreased functional connectivity between the primary motor cortex and higher order motor areas (supplementary motor area and premotor cortex), while good recoverers showed increased functional connectivity among these regions. The structural and functional reorganization of the spine and brain was associated with motor recovery rate in all SCI patients. In conclusion, structural and functional reorganization of the spine and brain directly affected the motor recovery of SCI. Less structural atrophy and enhanced functional connectivity are associated with good motor recovery in patients with SCI. Multimodal imaging has the potential to predict motor recovery in the early stage of SCI. Hum Brain Mapp 37:2195-2209, 2016. © 2016 Wiley Periodicals, Inc.

Relationship between functional connectivity and motor function assessment in stroke patients with hemiplegia: a resting-state functional MRI study.

INTRODUCTION: Resting-state functional magnetic resonance imaging (fMRI) has been used to examine the brain mechanisms of stroke patients with hemiplegia, but the relationship between functional connectivity (FC) and treatment-induced motor function recovery has not yet been fully investigated. This study aimed to identify the brain FC changes in stroke patients and study the relationship between FC and motor function assessment using the resting-state fMRI. METHODS: Seventeen stroke patients with hemiplegia and fifteen healthy control subjects (HCSs) were recruited in this study. We compared the FC between the ipsilesional primary motor cortex (M1) and the whole brain of the patients with the FC of the HCSs and studied the FC changes in the patients before and after conventional rehabilitation and motor imagery therapy. Additionally, correlations between the FC change and motor function of the patients were studied. RESULTS: Compared to the HCSs, the FC in the patient group was significantly increased between the ipsilesional M1 and the ipsilesional inferior parietal cortex, frontal gyrus, supplementary motor area (SMA), and contralesional angular and decreased between the ipsilesional M1 and bilateral M1. After the treatment, the FC between the ipsilesional M1 and contralesional M1 increased while the FC between the ipsilesional M1 and ipsilesional SMA and paracentral lobule decreased. A statistically significant correlation was found between the FC change in the bilateral M1 and the Fugl-Meyer assessment (FMA) score change. CONCLUSION: Our results revealed an abnormal motor network after stroke and suggested that the FC could serve as a biomarker of motor function recovery in stroke patients with hemiplegia.

Age-specific activation of cerebral areas in motor imagery--a fMRI study.

INTRODUCTION: The objectives of this study were to study the age-specific activation patterns of cerebral areas during motor execution (ME) and motor imaging (MI) of the upper extremities and to discuss the age-related neural mechanisms associated with ME or MI. METHODS: The functional magnetic resonance imaging technique was used to monitor the pattern and intensity of brain activation during the ME and MI of the upper extremities in 20 elderly (>50 years) and 19 young healthy subjects (<25 years). RESULTS: No major differences were identified regarding the activated brain areas during ME or MI between the two groups; however, a minor difference was noted. The intensity of the activated brain area during ME was stronger in the older group than in the younger group, while the results with MI were the opposite. The posterior central gyrus and supplementary motor area during MI were more active in the younger group than in the older group. The putamen, lingual, and so on demonstrated stronger activation during dominant hand MI in the older group. CONCLUSION: The results of this study revealed that the brain structure was altered and that neuronal activity was attenuated with age, and the cerebral cortex and subcortical tissues were found to be over-activated to achieve the same level of ME and MI, indicating that the activating effects of the left hemisphere enhanced with age, whereas the inhibitory effects declined during ME, and activation of the right hemisphere became more difficult during MI.