| Previous researches have discovered that amputation would result in change of behavior pattern and entrance block of sensorimotor information,which might further lead to structural and functional reorganization of the nervous system.The patients may also experience phantom limb pain?PLP?after amputation.PLP refers to a pathological phenomenon characterized by the subjective feeling of the patient that the amputated limbs still exist,associated with pains of different degrees and natures.PLP is the most common complication of amputation,and has been drawing extensive attention due to its high incidence rate,difficulty in curing and significant impact on the physical and psychological health of the patient.PLP patients experience cognitive changes in various dimensions including pain and emotion,and would possibly result in more complicated brain reorganization patterns.The brain pathophysiological mechanism was still unclear and further studies were required.In recent years,with rapid development and extensive application of MRI and brain imaging analysis approaches,new approaches have been provided for studying the structural and functional reorganization patterns of brain of amputees and PLP patients.Different MRI techniques had their unique strong points and advantages in terms of identifying the brain structure and function.As such,it was of great significance to discuss the pathological mechanism by combining the image features obtained with different imaging techniques.The structural MRI,diffusion tensor imaging?DTI?and resting-state fMRI were used to study the structural and functional reorganization of the brain of lower limb amputees?LLA?.In addition,a number of brain network analyzing approaches were used to analyze of brain reorganization the PLP patient,and carry out multi-level in-depth study of the neuropathological mechanism of PLP from the perspective of brain network.1?The voxel-based morphometry?VBM?and cortical thickness analyzing method was used to study the role of two implicit factors,amputation and PLP,in structural reorganization of brain gray matter of the amputees.The research findings indicated that compared with the healthy control?HC?,the LLA exhibited thinning bilateral precentral gyrus.Furthermore,the grey matter volume in the contralateral?contralateral to the side of amputation?basal ganglia and bilateral thalamus reduced significantly.Such results suggested anaplasia of bilateral sensorimotor loop of the amputees as a result of reduction of sensorimotor input after amputation.Compared with the amputees without PLP,PLP patients exhibited structural changes in the pain related brain regions,including reduction of grey matter volume in the cerebellum,as well as ipsilateral?ipsilateral to the side of amputation?inferior parietal lobule and thinning of the contralateral insula.In addition,the reduced volume of cerebellum was significantly negatively related to the VAS of the PLP patients.Such results suggested structural reorganization of brain regions related to pain processing after amputation,which was reflected by the atrophy of cerebral cortex.This would further result in regulation disorder of pain network and would possibly be the key factor leading to occurrence of PLP.2.A combination of DTI and resting-state fMRI was used to study the brain structure and function of amputees and PLP patients.Tract-based spatial statistics?TBSS?results indicated that a consistent significant decreased FA value and significant increased MD value were observed in the contralateral corpus callosum,anterior thalamic radiations and corticospinal tract in the LLA.The network-based statistics?NBS?results showed significant decrease structural connectivity in the two network components,one was mainly involved in the parietal cortex and pallidum.The decrease of structural connectivity in this critical loop indicated the decreased sensorimotor information transmission ability of the amputees;the other component was a sub-network with the amygdala as the connection center.Any abnormality of this network suggested changes of the emotional status of amputees.Further analysis based on graph theory revealed that both the structural and functional network of the LLA and HC exhibited small-world attribute.However,compared with HC,the LLA exhibited reduced ability of global network information transmission,which was reflected by significant increase of characteristic path length.On the node level,the structural network of the LLA mainly exhibited decreased nodal centrality in the contralateral sensorimotor regions,such as postcentral gyrus,putamen and pallidum.In addition,proprioception related brain regions were also involved,such as the precuneus and posterior cingulum gyrus.Such results suggested that the brain reorganization process after amputation did not only implicate sensorimotor network?SMN?,but also damaged the brain regions responsible for ontology-based information processing.The brain functional network exhibited decreased nodal centrality in SMA.In addition,change of nodal centrality related to ontology-based information processing ability,including posterior cingulum gyrus and middle cingulum gyrus,was observed.Compared with the LLA without PLP,PLP patients mainly exhibited abnormality of nodal centrality in structural and functional networks,in particular the brain regions related to processing of pain related emotive information,such as orbitofrontal cortex,anterior cingulum gyrus and amygdala.Such change of information transmission ability of the brain area might play an important role in pathological pain emotion perception of PLP patients.3.To further discuss the reorganization of the SMN of LLA,we used two functional connectivity?FC?methods to study this system.The ROI-wise connectivity analysis results indicated that compared with HC,the LLA mainly exhibited decreased FC between the subcortical nuclei and the contralateral S1M1.The seed-based whole-brain FC analysis revealed that brain regions with decreased FC with the contralateral S1M1 extended beyond the SMN to the prefrontal and visual cortices.Further correlation analysis showed that decreased FC between the subcortical and the cortical regions in the sensorimotor network would experience progressive increase with time after amputation.Such results suggested an extensive reorganization pattern on the network level in the brain after amputation.Particularly,the change of subcortex and cortex FC of the SMN could be used as a new image indicator to predict the motor function recovery of amputees.4.The independent component analysis?ICA?was used to detect the change of FC within and between resting-state networks?RSNs?in the PLP patients.We identified 12 RSNs using the group ICA method.The findings indicated that compared with HC,PLP patients exhibited abnormality of FC in a number of RSNs,including the SMN,default mode network?DMN?,basal ganglia network and insula-operculum network.Specifically,the inferior parietal lobule connectivity in the DMN was significantly positively correlated with the VAS,and the postcentral gyrus connectivity in the SMN was also in a significant positive correlation with the time since amputation.Such research findings suggested that long-term sensory information entrance block and pain would possibly disturb the organizational mode of normal RSNs,resulting in abnormality in pain sensory discrimination,pain perception,relieving and inhibiting functions of pain,Furthermore,the increased FC between the dorsal attentional network and posterior DMN of PLP patients and decreased FC between the anterior DMN,posterior DMN and basal ganglia network suggested that excessive attention to pain would damage the connection pattern of DMN and functional output and influence the external locomotor performance.At the same time,there was significant increase of FC between the execution control network,left frontoparietal network and medial visual network of PLP patients.Such an increase of FC of the visual information perception-information transmission-information regulation loop might be a compensation effect of the sensorimotor and visual perception efficiency of amputees.The findings provided a new train of thought for studying the impact of missing sensorimotor information and pain on the visual-motor and cognitive function of brain spontaneous network in PLP patients.5.A combination of two brain network analyzing methods,functional connectivity density?FCD?and seed-based whole-brain FC,was used to study the abnormality of FC of brain regions related to pain in PLP patients.The results indicated that compared with the HC,PLP patients exhibited decrease of short-range FCD in the contralateral parahippocampal gyrus and insula,and bilateral precentral gyri,as well as increase of short-range FCD in contralateral middle occipital gyrus.In addition,the PLP patients also exhibited abnormality of long-distance information transmission ability,and significant increase of long-range FCD in the contralateral cerebellum and middle occipital gyrus and ipsilateral middle occipital gyrus and superior temporal gyrus,as well as significant decrease of long-range FCD in the ipsilateral precuneus.The correlation analysis results indicated that in PLP patients,the FCD of precuneus,precentral gyrus,insula and middle occipital gyrus was significantly correlated with the VAS.Further seed-based whole-brain FC suggested that PLP patients experienced extensive FC changes in the pain related brain regions,reflected by the reduction of information transmission ability in the RSNs represented by the seed.However,it should be noted that FC between those pain related brain regions and the dorsolateral prefrontal cortex?DLPFC?exhibited consistent increase.The brain region was able to regulate the functions of other pain loops based on their own activation level.This suggested that we could apply therapies,such as repetitive transcranial magnetic stimulation?rTMS?,to effectively regulate the activity of DLPFC,so as to mitigate the phantom limb pain.6.We construct the rich club organization of structural and functional network,and probe into the change of structural connectivity,FC and network attributes of rich club organization in PLP patients.The results indicated that rich club organizations were observed in both groups of subjects.The rich club nodes included prefrontal cortex,cingulum gyri,precuneus and occipital lobe,with significant overlapping with key brain regions of SMN,DMN and visual network.Compared with HC,PLP patients only exhibited decrease of structural and functional connectivity and global network efficiency in the rich club organization.No change was observed outside the rich club organization.The results suggested that the change of information transmission pattern of PLP patients was specific,and was mainly observed in this key network.More importantly,we found that the decrease of structural and functional connectivity of rich club organization was in a significant negative correlation with the course of disease.In another word,the longer the course of disease was,the lower the connectivity strength of rich club organization of PLP patients would be.This indicated the close relation between the abnormal functional output of PLP patients and progressive disorder of rich club organization.Such research findings highlighted the important role of rich club organization in brain reorganization and neuropathological mechanism of PLP patients.7.Mirror therapy was deemed as being able to reverse the brain non-adaptive functional reorganization of PLP patients,thus mitigating the pain of patients.However,how the mirror movement played a role in the brain and the mechanism of its action on the brain were still unclear.In this research,the functional near infrared spectroscopy?fNIRS?was used to test the activation pattern of the brain of healthy subjects with motor execution and mirror movement,and further discuss the characteristics of change of oxyhemoglobin?HbO2?,as part of the preliminary study on mechanism of action of mirror movement in the brain.The findings indicated that the bilateral sensorimotor cortexes of the brain were significantly activated in each of the movement tasks,with the right side of the brain exhibiting stronger activity.For mirror movement,the contralateral?right side?cerebral hemisphere of mirror movement limb had smaller activation scope and lower intensity;however,there was no significant between-group difference with the motor execution.Such results suggested that the mirror movement of the right foot was able to realize motor execution function of left foot,so as to activate the sensorimotor loop of the contralateral cerebral hemisphere.Furthermore,we also found the variation trend of relative concentration of HbO2 in the performance of the two tasks was to some extent consistent.What?s interesting was that given the motor simulation of the same time,the duration of stimulating effect of mirror movement on brain was shorter than that of motor execution.It suggested that in the process of mirror movement,attention should be paid to the impact of duration of stimulation on brain activation effect.Our research results acknowledged the effect of mirror movement limb in the mirror movement on the sensorimotor loop of the contralateral cerebral hemisphere from the perspective of imageology,which provides a basis for the clinical application of mirror therapy. |
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