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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.

Pain is one of the manifestations of hip disorder and has been proven to lead to the remodeling of somatotopic map plasticity in the cortex. However, most studies are volume-based which may lead to inaccurate anatomical positioning of functional data. The methods that work on the cortical surface may be more sensitive than those using the full brain volume and thus be more suitable for map plasticity study. In this prospective cross-sectional study performed in Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, China, 20 patients with osteonecrosis of the femoral head (12 males and 8 females, aged 56.80 ± 13.60 years) and 20 healthy controls (9 males and 11 females, aged 54.56 ± 10.23 years) were included in this study. Data of resting-state functional magnetic resonance imaging were collected. The results revealed that compared with healthy controls, compared with the healthy controls, patients with osteonecrosis of the femoral head (ONFH) showed significantly increased surface-based regional homogeneity (ReHo) in areas distributed mainly in the left dorsolateral prefrontal cortex, frontal eye field, right frontal eye field, and the premotor cortex and decreased surface-based ReHo in the right primary motor cortex and primary sensory cortex. Regions showing significant differences in surface-based ReHo values between the healthy controls and patients with ONFH were defined as the regions of interests. Seed-based functional connectivity was performed to investigate interregional functional synchronization. When the areas with decreased surface-based ReHo in the frontal eye field and right premotor cortex were used as the regions of interest, compared with the healthy controls, the patients with ONFH displayed increased functional connectivity in the right middle frontal cortex and right inferior parietal cortex and decreased functional connectivity in the right precentral cortex and right middle occipital cortex. Compared with healthy controls, patients with ONFH showed significantly decreased cortical thickness in the para-insular area, posterior insular area, anterior superior temporal area, frontal eye field and supplementary motor cortex and reduced volume of subcortical gray matter nuclei in the right nucleus accumbens. These findings suggest that hip disorder patients showed cortical plasticity changes, mainly in sensorimotor- and pain-related regions. This study was approved by the Medical Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine (approval No. 2018-041) on August 1, 2018.

Xiang-Xin Xing,1,2,* Xu-Yun Hua,3,4,* Mou-Xiong Zheng,3,* Jia-Jia Wu,2 Bei-Bei Huo,1,2 Jie Ma,1,2 Zhen-Zhen Ma,1,2 Si-Si Li,1,2 Jian-Guang Xu1 1School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Rehabilitation Medicine, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Traumatology and Orthopedics, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Yangzhi Rehabilitation Hospital, Tongji University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian-Guang XuSchool of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai, People’s Republic of ChinaTel +86-21-51322091Fax +86-21-51322042Email xjg@shutcm.edu.cnIntroduction: Numerous resting-state functional magnetic resonance imaging (fMRI) researches have indicated that large-scale functional and structural remodeling occurs in the whole brain despite an intact sensorimotor network after carpal tunnel syndrome (CTS). Investigators aimed to explore alterations of the global and nodal properties that occur in the whole brain network of patients with CTS based on topographic theory.Methods: Standard-compliant fMRI data were collected from 27 patients with CTS in bilateral hands and 19 healthy control subjects in this cross-sectional study. The statistics based on brain networks were calculated the differences between the patients and the healthy. Several topological properties were computed, such as the small-worldness, nodal clustering coefficient, characteristic path length, and degree centrality.Results: Compared to those of the healthy controls, the global properties of the CTS group exhibited a decreased characteristic path length. Changes in the local-level properties included a decreased nodal clustering coefficient in 6 separate brain regions and significantly different degree centrality in several brain regions that were related to sensorimotor function and pain.Discussion: The study suggested that CTS reinforces global connections and makes their networks more random. The changed nodal properties were affiliated with basal ganglia-thalamo-cortical circuits and the pain matrix. These results provided new insights for improving our understanding of abnormal topological theory in relation to the functional brain networks of CTS patients.Perspective: This article presents that the CTS patients’ brain with a higher global efficiency. And the significant alterations in several brain regions which are more related to pain and motor processes. The results provided effective complements to the neural mechanisms underlying CTS.Keywords: small-worldness, nodal clustering coefficient, degree centrality, pain, circuits

OBJECTIVERefractory 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.METHODSRats 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.RESULTSAlterations 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).CONCLUSIONSThis 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.

Structural remodeling is a classic manifestation of disease decompensation. Facial synkinesis is the most troubling sequela of peripheral facial neuritis, and its structural remodeling, especially in white matter (WM), is still poorly understood. Therefore, understanding WM microstructure is important for predicting WM pathology and for early intervention in facial synkinesis patients. A total of 20 facial synkinesis patients (18 men and 2 women; mean age, 33.35 ± 6.97 years old) and 19 healthy controls (17 men and 2 women; mean age, 33.21 ± 6.75 years old) were enrolled in this study. rs-fMRI data, diffusion tensor imaging (DTI) data, and Beck’s Depression Inventory (BDI) data were collected, and tract-based spatial statistics (TBSS) and voxel-mirrored homotopic connectivity (VMHC) values were used to analyze changes in WM microstructure and interhemispheric coordination. Compared with the healthy controls, facial synkinesis patients exhibited significantly lower regional fractional anisotropy (FA) in the genu of the corpus callosum and the body of the corpus callosum, significantly higher regional FA in the retrolenticular part of the internal capsule, and significantly decreased VMHC values bilaterally in the orbital inferior frontal gyri, the fusiform gyri, the superior temporal gyri, the superior frontal gyri, and the supplementary motor areas. Furthermore, a lower regional FA in the genu of the corpus callosum was correlated with higher BDI scores in facial synkinesis patients. Structural remodeling, especially changes in white matter microstructure, may be the central mechanism for severe sequelae of peripheral facial neuritis.

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

Neuropathic pain has been found to be related to profound reorganization in the function and structure of the brain. We previously demonstrated changes in local brain activity and functional/metabolic connectivity among selected brain regions by using neuroimaging methods. The present study further investigated large-scale metabolic brain network changes in 32 Sprague–Dawley rats with right brachial plexus avulsion injury (BPAI). Graph theory was applied in the analysis of 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) PET images. Inter-subject metabolic networks were constructed by calculating correlation coefficients. Global and nodal network properties were calculated and comparisons between pre- and post-BPAI (7 days) status were conducted. The global network properties (including global efficiency, local efficiency and small-world index) and nodal betweenness centrality did not significantly change for all selected sparsity thresholds following BPAI (p > 0.05). As for nodal network properties, both nodal degree and nodal efficiency measures significantly increased in the left caudate putamen, left medial prefrontal cortex, and right caudate putamen (p < 0.001). The right entorhinal cortex showed a different nodal degree (p < 0.05) but not nodal efficiency. These four regions were selected for seed-based metabolic connectivity analysis. Strengthened connectivity was found among these seeds and distributed brain regions including sensorimotor area, cognitive area, and limbic system, etc. (p < 0.05). Our results indicated that the brain had the resilience to compensate for BPAI-induced neuropathic pain. However, the importance of bilateral caudate putamen, left medial prefrontal cortex, and right entorhinal cortex in the network was strengthened, as well as most of their connections with distributed brain regions.

Ischemic stroke is an acute cerebrovascular disease characterized by high mortality, morbidity and disability rates. Ischemia/reperfusion is a critical pathophysiological basis of motor and cognitive dysfunction caused by ischemic stroke. Microglia, innate immune cells of the central nervous system, mediate the neuroinflammatory response to ischemia/reperfusion. PlexinA2 (PLXNA2) plays an important role in the regulation of neuronal axon guidance, the immune response and angiogenesis. However, it is not clear whether PLXNA2 regulates microglia polarization in ischemic stroke or the underlying mechanism. In the present study, we investigated the role of PLXNA2 in rats with middle cerebral artery occlusion/reperfusion (MCAO/R) and BV2 microglia cells with oxygen and glucose deprivation/reoxygenation (OGD/R). A battery of behavioral tests, including the beam balance test, forelimb placement test, foot fault test, cylinder test, CatWalk gait analysis and Morris water maze test were performed to evaluate sensorimotor function, locomotor activity and cognitive ability. The expression of M1/M2-specific markers in the ischemic penumbra and BV2 microglia cells was detected using immunofluorescence staining, quantitative real-time PCR analysis and Western blot analysis. Our study showed that PLXNA2 knockdown accelerated the recovery of motor function and cognitive ability after MCAO/R. In addition, PLXNA2 knockdown restrained proinflammatory cytokine release and promoted anti-inflammatory cytokine release, and the mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) pathway was involved in PLXNA2 regulated microglia polarization. Taken together, our results indicate that PLXNA2 knockdown reduces neuroinflammation by switching the microglia phenotype from M1 to M2 in the ischemic penumbra of MCAO/R-injured rats, which may be due to the inhibition of mTOR/STAT3 signaling. Treatments targeting PLXNA2 may be a promising therapeutic strategy for ischemic stroke.

Carpal tunnel syndrome (CTS) is a common peripheral entrapment neuropathy. However, CTS-related changes of brain structural covariance and structural covariance networks (SCNs) patterns have not been clearly studied.To explore CTS-related brain changes from perspectives of structural connectivity and SCNs.Brain structural magnetic resonance images were acquired from 27 CTS patients and 19 healthy controls (HCs). Structural covariance and SCNs were constructed based on gray matter volume. The global network properties including clustering coefficient (Cp), characteristic path length (Lp), small-worldness index, global efficiency (Eglob), and local efficiency (Eloc) and regional network properties including degree, betweenness centrality (BC), and Eloc of a given node were calculated with graph theoretical analysis.Compared with HCs, the strength of structural connectivity between the dorsal anterior insula and medial prefrontal thalamus decreased (P .001) in CTS patients. There was no intergroup difference of area under the curve for Cp, Lp¸ Eglob, and Eloc (all P .05). The real-world SCN of CTS patients showed a small-world topology ranging from 2% to 32%. CTS patients showed lower nodal degrees of the dorsal anterior insula and medial prefrontal thalamus, and higher Eloc of a given node and BC in the lateral occipital cortex (P .001) and the dorsolateral middle temporal gyrus (P .001) than HCs, respectively.CTS had a profound impact on brain structures from perspectives of structural connectivity and SCNs.

Background Pain, a major symptom of osteonecrosis of the femoral head (ONFH), is a complex sensory and emotional experience that presents therapeutic challenges. Pain can cause neuroplastic changes at the cortical level, leading to central sensitization and difficulties with curative treatments; however, whether changes in structural and functional plasticity occur in patients with ONFH remains unclear. Methods A total of 23 ONFH inpatients who did not undergo surgery (14 males, nine females; aged 55.61 ± 13.79 years) and 20 controls (12 males, eight females; aged 47.25 ± 19.35 years) were enrolled. Functional indices of the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and a structural index of tract-based spatial statistics (TBSS) were calculated for each participant. The probability distribution of fiber direction was determined according to the ALFF results. Results ONFH patients demonstrated increased ALFF in the bilateral dorsolateral superior frontal gyrus, right medial superior frontal gyrus, right middle frontal gyrus, and right supplementary motor area. In contrast, ONFH patients showed decreased ReHo in the left superior parietal gyrus and right inferior temporal gyrus. There were no significant differences in TBSS or probabilistic tractography. Conclusion These results indicate cerebral pain processing in ONFH patients. It is advantageous to use functional magnetic resonance imaging to better understand pain pathogenesis and identify new therapeutic targets in ONFH patients.

Purpose. This study is aimed at investigating brain structural changes and structural network properties in complete spinal cord injury (SCI) patients, as well as their relationship with clinical variables. Materials and Methods. Structural MRI of brain was acquired in 24 complete thoracic SCI patients ( 38.50 ± 11.19 years, 22 males) within the first postinjury year, while 26 age- and gender-matched healthy participants ( 38.38 ± 10.63 years, 24 males) were enrolled as control. The voxel-based morphometry (VBM) approach and graph theoretical network analysis based on cross-subject grey matter volume- (GMV-) based structural covariance networks (SCNs) were conducted to investigate the impact of SCI on brain structure. Partial correlation analysis was performed to explore the relationship between the GMV of structurally changed brain regions and SCI patients’ clinical variables, including injury duration, injury level, Visual Analog Scale (VAS), American Spinal Injury Association Impairment Scale (AIS), International Classification of Functioning, Disability and Health (ICF) scale, Self-rating Depression Scale (SDS), and Self-rating Anxiety Scale (SAS), after removing the effects of age and gender. Results. Compared with healthy controls, SCI patients showed higher SDS score ( t = 4.392 and p < 0.001 ). In the VBM analysis, significant GMV reduction was found in the left middle frontal cortex, right superior orbital frontal cortex (OFC), and left inferior OFC. No significant difference was found in global network properties between SCI patients and healthy controls. In the regional network properties, significantly higher betweenness centrality (BC) was noted in the right anterior cingulum cortex (ACC) and left inferior OFC and higher nodal degree and efficiency in bilateral middle OFCs, while decreased BC was noted in the right putamen in SCI patients. Only negative correlation was found between GMV of right middle OFC and SDS score in SCI patients ( r = − 0.503 and p = 0.017 ), while no significant correlation between other abnormal brain regions and any of the clinical variables (all p > 0.05 ). Conclusions. SCI patients would experience depressive and/or anxious feelings at the early stage. Their GMV reduction mainly involved psychology-cognition related rather than sensorimotor brain regions. The efficiency of regional information transmission in psychology-cognition regions increased. Greater GMV reduction in psychology region was related with more severe depressive feelings. Therefore, early neuropsychological intervention is suggested to prevent psychological and cognitive dysfunction as well as irreversible brain structure damage.

Objectives: As one of the most objectionable sequelae of facial paralysis, patients with facial synkinesis are more likely to be depressed and have lower quality of life than other facial paralysis patients. However, there is no research on the spatial patterns of intrinsic brain activity and functional connectivity in these patients. The objective of this study was to investigate the spatial patterns and cerebral plasticity of facial synkinesis patients.Methods: A total of 20 facial synkinesis patients (18 men and 2 women; mean age: 33.35 ± 6.97 years old) and 19 healthy controls (17 men and 2 women; mean age: 33.21 ± 6.75 years old) were enrolled in this study. resting-state functional magnetic resonance imaging (rs-fMRI) data were collected, and the amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) were calculated for each participant. Two-sample t-tests were performed to compare the ALFF, ReHo, and DC maps between the two groups.Results: Compared with the healthy controls, facial synkinesis patients exhibited decreased ALFF in the fusiform gyrus, lingual gyrus, parahippocampal gyrus, triangular inferior frontal gyrus, precentral gyrus, postcentral gyrus, cingulate gyrus, superior frontal gyrus, precuneus, caudate nucleus and thalamus; decreased ReHo in the cingulate gyrus, superior frontal gyrus, insula, superior temporal gyrus, orbital middle frontal gyrus, caudate nucleus and thalamus; and decreased DC in the frontal lobe, insula, cingulate gyrus, superior temporal gyrus, lenticular putamen, hippocampus and parahippocampal gyrus. We found significant overlap in the superior frontal gyrus across the ALFF, ReHo and DC analyses.Conclusions: In facial synkinesis patients, the neurological activity in brain areas is reduced and the local synchronization in motion-related brain regions is decreased. The superior frontal gyrus could be a crucial region in the unique spatial patterns of intrinsic brain activity and functional connectivity in these patients.

Objective: The present study aimed to investigate the analgesic effect of electroacupuncture (EA) in neuropathic pain due to brachial plexus avulsion injury (BPAI) and related changes in the metabolic brain connectivity.Methods: Neuropathic pain model due to BPAI was established in adult female Sprague–Dawley rats. EA stimulations (2/15 Hz, 30 min/day, 5-day intervention followed by 2-day rest in each session) were applied to the fifth–seventh cervical “Jiaji” acupoints on the noninjured side from 1st to 12th weeks following BPAI (EA group, n = 8). Three control groups included sham EA (nonelectrical acupuncture applied to 3 mm lateral to the real “Jiaji” acupoints), BPAI-only, and normal rats (no particular intervention; eight rats in each group). Thermal withdrawal latency (TWL) of the noninjured forepaw was regularly tested to evaluate the threshold of thermalgesia. Small animal [fluorine-18]-fluoro-2-deoxy-D-glucose (18F-FDG) PET/CT scans of brain were conducted at the end of 4th, 12th, and 16th weeks to explore metabolic alterations of brain.Results: In the EA group, the TWL of the noninjured forepaw significantly decreased following BPAI and then increased following EA stimulation, compared with sham EA (P < 0.001). The metabolic brain connectivity among somatosensory cortex (SC), motor cortex (MC), caudate putamen (Cpu), and dorsolateral thalamus (DLT) in bilateral hemispheres decreased throughout the 16 weeks’ observation in the BPAI-only group, compared with the normal rats (P < 0.05). In the EA group, the strength of connectivity among the above regions were found to be increased at the end of 4th week following BPAI modeling, decreased at 12th week, and then increased again at 16th week (P < 0.05). The changes in metabolic connectivity were uncharacteristic and dispersed in the sham EA group.Conclusion: The study revealed long-term and extensive changes of metabolic brain connectivity in EA-treated BPAI-induced neuropathic pain rats. Bilateral sensorimotor and pain-related brain regions were mainly involved in this process. It indicated that modulation of brain metabolic connectivity might be an important mechanism of analgesic effect in EA stimulation for the treatment of neuropathic pain.

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.

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.

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

Facial synkinesis, a sequela of peripheral facial nerve palsy, is characterized by simultaneous involuntary facial movement during a voluntary desired one. Maladaptive cortical plasticity might be involved in the dysfunction of facial muscles. This cohort study investigated the cortical functional alterations in patients with unilateral facial synkinesis, using the task functional magnetic resonance imaging. Facial motor tasks, including blinking and smiling, were performed by 16 patients (aged 30.6 ± 4.5 years, 14 females/2 males) and 24 age- and sex-matched healthy controls (aged 29.1 ± 4.2 years, 19 females/5 males). Results demonstrated that activation in the cortico-facial motor representation area was lower during tasks in patients with facial synkinesis compared with healthy controls. Facial movements on either side performed by patients caused more intensive activation of the supplementary motor area on the contralateral side of the affected face, than those on the unaffected side. Our results revealed that there was cortical reorganization in the primary sensorimotor area and the supplementary motor area. This study was registered in Chinese Clinical Trial Registry (registration number: ChiCTR1800014630).

OBJECTIVEContralateral peripheral neurotization surgery has been successfully applied to rescue motor function of the hemiplegic upper extremity in patients with central neurological injury (CNI). It may contribute to strengthened neural pathways between the contralesional cortex and paretic limbs. However, the effect of this surgery in the lower extremities remains unknown. In the present study the authors explored the effectiveness and safety of contralateral peripheral neurotization in treating a hemiplegic lower extremity following CNI in adult rats.METHODSControlled cortical impact (CCI) was performed on the hindlimb motor cortex of 36 adult Sprague-Dawley rats to create severe unilateral traumatic brain injury models. These CCI rats were randomly divided into 3 groups. At 1 month post-CCI, the experimental group (Group 1, 12 rats) underwent contralateral L-6 to L-6 transfer, 1 control group (Group 2, 12 rats) underwent bilateral L-6 nerve transection, and another control group (Group 3, 12 rats) underwent an L-6 laminectomy without injuring the L-6 nerves. Bilateral L-6 nerve transection rats without CCI (Group 4, 12 rats) and naïve rats (Group 5, 12 rats) were used as 2 additional control groups. Beam and ladder rung walking tests and CatWalk gait analysis were performed in each rat at baseline and at 0.5, 1, 2, 4, 6, 8, and 10 months to detect the skilled walking functions and gait parameters of both hindlimbs. Histological and electromyography studies were used at the final followup to verify establishment of the traumatic brain injury model and regeneration of the L6-L6 neural pathway.RESULTSIn behavioral tests, comparable motor injury in the paretic hindlimbs was observed after CCI in Groups 1–3. Group 1 started to show significantly lower slip and error rates in the beam and ladder rung walking tests than Groups 2 and 3 at 6 months post-CCI (p < 0.05). In the CatWalk analysis, Group 1 also showed a higher mean intensity and swing speed after 8 months post-CCI and a longer stride length after 6 months post-CCI than Groups 2 and 3 (p < 0.05). Transection of L-6 resulted in transient skilled walking impairment in the intact hindlimbs in Groups 1 and 2 (compared with Group 3) and in the bilateral hindlimbs in Group 4 (compared with Group 5). All recovered to baseline level within 2 months. Histological study of the rat brains verified comparable injured volumes among Groups 1–3 at final examinations, and electromyography and toluidine blue staining indicated successful regeneration of the L6-L6 neural pathways in Group 1.CONCLUSIONSContralateral L-6 neurotization could be a promising and safe surgical approach for improving motor recovery of the hemiplegic hindlimb after unilateral CNI in adult rats. Further investigations are needed before extrapolating the present conclusions to humans.

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.

Central neurologic injury (CNI) causes dysfunctions not only in limbs but also in cognitive ability. We applied a novel peripheral nerve rewiring (PNR) surgical procedure to restore limb function. Here, we conducted a prospective study to develop estimates for the extent of preattentive processes to cognitive function changes in CNI patients after PNR. Auditory mismatch negativity (MMN) was measured in CNI patients who received the PNR surgery plus conventional rehabilitation treatment. During the 2-year follow-up, the MMN was enhanced with increased amplitude in the PNR plus rehabilitation group compared to the rehabilitation-only group as the experiment progressed, and progressive improvement in behavioural examination tests was also observed. Furthermore, we found a significant correlation between the changes in Fugl-Meyer assessment scale scores and in MMN amplitudes. These results suggested that PNR could affect the efficiency of pre-attention information processing synchronously with the recovery of motor function in the paralyzed arm of the in chronic CNI patients. Such electroencephalographic measures might provide a biological approach with which to distinguish patient subgroups after surgery, and the change in MMN may serve as an objective auxiliary index, indicating the degree of motor recovery and brain cognitive function.

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.

Electroacupuncture has been considered an effective neurorehabilitative approach to relieve neuropathic pain originating in the central nervous system. However, the neural mechanism underlying the effect of electroacupuncture on pain-relief remains largely unknown. The objective of this study was to investigate the alteration of hub configurations of brain networks caused by the sustained impact of electroacupuncture on a clinically relevant animal model of neuropathic pain. Rats were divided into four groups: normal, model, electroacupuncture, and sham-electroacupuncture. Rats of the last three groups received complete brachial plexus avulsion to evoke neuropathic pain. Electroacupuncture was conducted continuously for three months on the electroacupuncture group, while the sham intervention was performed on the sham-electroacupuncture group. Mechanical withdrawal thresholds were evaluated at the end of the first and third month of intervention. Graph theoretical network analysis compared the regional topological parameters and explored hub configurations of brain networks by longitudinal resting-state fMRI. Three-months electroacupuncture showed a significant pain-relief effect. Not the spatial distribution of hubs, but the hubness distribution showed a significant difference among groups after a three-month intervention. The proportion of more highly connected hub regions was significantly higher in the model rats than the normal rats, while that of the electroacupuncture group was considerably lower than the model group. Additionally, regional parameter changes showed a very similar distribution of hub proportions. It was concluded that long-term electroacupuncture might restore an adaptive equilibrium to a disrupted network and suppress maladaptive plastic changes that follow neuropathic pain. This may provide an important avenue for future strategies appropriate for therapeutic interventions.

Motor recovery of wrist and fingers is still a great challenge for chronic stroke survivors. The present study aimed to verify the efficiency of motor imagery based brain-computer interface (BCI) control of continuous passive motion (CPM) in the recovery of wrist extension due to stroke. An observational study was conducted in 26 chronic stroke patients, aged 49.0 ± 15.4 years, with upper extremity motor impairment. All patients showed no wrist extension recovery. A 24-channel highresolution electroencephalogram (EEG) system was used to acquire cortical signal while they were imagining extension of the affected wrist. Then, 20 sessions of BCI-driven CPM training were carried out for 6 weeks. Primary outcome was the increase of active range of motion (ROM) of the affected wrist from the baseline to final evaluation. Improvement of modified Barthel Index, EEG classification and motor imagery pattern of wrist extension were recorded as secondary outcomes. Twenty-one patients finally passed the EEG screening and completed all the BCI-driven CPM trainings. From baseline to the final evaluation, the increase of active ROM of the affected wrists was (24.05 ± 14.46)˚. The increase of modified Barthel Index was 3.10 ± 4.02 points. But no statistical difference was detected between the baseline and final evaluations (P > 0.05). Both EEG classification and motor imagery pattern improved. The present study demonstrated beneficial outcomes of MI-based BCI control of CPM training in motor recovery of wrist extension using motor imagery signal of brain in chronic stroke patients.

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.

Massage therapy is an alternative treatment for chronic pain that is potentially related to brain plasticity. However, the underlying mechanism remains unclear. We established a peripheral nerve injury model in rats by unilateral sciatic nerve transection and direct anastomosis. The experimental rats were treated over the gastrocnemius muscle of the affected hindlimb with a customized massage instrument (0.45 N, 120 times/min, 10 minutes daily, for 4 successive weeks). Resting-state functional magnetic resonance imaging revealed that compared with control rats, the amplitude of low-frequency fluctuations in the sensorimotor cortex contralateral to the affected limb was significantly lower after sciatic nerve transection. However, amplitudes were significantly higher in the massage group than in a sham-massage group. These findings suggest that massage therapy facilitated adaptive change in the somatosensory cortex that led to the recovery of peripheral nerve injury and repair. This study was approved by the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine of China (approval No. 201701001) on January 12, 2017.

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.

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.

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.

We assessed the diagnostic value of triple stimulation technique (TST) in eight patients with neurogenic thoracic outlet syndrome (TOS) by revealing the conduction block of the proximal lower trunk of the brachial plexus and locating the compression site.Eight patients fulfilling the conventional criteria of the lower-trunk neurogenic TOS were enrolled in our study. TST along with the central motor-conduction time was evaluated. The parameters including the TST amplitude ratio and the TST area ratio were compared between patients and controls.The amplitude ratio was significantly lower in the patient group than in the control group (patients: 0.518 ± 0.113; control: 0.954 ± 0.020, P0.01), so was the area ratio (patients: 0.453 ± 0.194; control group: 0.955 ± 0.192, P0.01). No significant difference of central motor-conduction time (CMCT) was seen between the patient group and the control group (patients: 6.62 ± 0.36 ms; control: 6.54 ± 0.36 ms; P=0.528). Surgical procedures proved the compression of the lower trunk in all patients.Our results indicated that there was conduction block besides axon loss in neurogenic TOS patients, and the conduction block was located between the nerve root emerging site and the supraclavicular stimulation site.We first applied TST in diagnosing neurogenic TOS, and we showed that the patient's TST ratio was significantly lower than normal. Combined with clinical manifestations, TOS can be more precisely diagnosed.

BACKGROUND Central neurological injury (CNI) is a major contributor to physical disability that affects both adults and children all over the world. The main sequelae of chronic stage CNI are spasticity, paresis of specific muscles, and poor selective motor control. Here, we apply the concept of contralateral peripheral neurotization in spasticity releasing and motor function restoration of the affected upper extremity. OBJECTIVE A clinical investigation was performed to verify the clinical efficacy of contralateral C7 neurotization for rescuing the affected upper extremity after CNI. METHODS In the present study, 6 adult hemiplegia patients received the nerve transfer surgery of contralateral C7 to C7 of the affected side. Another 6 patients with matched pathological and demographic status were assigned to the control group that received rehabilitation only. During the 2-year follow-up, muscle strength of bilateral upper extremities was assessed. The Modified Ashworth Scale and Fugl-Meyer Assessment Scale were used for evaluating spasticity and functional use of the affected upper extremity, respectively. RESULTS Both flexor spasticity release and motor functional improvements were observed in the affected upper extremity in all 6 patients who had surgery. The muscle strength of the extensor muscles and the motor control of the affected upper extremity improved significantly. There was no permanent loss of sensorimotor function of the unaffected upper extremity. CONCLUSION This contralateral C7 neurotization approach may open a door to promote functional recovery of upper extremity paralysis after CNI.

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.

Restoration of digital flexion after brachial plexus injury or forearm injury has been a great challenge for hand surgeons. Nerve transfer and forearm donor muscle transfer surgeries are not always feasible. The present study aimed at evaluating the effectiveness of restoring digital flexion by brachialis muscle transfer. Ten lower brachial plexus- or forearm-injured patients were enrolled. After at least 12 months following surgery, the middle-finger-to-palm distance was less than 2.5 cm in six patients. In the other four patients with less satisfactory results, secondary tenolysis surgery was performed and the middle-finger-to-palm distances were reduced to 2.0–4.0 cm. The average grasp strength was 20 ± 4 kg. Elbow flexion was not adversely affected. In conclusion, brachialis muscle transfer is an effective method for reconstructing digital flexion, not only in lower brachial plexus injury, but also in forearm injury patients. Level of evidence: IV

The treatment of brachial plexus avulsion injury remains a challenging problem. Admittedly, central nervous mechanisms play a significant role in the motor recovery of the paralyzed hand after peripheral nerve surgery. The present study aimed at investigating the relationship between cerebral reorganization and motor recovery after a unique peripheral crossing nerve transfer surgery in brachial plexus injury patients.In the present study, two brachial plexus avulsion injury patients with were followed up for 4 years after contralateral C7 nerve transfer surgery. In the surgery, an intact nerve root from the intact limb was transferred to repair the injured nerves. One patient showed a good motor recovery in the paralyzed hand while the other showed relatively poor outcomes. In the longitudinal follow-up, 9 PET scans of the brain were conducted in both patients at regular intervals of every 6 months. A correlation analysis between cerebral glucose metabolism and flexion power of the paralyzed wrists and fingers was performed to investigate the involvement of brain reorganization during the process of motor recovery.The cerebral glucose metabolism in the corpus callosum, premotor cortex (Broadmann Area 6) and the precuneus were found positively correlated with the motor recovery of the paralyzed hand in Patient A (P .01). Positive correlation between the cerebral glucose metabolism and the motor recovery of the paralyze hand was only present in the corpus callosum in Patient B (P .01).Corpus callosum, premotor cortex and precuneus were related with motor recovery after contralateral cervical nerve transfer surgery. The accumulating activation of these cortical regions potentially represented the recovery of high-order motor networks and may have facilitated the motor recovery.

Object Contralateral C-7 nerve transfer was developed for the treatment of patients with brachial plexus avulsion injury (BPAI). In the surgical procedure the affected recipient nerve is connected to the ipsilateral motor cortex, and the dramatic peripheral alteration may trigger extensive cortical reorganization. However, little is known about the long-term results after such specific nerve transfers. The purpose of this study was to investigate the long-term cortical adaptive plasticity after BPAI and contralateral C-7 nerve transfer. Methods In this study, 9 healthy male volunteers and 5 male patients who suffered from right-sided BPAI and had undergone contralateral C-7-transfer more than 5 years earlier were included. Functional MRI studies were used for the investigation of long-term cerebral plasticity. Results The neuroimaging results suggested that the ongoing cortical remodeling process after contralateral C-7 nerve transfer could last for a long period; at least for 5 years. The motor control of the reinnervated limb may finally transfer from the ipsilateral to the contralateral hemisphere exclusively, instead of the bilateral neural network activation. Conclusions The authors believe that the cortical remodeling may last for a long period after peripheral rearrangement and that the successful cortical transfer is the foundation of the independent motor recovery.

BACKGROUND Functional recovery after peripheral nerve injury and repair is related with cortical reorganization. However, the mechanism of innervating dual targets by 1 donor nerve is largely unknown. OBJECTIVE To investigate the cortical reorganization when the phrenic nerve simultaneously innervates the diaphragm and biceps. METHODS Total brachial plexus (C5-T1) injury rats were repaired by phrenic nerve-musculocutaneous nerve transfer with end-to-side (n = 15) or end-to-end (n = 15) neurorrhaphy. Brachial plexus avulsion (n = 5) and sham surgery (n = 5) rats were included for control. Behavioral observation, electromyography, and histologic studies were used for confirming peripheral nerve reinnervation. Cortical representations of the diaphragm and reinnervated biceps were studied by intracortical microstimulation techniques before and at months 0.5, 3, 5, 7, and 10 after surgery. RESULTS At month 0.5 after complete brachial plexus injury, the motor representation of the injured forelimb disappeared. The diaphragm representation was preserved in the "end-to-side" group but absent in the "end-to-end" group. Rhythmic contraction of biceps appeared in "end-to-end" and "end-to-side" groups, and the biceps representation reappeared in the original biceps and diaphragm areas at months 3 and 5. At month 10, it was completely located in the original biceps area in the "end-to-end" group. Part of the biceps representation remained in the original diaphragm area in the "end-to-side" group. Destroying the contralateral motor cortex did not eliminate respiration-related contraction of biceps. CONCLUSION The brain tends to resume biceps representation from the original diaphragm area to the original biceps area following phrenic nerve transfer. The original diaphragm area partly preserves reinnervated biceps representation after end-to-side transfer.

A 4-year-old girl who sustained the hemiplegic cerebral palsy and subsequent spasticity in the left upper extremity underwent the C7 nerve root rhizotomy and the contralateral C7 nerve root transfer to the ipsilateral middle trunk of brachial plexus through an interpositional sural nerve graft. In a 2-year follow-up, the results showed a reduction in spasticity and an improvement in extension power of the elbow, the wrist, and the second to fifth fingers. Scores from both Quality of Upper Extremity Skills Test and Modified Ashworth Scale tests had been significantly improved during follow-up. The outcomes from this case provided the evidence that combined the C7 nerve root rhizotomy and contralateral healthy C7 nerve root transfer to the ipsilateral middle trunk of brachial plexus not only partially released flexional spasticity but also strengthened extension power of the spastic upper extremity in children with the cerebral palsy.

Background The restoration of sensory and motor function in brachial plexus root avulsion patients is a difficult challenge. The central nervous system plays an important role in sensory recovery after peripheral nerve injury and repair. Objective To investigate the sensory restoration process after surgery at the cortical level in rodent models with a contralateral C7 nerve transfer. Methods Thirty-five male Sprague-Dawley rats were used in this experiment, and both behavioral tests and somatosensory evoked potentials were used to investigate the sensory function recovery of the injured forepaws and the cortical reorganization in the rats postoperatively. Results The results demonstrated a dynamic change in the ipsilateral somatosensory cortex, both in the shape and location, where overlapping sensory cortical representations of the healthy and injured forepaws were observed consistently. Behavioral tests show that the sensation first occurred only in the healthy forepaw and later in both when stimulating the injured one, which suggested a tendency of the sensation function to recover in the injured forepaws of the rats as time progressed. Conclusion The cortical reorganization occurred only in the ipsilateral hemisphere, which is different from the motor cortex reorganization using the same model as that described in a previous study. This reorganization pattern offers an interpretation of the unique sensory recovery process after the transfer of the C7 nerve to the contralateral median nerve, but also provides the basis for further sensory restoration in clinical practice.

The purpose of our study was to establish the profile of cortical reorganization in whole BPAI on rats and evaluate changes of cortical reorganization after repair of the median nerve with the contralateral C7 root transfer. Forty adult SD rats underwent whole roots avulsion of left brachial plexus, among them 20 received contralateral C7 root transfer to the injured median nerve. Intracortical microstimulation was performed in primary motor cortex (M1) at intervals of 3, 5, 7, and 10 months, postoperatively. The maps of motor cortical responses were constructed. Five normal rats were used as the control. Results showed that stimulating right M1 elicited motion of left vibrissae, submaxilla, neck, back, and left hindlimb after left BPAI, among them neck representation area replaced the forelimb area throughout the reorganization process. The left forelimb representation area was found in the left motor cortex 5 months after the contralateral C7 root transfer and existed in both motor cortexes at 7th postoperative month. The left forelimb representation area was detected only in right motor cortex at 10th month, postoperatively. In conclusions, after the contralateral C7 root transfer for repair of the median nerve in BPAI, the cortical reorganization occurred in a time-dependent reorganization. The findings from this study demonstrate that brain involves in the functional recovery after BPAI and repair with nerve transfer and suggest that efforts to improve the results from nerve repair should address the peripheral nerve as well as the brain.

There have been controversies on the contribution of contralesional hemispheric compensation to functional recovery of the upper extremity after a unilateral brain lesion. Some studies have demonstrated that contralesional hemispheric compensation may be an important recovery mechanism. However, in many cases where the hemispheric lesion is large, this form of compensation is relatively limited, potentially due to insufficient connections from the contralesional hemisphere to the paralyzed side. Here, we used a new procedure to increase the effect of contralesional hemispheric compensation by surgically crossing a peripheral nerve at the neck in rats, which may provide a substantial increase in connections between the contralesional hemisphere and the paralyzed limb. This surgical procedure, named cross-neck C7-C7 nerve transfer, involves cutting the C7 nerve on the healthy side and transferring it to the C7 nerve on the paretic side. Intracortical microstimulation, Micro-PET and histological analysis were employed to explore the cortical changes in contralesional hemisphere and to reveal its correlation with behavioral recovery. These results showed that the contralesional hemispheric compensation was markedly strengthened and significantly related to behavioral improvements. The findings also revealed a feasible and effective way to maximize the potential of one hemisphere in controlling both limbs.

We demonstrate a high efficiency top-emitting polymer light-emitting diode (TPLED) with chromium (Cr) taking as the anode. The TPLED structure is Cr/poly-3, 4-ethylenedioxythiophene (PEDOT:PSS)/poly [2-(4-3',7'-dimethyloctyloxy)-phenyl]-p-phenylenevinylene) (P-PPV)/Ba/Ag. The Cr (100 nm) anode is prepared by sputter-depositing in a vacuum chamber. It is found that the device emissive properties are affected dramatically by the thickness of both PEDOT:PSS and the Ag cathode. Optimized thicknesses of PEDOT:PSS and Ag layer are 60 nm and 15 nm, respectively. The diode exhibits excellent electroluminescence (EL) properties, such as a turn-on voltage of 3.32 V, luminous efficiency of 4.41 cd/A and luminance of 6989 cd/m2 at driving voltage of about 9 V.

Saturated red polymer light-emitting diodes have been fabricated with a single emitting polymer blend layer of poly[2-(2-ethylhexyloxy)-5-methoxy-1,4-phenylenevinylene] (MEH-PPV) and poly[9,9-dioctylfluorene-co-4,7-di-2-thienyl-2,1,3-benzothiadiazole] (PFO-DBT15). Saturated red emission with the Commission Internationale de l’Eclairage (CIE) coordinates of (0.67, 0.33) was obtained. The device stability was investigated. The results showed that energy transfer occurred from MEH-PPV to PFO-DBT15, and MEH-PPV improved the hole injection and transportation.

Background Brachial plexus injury (BPI) is a serious peripheral nerve injury, and clinical outcomes are generally unsatisfactory. It has been reported that cortical plasticity could influence the restoration of motor function. However, the neurologic mechanism of BPI is unclear, which provides a basis for further investigation. The supplementary motor area (SMA) plays an important role in the regulation of motor function. This study aims to explore SMA–whole brain functional connectivity after deafferentation of the brachial plexus. Methods Study subjects included 16 patients with BPI and 8 healthy volunteers. The seed region was defined by a block-design functional magnetic resonance imaging program that used unilateral imaginary hand grasp motion as a task stimulus. Next, the voxel–wise functional connectivity between the predefined region and the other regions of the brain was calculated. Results We discovered decreased voxel–wise functional connectivity between the SMA and multiple brain regions, including precuneus, posterior cingulum cortex, and anterior cingulum cortex, that are closely associated with information integration or motor processing in patients with BPI. Conclusions Patients with BPI showed weakened functional connectivity between hand grasp–related areas and the SMA and multiple regions associated with motor processing or information integration. A clear image of the functional status of the brain after deafferentation was provided. On the basis of this discovery, a relationship between changes in neuroimaging measurements and clinical outcomes can be determined in future studies.

Background: Deafferentation pain secondary to brachial plexus avulsion, spinal cord injury, and other peripheral nerve injuries is often refractory to conventional treatments. Stimulation of the primary motor cortex (M1) has been proven to be an effective treatment for intractable deafferentation pain. The mechanisms underlying the attenuation of deafferentation pain by motor cortex stimulation remain hypothetical. Objectives: The purpose of this case report is to: (1) summarize a case in which a patient suffering chronic intractable deafferentation pain for 25 years underwent rTMS treatment over M1, (2) describe the evidence from PET imaging, and (3) reveal a possible relief mechanism with cortical plasticity. Study design: Case report. Setting: University hospital. Results: This patient had successful pain control with no transient or lasting side effects. The pain relief remained stable for at least one week. At the end of the 20-day procedure, pain relief was obtained according to the Visual Analog Scale (VAS) (-34.6%) and the McGill Pain Questionnaire (MPQ) (-31.6%). In the PET/CT scans, the glucose metabolism was significantly reduced contralaterally to the pain side in the anterior cingulate cortex (ACC), insula, and caudate nucleus. There was no statistically significant difference in any other cortical area. Limitations: Single case of a patient with long-term intractable deafferentation pain having a PET study. Conclusion: This study implies that a single session of 20 Hz rTMS over the motor cortex could reduce the pain level in patients suffering from long-term, intractable deafferentation pain. The stimulation of the M1 induces deactivation in the ACC, insula, and caudate nucleus. The changes in these pain-related regions may mirror an adaptive mechanism to pain relief after rTMS treatment. Key words: Neuropathic pain management, deafferentation pain, transcranial magnetic stimulation, motor cortex stimulation, cortical plasticity, positron emission tomography

Object: Contralateral C-7 nerve transfer was developed for the treatment of patients with brachial plexus avulsion injury (BPAI). In the surgical procedure, the affected recipient nerve is connected to the ipsilateral motor cortex, and the dramatic peripheral alteration may trigger extensive cortical reorganization. However, little is known about the long-term results after such specific nerve transfers. The purpose of this study was to investigate the long-term cortical adaptive plasticity after BPAI and contralateral C-7 nerve transfer. Methods: In this study, 9 healthy male volunteers and 5 male patients who suffered from right-sided BPAI and had undergone contralateral C-7-transfer more than 5 years earlier were included. Functional magnetic resonance imaging studies were used for the investigation of long-term cerebral plasticity. Results: The neuroimaging results suggested that the ongoing cortical remodeling process after contralateral C-7 nerve transfer could last for a long period, at least for 5 years. The motor control of the reinnervated limb may finally transfer from the ipsilateral to the contralateral hemisphere exclusively, instead of the bilateral neural network activation. Conclusions: The authors believe that the cortical remodeling may last for a long period after peripheral rearrangement and that the successful cortical transfer is the foundation of the independent motor recovery.

Department of Hand Surgery, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China Department of Radiology, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China PET Center, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China State Key Laboratory of Medical Neuroscience, Fudan University, 138, Yi Xue Road, Shanghai 200032, China

In this paper, the two-dimensional hole gas (2DHG) induced in the heterojunction were investigated in detail. The density of the 2DHG was calculated at first, then, based on the semiconductor-insulator-semiconductor and superlattice critical thickness model and using the self consistent Poisson-Schrdinger calculations, the influence of the AlGaN barrier and the top GaN layer thickness on the distribution of the 2DHG were calculated when the barrier layer is fully strained and half strained. The Schottky device with this structure was fabricated and C-V measurement was made to verify the existence of the 2DHG and the validity of calculation results. Finally, the 2DHG effects on p-GaN/AlGaN/GaN Schottky photodetector were investigated. Due to the polarization and Stark effect, the spectral responses with the 10nm blue shift are observed. Under zero bias, the peak responsivity of the device is about 0.022A/W, and increases to 0.19A/W under 1V reverse bias, which approaches the theoretical limit.