Neuroimaging Studies On Brain Reorganization In Upper-Limb Amputees

Amputees lost the sensory and motor function of the corresponding extremity,meanwhile,a lot of adaptive and maladaptive changes happen in the brain.The amputation could lead to abnormal sensations,such as phantom limb pain,phantom limb sensation,residual limb pain and residual limb sensation.Studies on the brain reorganization would help to understand the mechanisms underlying abnormal sensations,and facilitate the development of new rehabilitation methods,which has great potential of clinical applications.We studied the brain reorganization in structure,resting-state function and motor imagery.By using magnetic resonance imaging(MRI),we collected the T1 weighted image and resting-state functional MRI data from right upper-limb amputees and agematched controls.The structural reorganization was studied using surface-based morphological method and the functional reorganization using amplitude of low frequency fluctuation(ALFF)and functional connectivity(FC).Meanwhile,using mental rotation task,we collected both behavioral and electroencephalography(EEG)data.The brain activity of amputees during motor imagery with healthy controls were compared in aspects of event related potential(ERP)and event related desynchronization(ERD).Taking the behavioral performance and clinical ratings together,we studied brain reorganization comprehensively.The major results and conclusions of the dissertation are summarized as follows.The structural results showed that amputation was associated with reduced gray matter volume in left putamen and thalamus.Amputees also exhibited reduced white matter(WM)volume in the central part of corpus callosum and their WM volumes were negatively correlated with the time since amputation.In the cortical level,we found gray matter atrophy in left precentral gyrus,right insular,bilateral prefrontal cortex and bilateral occipital cortex.These structural changes along the sensory and motor pathways and association cortex might be related to the pain experience and adaptive alteration in the visual pathway.The resting-state blood oxygenation level dependent funtional MRI data showed that,compared with controls,amputees had a larger fractional ALFF(fALFF)in left postcentral gyrus,and an increased FC value between left postcentral gyrus and left lateral occipito-temporal gyrus,which was positively correlated with the time since amputation as well as the intensity of residual limb pain.In contrast,the amputees exhibited a decreased fALFF in left precuneus,as well as a decrease of FC between left precuneus and right anterior transverse collateral sulcus.Our results also showed a larger fALFF in left calcarine sulcus in amputees,and an increase of FC between left calcarine sulcus and the right lingual gyrus,which was positively correlated with the intensity of phantom limb sensation.These reorganizations in multiple cortical regions in amputees showed the increased association between sensorimotor area and the visual representation area of body,the decreased activity in default mode network,and the increased connectivity inside the visual area related to phantom limb sensation.Using the motor imagery task,we found the amputees responded slower than the controls.In the early visual processing phase,amputees and controls showed a similar P100.During the categorization phase,the amputees exhibited a decreased N200 compared with controls,which was positively correlated with the time since amputation.In the mental rotation phase,controls had a larger ERP for the right upright hand than that for the left upright hand,while amputees had a larger ERP for the left(intact)upright hand than that for the right(affected)upright hand.Moreover,compared with the controls,significantly prolonged response time for both the intact and missing hands were observed specifically in amputees who perceived a phantom limb during the task but not in those without phantom limb perception.Event-related desynchronization of EEG in the β band(β-ERD)in central and parietal areas showed an angular disparity specifically in amputees with phantom limb perception,with its source localized in the right inferior parietal lobule.The response time as well as the β-ERD values were significantly positively correlated with phantom vividness.Thus,early visual processing was not affected by limb amputation.However,the perceptual salience of hand pictures decreased,and the handedness changed in the amputees.Our results also suggest that phantom limb perception during the task is an important interferential factor for motor imagery,which might be related to a change of the body representation due to the unnatural posture of the phantom limb.In summary,by using EEG and MRI,we investigate structural and resting-state functional reorganization of right upper limb amputee,as well as the brain activity during motor imagery.We found that phantom limb sensation interfered with motor imagery and had an impact on the functional reorganization in visual cortex.The reorganization in the visual cortex showed a complex pattern as the gray matter atrophied,the spontaneous activity increased and the process of early visual encoding remains intact.We also found time-related reorganizations,for example,the atrophy of white matter in the central part of corpus callosum,increased functional connectivity between motor area and visual area in the affected hemisphere,and the decreased amplitude of N200 component.Such a long-term reorganization may indicate the formation of new connections in the brain.Our study enriches the current understanding of the neural substrate of brain reorganization in amputees.