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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.

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.

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

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. 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.

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.

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.

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.

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.