Exploration of rich-club reorganization in facial synkinesis: insights from structural and functional brain network analysis.

Facial palsy therapies based on cortical plasticity are in development, but facial synkinesis progress is limited. Studying neural plasticity characteristics, especially network organization and its constitutive elements (nodes/edges), is the key to overcome the bottleneck. We studied 55 participants (33 facial synkinesis patients, 22 healthy controls) with clinical assessments, functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI). We analyzed rich-club organization and metrics of structural brain networks (rich-club coefficients, strength, degree, density, and efficiency). Functional brain network metrics, including functional connectivity and its coupling with the structural network, were also computed. Patients displayed reduced strength and density of rich-club nodes and edges, as well as decreased global efficiency. All nodes exhibited decreased nodal efficiency in patients. Patients had significantly increased functional connectivity and decreased structural-functional coupling strength in rich-club nodes, rich-club edges, and feeder edges. Our study indicates that facial synkinesis patients have weakened structural connections but enhanced functional transmission from rich-club nodes. The loss of connections and efficiency in structural network may trigger compensatory increases in functional connectivity of rich-club nodes. Two potential biomarkers, rich-club edge density and structural-functional coupling strength, may serve as indicators of disease outcome. These findings provide valuable insights into synkinesis mechanisms and offer potential targets for cortical intervention.

Prevalence and prognosis of hard-to-heal wounds with comorbidities in China.

OBJECTIVE: Regular retrospective analysis is necessary for potential improvement in clinical practice for the treatment of hard-to-heal wounds. Comorbidities and outcomes have demonstrated spatial and temporal diversity, emphasising the importance of updates in epidemiology. The complexity of healing hard-to-heal wounds has long been known, and so we sought evidence-based improvement on the current principles of treatment. METHOD: Demographic and clinical information of patients from the WoundCareLog database was collected. Patients who met the inclusion criteria and completed follow-up after treatment were included. Comorbidities were diagnosed and classified into eight categories based on ICD-10. We compared the demographic and aetiological characteristics between patients with and without comorbidities by t-test and Chi-squared test. The impact of comorbidities on wound healing were evaluated with a multivariate Cox model. RESULTS: A total of 2163 patients met the inclusion criteria and were enrolled, of whom 37.0% were aged 61-80 years, 36.0% were aged 41-60 years and 60.8% were male. The lower extremities and buttocks were the most commonly affected areas with hard-to-heal wounds. Non-traumatic wounds accounted for 66.6% of cases, and infection, pressure and diabetes were the most common causes. Paralysis and diabetes were the most important factors which led to a prolonged healing process and inferior clinical outcomes. CONCLUSION: Comorbidities of hard-to-heal wounds were treated as separate contributors and their weighted effect on outcome was calculated through correlation analysis. Paralysis and diabetes were the most unfavourable comorbidities affecting the treatment of non-traumatic hard-to-heal wounds. Our study highlighted the priority of comorbidity treatment through data-driven approaches. It provides potential value in developing better public health strategies and preventive medicine.

Identifying Modulated Functional Connectivity in Corresponding Cerebral Networks in Facial Nerve Lesions Patients With Facial Asymmetry.

Facial asymmetry is the major complaint of patients with unilateral facial nerve lesions. Frustratingly, although patients experience the same etiology, the extent of oral commissure asymmetry is highly heterogeneous. Emerging evidence indicates that cerebral plasticity has a large impact on clinical severity by promoting or impeding the progressive adaption of brain function. However, the precise link between cerebral plasticity and oral asymmetry has not yet been identified. In the present study, we performed functional magnetic resonance imaging on patients with unilateral facial nerve transections to acquire in vivo neural activity. We then identified the regions of interest corresponding to oral movement control using a smiling motor paradigm. Next, we established three local networks: the ipsilesional (left) intrahemispheric, contralesional (right) intrahemispheric, and interhemispheric networks. The functional connectivity of each pair of nodes within each network was then calculated. After thresholding for sparsity, we analyzed the mean intensity of each network connection between patients and controls by averaging the functional connectivity. For the objective assessment of facial deflection, oral asymmetry was calculated using FACEgram software. There was decreased connectivity in the contralesional network but increased connectivity in the ipsilesional and interhemispheric networks in patients with facial nerve lesions. In addition, connectivity in the ipsilesional network was significantly correlated with the extent of oral asymmetry. Our results suggest that motor deafferentation of unilateral facial nerve leads to the upregulated ipsilesional hemispheric connections, and results in positive interhemispheric inhibition effects to the contralesional hemisphere. Our findings provide preliminary information about the possible cortical etiology of facial asymmetry, and deliver valuable clues regarding spatial information, which will likely be useful for the development of therapeutic interventions.

Effective connectivity decreases in specific brain networks with postparalysis facial synkinesis: a dynamic causal modeling study.

Currently, the treatments for postparalysis facial synkinesis are still inadequate. However, neuroimaging mechanistic studies are very limited and blurred. Instead of mapping activation regions, we were devoted to characterizing the organizational features of brain regions to develop new targets for therapeutic intervention. Eighteen patients with unilateral facial synkinesis and 19 healthy controls were enrolled. They were instructed to perform task functional magnetic resonance imaging (eye blinking and lip pursing) examinations and resting-state scans. Then, we characterized group differences in task-state fMRI to identify three foci, including the contralateral precentral gyrus (PreCG), supramarginal gyrus (SMG), and superior parietal gyrus (SPG). Next, we employed a novel approach (using dynamic causal modeling) to identify directed connectivity differences between groups in different modes. Significant patterns in multiple regions in terms of regionally specific actions following synkinetic movements were demonstrated, although the resting state was not significant. The couplings from the SMG to the PreCG (p = 0.03) was significant in the task of left blinking, whereas the coupling from the SMG to the SPG (p = 0.04) was significant in the task of left smiling. We speculated that facial synkinesis affects disruption among the brain networks, and specific couplings that are modulated simultaneously can compensate for motor deficits. Therefore, behavioral or brain stimulation technique treatment could be applied to alter reorganization within specific couplings in the rehabilitation of facial function.

Structural remodeling in related brain regions in patients with facial synkinesis.

Facial synkinesis is a troublesome sequelae of facial nerve malfunction. It is difficult to recover from synkinesis, despite improved surgical techniques for isolating the peripheral facial nerve branches. Furthermore, it remains unclear whether long-term dysfunction of motor control can lead to irreversible plasticity-induced structural brain changes. This case-control study thus investigated the structural brain alterations associated with facial synkinesis. The study was conducted at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, China. Twenty patients with facial synkinesis (2 male and 18 female, aged 33.35 ± 6.97 years) and 19 healthy volunteers (2 male and 17 female, aged 33.21 ± 6.75 years) underwent magnetic resonance imaging, and voxel-based and surface-based morphometry techniques were used to analyze data. There was no significant difference in brain volume between patients with facial synkinesis and healthy volunteers. Patients with facial synkinesis exhibited a significantly reduced cortical thickness in the contralateral superior and inferior temporal gyri and a reduced sulcal depth of the ipsilateral precuneus compared with healthy volunteers. In addition, sulcal depth of the ipsilateral precuneus was negatively correlated with the severity of depression. These findings suggest that there is a structural remodeling of gray matter in patients with facial synkinesis after facial nerve malfunction. This study was approved by the Ethics Review Committee of the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, China (approval No. 2017-365-T267) on September 13, 2017, and was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800014630) on January 25, 2018.

Alteration of spatial patterns at the network-level in facial synkinesis: an independent component and connectome analysis.

BACKGROUND: The treatment of post-facial palsy synkinesis (PFPS) remains inadequate. Previous studies have confirmed that brain plasticity is involved in the process of functional restoration. Isolated activation has been well studied, however, the brain works as an integrity of several isolated regions. This study aimed to assess the alteration of the brain network topology with overall and local characteristics of information dissemination. Understanding the neural mechanisms of PFPS could help to improve therapy options and prognosis. METHODS: Patients with facial synkinesis and healthy controls (HCs) were estimated using functional magnetic resonance imaging (fMRI) of resting-state. Subsequently, an independent component analysis (ICA) was used to extract four subnets from the whole brain. Then we used the measurements of graph theory and calculated in the whole-brain network and each sub-network. RESULTS: We found no significant difference between the patient group and the HCs on the whole-brain scale. Then we identified four subnetworks from the resting-state data. In the sub-network property analysis, patients' locally distributed properties in the sensorimotor network (SMN) and ventral default mode network (vDMN) were reduced. It revealed that γ (10,000 permutations, P=0.048) and S (10,000 permutations, P=0.022) within the SMN progressively decreased in patients with PFPS. For the analysis of vDMN, significant differences were found in γ (10,000 permutations, P=0.019), Elocal (10,000 permutations, P=0.008), and ß (10,000 permutations, P=0.011) between the groups. CONCLUSIONS: Our results demonstrated a reduction in local network processing efficiency in patients with PFPS. Therefore, we speculate that decreased characteristics in the intra-vDMN and intra-SMN, rather than the whole-brain network, may serve distinct symptoms such as facial nerve damage or more synkinetic movements. This finding of the alteration of network properties is a small step forward to help uncover the underlying mechanism.

MEK1/2 Inhibitor (GDC0623) Promotes Osteogenic Differentiation of Primary Osteoblasts Inhibited by IL-1ß through the MEK-Erk1/2 and Jak/Stat3 Pathways.

OBJECTIVE: We evaluated the effects and mechanisms of GDC0623 on osteogenic differentiation of osteoblasts induced by IL-1ß. Methodology. Osteoblasts were treated with 20 ng/ml IL-1ß and 0.1 µM GDC0623. Cell proliferation levels were evaluated by the cell counting kit 8 (CCK8), EdU assay, and western blotting [proliferating cell nuclear antigen (PCNA) and Cyclin D1]. Osteoblasts were cultured in an osteogenic induction medium for 1-3 weeks after which their differentiations were assessed by alkaline phosphatase (ALP) staining, Alizarin Red staining, calcium concentration, immunocytochemistry staining, real-time quantitative PCR (RT-qPCR), and immunofluorescence staining. The osteogenesis-associated mechanisms were further evaluated by western blotting using appropriate antibodies. RESULTS: Relative to the control group, IL-1ß induced the rapid proliferation of osteoblasts and suppressed their osteogenic differentiations by upregulating the activities of MEK-Erk1/2 as well as Jak-Stat3 pathways and by elevating MMP13 and MMP9 levels. However, blocking of the MEK-Erk1/2 signaling pathway by GDC0623 treatment reversed these effects. CONCLUSION: Inhibition of Jak-Stat3 pathway by C188-9 downregulated the expression levels of MMP9 and MMP13, activated MEK-Erk1/2 pathway, and inhibited osteogenic differentiation.

Functional Organization of Brain Network in Peripheral Neural Anastomosis Rats after Electroacupuncture: An ICA and Connectome Analysis.

Acupuncture is a mild therapy in rehabilitation practice of peripheral nerve injury. Previous studies confirmed the deep participation of brain plasticity in the process of functional restoration. The therapeutic effect of acupuncture is also believed to be closely associated with brain plasticity, especially in the hypothalamus and limbic system. But the fuzzy neural mechanism somehow limits the application or improvement of this therapy. There is little information about the effect of acupuncture on topological properties of brain networks. Instead of functional segregation approach, we utilized graph theory method to analyze the large-scale and distributed properties of information processing. We first established rat model of sciatic nerve injury and performed rehabilitation therapy of electroacupuncture for 120 days. Meanwhile, we used independent component analysis to extract seven sub-networks from the whole brain. Then measurements of graph theory were calculated in each sub-network as well as the whole brain network. We found no significant difference of any measurement in whole brain network among intervention group, model group and normal group. But the assortativity, hierarchy, small-world properties of sub-network displayed significant differences among three groups. It induces changes of neural plasticity in several sub-networks instead of whole brain network. We attributed the changes to the enhancement of the short-term compensatory adaptation and the reduction of the long-term overacting regional information transmission. The present study may shed light on the vague distinction of large-scale property of brain networks after electroacupuncture, which leads to a better understanding of this ancient traditional Chinese therapy.

Acupuncture Induces Reduction in Limbic-Cortical Feedback of a Neuralgia Rat Model: A Dynamic Causal Modeling Study.

Background: Neuropathic pain after brachial plexus avulsion remained prevalent and intractable currently. However, the neuroimaging study about neural mechanisms or etiology was limited and blurred. Objective: This study is aimed at investigating the effect of electroacupuncture on effective connectivity and neural response in corticolimbic circuitries during implicit processing of nociceptive stimulus in rats with brachial plexus pain. Methods: An fMRI scan was performed in a total of 16 rats with brachial plexus pain, which was equally distributed into the model group and the electroacupuncture group. The analysis of task-dependent data determined pain-related activation in each group. Based on those results, several regions including AMY, S1, and h were recruited as ROI in dynamic causal modeling (DCM) analysis comparing evidence for different neuronal hypotheses describing the propagation of noxious stimuli in regions of interest and horizontal comparison of effective connections between the model and electroacupuncture groups. Results: In both groups, DCM revealed that noxious stimuli were most likely driven by the somatosensory cortex, with bidirectional propagation with the hypothalamus and amygdala and the interactions in them. Also, the 3-month intervention of acupuncture reduced effective connections of h-S1 and AMY-S1. Conclusions: We showed an evidence that a full connection model within the brain network of brachial plexus pain and electroacupuncture intervention reduces effective connectivity from h and AMY to S1. Our study for the first time explored the relationship of involved brain regions with dynamic causal modeling. It provided novel evidence for the feature of the organization of the cortical-limbic network and the alteration caused by acupuncture.

Diffusional plasticity induced by electroacupuncture intervention in rat model of peripheral nerve injury.

Electroacupuncture (EA) is an adjuvant therapy for peripheral nerve injury (PNI). Both peripheral and central alterations contribute to the rehabilitation process. We employed diffusion tensor imaging (DTI) to investigate the diffusion plasticity of afferent and efferent pathways caused by EA in model of peripheral nerve injury and reparation. Twenty-four rats were divided into three groups: normal group, model group and intervention group. Rats of the model group and the intervention group underwent sciatic nerve transection and anastomosis. EA intervention was performed on the intervention group at ST-36 and GB-30 for three months. Gait assessment and DTI were conducted at days post-operative (DPO) 30, 60 and 90. We selected corticospinal tract, spinothalamic tract and internal capsule as regions of interest and analyzed diffusion metrics including fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD). FA values and RD values displayed significant differences or obvious tendency while AD values maintained a stable level. RD values displayed better indicative performance than FA in internal capsule. The intervention group presented significant correlation between RD values and Regularity Index (RI) during the intervention period. The effect of EA on peripheral nerve injury repairing rats appeared to be accelerated recovery process of sensory and motor neural pathway. We proposed that RD was a potential in vivo indicator for structural plasticity caused by EA and PNI.

Evaluation of Neuropathic Pain in a Rat Model of Total Brachial Plexus Avulsion from Behavior to Brain Metabolism.

BACKGROUND: Approximately 30% to 80% of patients with brachial plexus avulsion (BPA) developed neuropathic pain. It is an intolerable neuropathic pain, which brings heavy burden to family and society. In addition to motor and sensory deficits, neuropathic pain can be another serious sequela that equally influences the patient. The development of a microsurgical technique has promoted the treatment and rehabilitation of brachial plexus injury, but pain relief after BPA is still a difficult problem. OBJECTIVES: The present study aimed to semi-quantify changes in the behavior, spinal cord and cerebral metabolism in a neuropathic pain model following BPA injury in rats. STUDY DESIGN: Controlled animal study. SETTING: Institute of Rehabilitation Medicine, Shanghai, China. METHODS: A total of 15 Sprague-Dawley rats, weighing 200 to 220 g, were randomly divided into 2 groups: experimental group (n = 10) and control group (n = 5). In the experimental group, neuropathic pain induced by BPA was established by directly avulsing the C5, C6, C7, C8, and T1 roots on the right side from the spinal cord. Rats in the control group only received open-close surgery. The autotomic behavior of biting their own digits was recorded and scored at 2 months after the surgery. Small animal positron emission tomography/computed tomography (PET/CT) images after injection of a 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) tracer were acquired to evaluate glucose metabolism in pain-related brain regions before and after the surgery, respectively. Semi-quantitative values of cortical to cerebellum standardized uptake value (SUV) ratios were calculated. Then, the animals were euthanized and the cervical segments of the spinal cord were removed for detection of glial fibrillary acidic protein (GFAP) expression in the astrocytes by immunohistochemical assay. RESULTS: Nine of the 10 rats (90%) in the experimental group showed autotomic behavior at 2 months after the surgery. Slight autotomic behavior was noted only in one of 5 rats (20%) from the control group. The autotomic score in the experimental group was significantly higher than that in the control group (5.4 ± 1.0 vs. 0.2 ± 0.4, P < 0.05). The experimental group showed significantly higher SUV ratio in both the right and left thalamus, compared to the control group (P < 0.05). Immunohistochemical assay demonstrated that GFAP positive astrocytes in the dorsal horn at the injured side significantly increased compared to the control group (P < 0.05). LIMITATIONS: There are differences between small animals and human beings, and the structure and function of the human brain is more complex than in rodents. Therefore, extrapolation of the present conclusion should be cautious. CONCLUSIONS: The present study reported a unique model of neuropathic pain following total BPA in rodents, which was demonstrated by a higher rate and score of autotomic behavior. More astrocytes were found activated in the spinal cord at the corresponding level of C5 and C6 spinal cord. In the small animal PET/CT imaging, significantly higher standardized glucose metabolic activity was found in both the right and left thalamus in the experimental group. The present study semi-quantified the neuropathic pain behavior in rats and explored the plastic changes in the spinal and brain metabolism. KEY WORDS: Brachial plexus avulsion, small animal PET/CT, glucose metabolism, neuropathic pain, astrocyte, 18F-FDG.

Motor Control Deficits in Facial Synkinesis Patients: Neuroimaging Evidences of Cerebral Cortex Involvement.

Objective: Facial synkinesis is a severe sequelae of facial nerve malfunction. Once the synkinesis is established, it is extremely difficult for patients to recover. Given that the restoration of motor or sensory function after peripheral nerve injury was closely related with cortical plasticity, we investigated cortical plasticity in facial synkinesis patients by the frequency-specific data which remains largely uncharacterized. Materials and Methods: Resting-state fMRI was conducted in 20 facial synkinesis patients and 19 healthy controls, and the amplitude of low-frequency fluctuation (ALFF) in five different frequency bands (slow-6: 0-0.01 Hz; slow-5: 0.01-0.027 Hz; slow-4: 0.027-0.073 Hz; slow-3: 0.073-0.167 Hz; and slow-2: 0.167-0.25 Hz) was calculated, respectively. And the relationship between ALFF and clinical outcomes was also analyzed. Results: Comparing with the healthy controls, facial synkinesis patients showed significantly different ALFF values, mainly in the sensorimotor areas. Furthermore, increased ALFF of the ipsilateral insula in the slow-6 band was significantly related with better facial nerve function. Conclusion: Increased ALFF values in the ipsilateral insula might reflect an abnormal state of hypercompensation in motor control of facial synkinesis patients. It provided valuable spatial information about the functionally aberrant regions, which implied the possible involvement of motor control system in facial synkinesis.

Alteration of metabolic connectivity in a rat model of deafferentation pain: a 18F-FDG PET/CT study.

OBJECTIVE: Refractory deafferentation pain has been evidenced to be related to central nervous system neuroplasticity. In this study, the authors sought to explore the underlying glucose metabolic changes in the brain after brachial plexus avulsion, particularly metabolic connectivity. METHODS: Rats with unilateral deafferentation following brachial plexus avulsion, a pain model of deafferentation pain, were scanned by small-animal 2-deoxy-[18F]fluoro-d-glucose (18F-FDG) PET/CT to explore the changes of metabolic connectivity among different brain regions. Thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) of the intact forepaw were also measured for evaluating pain sensitization. Brain metabolic connectivity and TWL were compared from baseline to 1 week after brachial plexus avulsion. RESULTS: Alterations of metabolic connectivity occurred not only within the unilateral hemisphere contralateral to the injured forelimb, but also in the other hemisphere and even in the connections between bilateral hemispheres. Metabolic connectivity significantly decreased between sensorimotor-related areas within the left hemisphere (contralateral to the injured forelimb) (p < 0.05), as well as between areas across bilateral hemispheres (p < 0.05). Connectivity between areas within the right hemisphere (ipsilateral to the injured forelimb) significantly increased (p = 0.034). TWL and MWT of the left (intact) forepaw after surgery were significantly lower than those at baseline (p < 0.001). CONCLUSIONS: This study revealed that unilateral brachial plexus avulsion facilitates pain sensitization in the opposite limb. A specific pattern of brain metabolic changes occurred in this procedure. Metabolic connectivity reorganized not only in the sensorimotor area corresponding to the affected forelimb, but also in extensive areas involving the bilateral hemispheres. These findings may broaden our understanding of central nervous system changes, as well as provide new information and a potential intervention target for nosogenesis of deafferentation pain.

The Localization Research of Brain Plasticity Changes after Brachial Plexus Pain: Sensory Regions or Cognitive Regions?

Objective: Neuropathic pain after brachial plexus injury remains an increasingly prevalent and intractable disease due to inadequacy of satisfactory treatment strategies. A detailed mapping of cortical regions concerning the brain plasticity was the first step of therapeutic intervention. However, the specific mapping research of brachial plexus pain was limited. We aimed to provide some localization information about the brain plasticity changes after brachial plexus pain in this preliminary study. Methods: 24 Sprague-Dawley rats received complete brachial plexus avulsion with neuropathic pain on the right forelimb successfully. Through functional imaging of both resting-state and block-design studies, we compared the amplitude of low-frequency fluctuations (ALFF) of premodeling and postmodeling groups and the changes of brain activation when applying sensory stimulation. Results: The postmodeling group showed significant decreases on the mechanical withdrawal threshold (MWT) in the bilateral hindpaws and thermal withdrawal latency (TWL) in the left hindpaw than the premodeling group (P < 0.05). The amplitude of low-frequency fluctuations (ALFF) of the postmodeling group manifested increases in regions of the left anterodorsal hippocampus, left mesencephalic region, left dorsal midline thalamus, and so on. Decreased ALFF was observed in the bilateral entorhinal cortex compared to that of the premodeling group. The results of block-design scan showed significant differences in regions including the limbic/paralimbic system and somatosensory cortex. Conclusion: We concluded that the entorhinal-hippocampus pathway, which was part of the Papez circuit, was involved in the functional integrated areas of brachial plexus pain processing. The regions in the "pain matrix" showed expected activation when applying instant nociceptive stimulus but remained silent in the resting status. This research confirmed the involvement of cognitive function, which brought novel information to the potential new therapy for brachial plexus pain.

Cerebral 18F-FDG metabolism alteration in a neuropathic pain model following brachial plexus avulsion: A PET/CT study in rats.

The present study aimed to investigate cerebral metabolic changes in a neuropathic pain model following deafferentation. A total of 24 Sprague-Dawley rats were included for modeling of right brachial plexus avulsion (BPA) through the posterior approach. As nerve injury would cause central sensitization and facilitate pain sensitivity in other parts of the body, thermal withdrawal latency (TWL) of the intact forepaw was assessed to investigate the level of pain perception following BPA-induced neuropathic pain. [Fluorine-18]-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography (PET) was applied to the brain before and after brachial plexus avulsion to explore metabolic changes in neuropathic pain following deafferentation. The TWL of the left (intact) forepaw was significantly lower after BPA than that of baseline (p < 0.001). Using TWL as a covariate, standardized uptake values (SUVs) of 18F-FDG significantly increased in the ipsilateral dorsolateral thalamus and contralateral anterodorsal hippocampus after BPA. Conversely, SUVs in multiple brain regions decreased, including the contralateral somatosensory cortex, ipsilateral cingulate cortex, and ipsilateral temporal association cortex. The Pearson correlation analysis showed that the SUVs of the contralateral anterodorsal hippocampus and ipsilateral dorsolateral thalamus were negatively related to the TWL of the intact forepaw, whereas the SUVs in the contralateral somatosensory cortex and ipsilateral cingulate cortex were positively related to it (p < 0.05). These findings indicate that upregulation of metabolism in the anterodorsal hippocampus and dorsolateral thalamus and downregulation metabolism in the contralateral somatosensory cortex and ipsilateral cingulate cortex could be a unique pattern of metabolic changes for neuropathic pain following brachial plexus avulsion.

Small-worldness of brain networks after brachial plexus injury: A resting-state functional magnetic resonance imaging study.

Research on brain function after brachial plexus injury focuses on local cortical functional reorganization, and few studies have focused on brain networks after brachial plexus injury. Changes in brain networks may help understanding of brain plasticity at the global level. We hypothesized that topology of the global cerebral resting-state functional network changes after unilateral brachial plexus injury. Thus, in this cross-sectional study, we recruited eight male patients with unilateral brachial plexus injury (right handedness, mean age of 27.9 ± 5.4 years old) and eight male healthy controls (right handedness, mean age of 28.6 ± 3.2). After acquiring and preprocessing resting-state magnetic resonance imaging data, the cerebrum was divided into 90 regions and Pearson's correlation coefficient calculated between regions. These correlation matrices were then converted into a binary matrix with affixed sparsity values of 0.1-0.46. Under sparsity conditions, both groups satisfied this small-world property. The clustering coefficient was markedly lower, while average shortest path remarkably higher in patients compared with healthy controls. These findings confirm that cerebral functional networks in patients still show small-world characteristics, which are highly effective in information transmission in the brain, as well as normal controls. Alternatively, varied small-worldness suggests that capacity of information transmission and integration in different brain regions in brachial plexus injury patients is damaged.

Cortical remodeling after electroacupuncture therapy in peripheral nerve repairing model.

Electroacupuncture (EA) is an alternative therapy for peripheral nerve injury (PNI). The treatment relies on post-therapeutic effect rather than real-time effect. We utilized fMRI to clarify the resting-state alteration caused by sustained effect of EA on peripheral nerve repairing model. Twenty-four rats were divided equally into three groups: normal group, model group and intervention group. Rats of the model and intervention group underwent sciatic nerve transection and direct anastomosis. EA intervention at ST-36 and GB-30 was conducted continuously for 4 months on the intervention group. Behavioral assessments and fMRI were performed 1 month and 4 months after surgery. Intervention group showed significant improvement on the gait parameters max contact mean intensity (MCMI) and thermal withdrawal latency (TWL) than model group. EA-related sustained effects of amplitude of low frequency fluctuations (ALFF) could be described as a remolding pattern of somatosensory area and sensorimotor integration regions which presented higher ALFF in the contralateral hemisphere and lower in the ipsilateral hemisphere than model group. Interhemispheric functional connectivity (FC) analysis showed a significantly lower FC after EA therapy between the largest significantly different clusters in bilateral somatosensory cortices than the model group 4 months after surgery(p < 0.05). And the model group presented significantly higher FC than the normal group at both two time-points (p < 0.01). The sustained effect of EA on peripheral nerve repairing rats appeared to induce both regional and extensive neuroplasticity in bilateral hemispheres. We proposed that such EA-related effect was a reverse of maladaptive plasticity caused by PNI.

A Longitudinal Mapping Study on Cortical Plasticity of Peripheral Nerve Injury Treated by Direct Anastomosis and Electroacupuncture in Rats.

OBJECTIVE: We used functional magnetic resonance imaging to provide a longitudinal description of cortical plasticity caused by electroacupuncture (EA) of sciatic nerve transection and direct anastomosis in rats. METHODS: Sixteen rats in a sciatic nerve transection and direct anastomosis model were randomly divided into intervention and control groups. EA intervention in the position of ST-36, GB-30 was conducted continuously for 4 months in the intervention group. Functional magnetic resonance imaging and gait assessment were performed every month after intervention. RESULTS: The somatosensory area was more activated in the first 2 months and then deactivated in the rest 2 months when EA was applied. The pain-related areas had the same activation pattern as the somatosensory area. The limbic/paralimbic areas fluctuated more during the EA intervention, which was not constantly activated or deactivated as previous studies reported. We attributed such changes in somatosensory and pain-related areas to the gradual reduction of sensory afferentation. The alterations in limbic/paralimbic system might be associated with the confrontation between the upregulating effect of paresthesia or pain and the downregulating effect of EA intervention through the autonomic nerve system. The gait analysis showed significantly higher maximum contact mean intensity in the intervention group. CONCLUSIONS: The alterations in the brain brought about by the long-term therapeutic effect of EA could be described as a synchronized activation pattern in the somatosensory and pain-related areas and a fluctuating pattern in the limbic/paralimbic system.

Trial of Contralateral Seventh Cervical Nerve Transfer for Spastic Arm Paralysis.

BACKGROUND: Spastic limb paralysis due to injury to a cerebral hemisphere can cause long-term disability. We investigated the effect of grafting the contralateral C7 nerve from the nonparalyzed side to the paralyzed side in patients with spastic arm paralysis due to chronic cerebral injury. METHODS: We randomly assigned 36 patients who had had unilateral arm paralysis for more than 5 years to undergo C7 nerve transfer plus rehabilitation (18 patients) or to undergo rehabilitation alone (18 patients). The primary outcome was the change from baseline to month 12 in the total score on the Fugl-Meyer upper-extremity scale (scores range from 0 to 66, with higher scores indicating better function). Results The mean increase in Fugl-Meyer score in the paralyzed arm was 17.7 in the surgery group and 2.6 in the control group (difference, 15.1; 95% confidence interval, 12.2 to 17.9; P<0.001). With regard to improvements in spasticity as measured on the Modified Ashworth Scale (an assessment of five joints, each scored from 0 to 5, with higher scores indicating more spasticity), the smallest between-group difference was in the thumb, with 6, 9, and 3 patients in the surgery group having a 2-unit improvement, a 1-unit improvement, or no change, respectively, as compared with 1, 6, and 7 patients in the control group (P=0.02). Transcranial magnetic stimulation and functional imaging showed connectivity between the ipsilateral hemisphere and the paralyzed arm. There were no significant differences from baseline to month 12 in power, tactile threshold, or two-point discrimination in the hand on the side of the donor graft. RESULTS: The mean increase in Fugl-Meyer score in the paralyzed arm was 17.7 in the surgery group and 2.6 in the control group (difference, 15.1; 95% confidence interval, 12.2 to 17.9; P<0.001). With regard to improvements in spasticity as measured on the Modified Ashworth Scale (an assessment of five joints, each scored from 0 to 5, with higher scores indicating more spasticity), the smallest between-group difference was in the thumb, with 6, 9, and 3 patients in the surgery group having a 2-unit improvement, a 1-unit improvement, or no change, respectively, as compared with 1, 6, and 7 patients in the control group (P=0.02). Transcranial magnetic stimulation and functional imaging showed connectivity between the ipsilateral hemisphere and the paralyzed arm. There were no significant differences from baseline to month 12 in power, tactile threshold, or two-point discrimination in the hand on the side of the donor graft. CONCLUSIONS: In this single-center trial involving patients who had had unilateral arm paralysis due to chronic cerebral injury for more than 5 years, transfer of the C7 nerve from the nonparalyzed side to the side of the arm that was paralyzed was associated with a greater improvement in function and reduction of spasticity than rehabilitation alone over a period of 12 months. Physiological connectivity developed between the ipsilateral cerebral hemisphere and the paralyzed hand. (Funded by the National Natural Science Foundation of China and others; Chinese Clinical Trial Registry number, 13004466 .).

Local and Extensive Neuroplasticity in Carpal Tunnel Syndrome: A Resting-State fMRI Study.

Carpal tunnel syndrome (CTS) is a most common peripheral nerve entrapment neuropathy characterized by sensorimotor deficits in median nerve innervated digits. Block-design task-related functional magnetic resonance imaging (fMRI) studies have been used to investigate CTS-related neuroplasticity in the primary somatosensory cortices. However, considering the persistence of digital paresthesia syndrome caused by median nerve entrapment, spontaneous neuronal activity might provide a better understanding of CTS-related neuroplasticity, which remains unexplored. The present study aimed to investigate both local and extensive spontaneous neuronal activities with resting-state fMRI. A total of 28 bilateral CTS patients and 24 normal controls were recruited, and metrics, including amplitude of low-frequency fluctuation (ALFF) and voxel-wise functional connectivity (FC), were used to explore synaptic activity at different spatial scales. Correlations with clinical measures were further investigated by linear regression. Decreased amplitudes of low-frequency fluctuation were observed in the bilateral primary sensory cortex (SI) and secondary sensory cortex (SII) in CTS patients (AlphaSim corrected P < .05). This was found to be negatively related to the sensory thresholds of corresponding median nerve innervated fingers. In the voxel-wise FC analysis, with predefined seed regions of interest in the bilateral SI and primary motor cortex, we observed decreased interhemispheric and increased intrahemispheric FC. Additionally, both interhemispheric and intrahemispheric FC were found to be significantly correlated with the mean ALFF.