Kishore Asha, Meunier Sabine, Popa Traian
Department of Neurology, Comprehensive Care Centre for Movement Disorders, Sree Chitra Tirunal Institute for Medical Sciences and Technology , Kerala , India.
Institut du Cerveau et de la Moelle epiniere (ICM), INSERM U1127, CNRS UMR 7225, Université Pierre et Marie Curie-Paris 6 UMR S975 , Paris , France ; Centre de Neuroimagerie de Recherche (CENIR), l'Institut du Cerveau et de la Moelle epiniere (ICM) , Paris , France.
Front Neurol. 2014 May 6;5:68. doi: 10.3389/fneur.2014.00068. eCollection 2014.
Normal motor behavior involves the creation of appropriate activity patterns across motor networks, enabling firing synchrony, synaptic integration, and normal functioning of these networks. Strong topography-specific connections among the basal ganglia, cerebellum, and their projections to overlapping areas in the motor cortices suggest that these networks could influence each other's plastic responses and functions. The defective striatal signaling in Parkinson's disease (PD) could therefore lead to abnormal oscillatory activity and aberrant plasticity at multiple levels within the interlinked motor networks. Normal striatal dopaminergic signaling and cerebellar sensory processing functions influence the scaling and topographic specificity of M1 plasticity. Both these functions are abnormal in PD and appear to contribute to the abnormal M1 plasticity. Defective motor map plasticity and topographic specificity within M1 could lead to incorrect muscle synergies, which could manifest as abnormal or undesired movements, and as abnormal motor learning in PD. We propose that the loss of M1 plasticity in PD reflects a loss of co-ordination among the basal ganglia, cerebellar, and cortical inputs which translates to an abnormal plasticity of motor maps within M1 and eventually to some of the motor signs of PD. The initial benefits of dopamine replacement therapy on M1 plasticity and motor signs are lost during the progressive course of disease. Levodopa-induced dyskinesias in patients with advanced PD is linked to a loss of M1 sensorimotor plasticity and the attenuation of dyskinesias by cerebellar inhibitory stimulation is associated with restoration of M1 plasticity. Complimentary interventions should target reestablishing physiological communication between the striatal and cerebellar circuits, and within striato-cerebellar loop. This may facilitate correct motor synergies and reduce abnormal movements in PD.
正常的运动行为涉及在运动网络中创建适当的活动模式，从而实现放电同步、突触整合以及这些网络的正常功能。基底神经节、小脑及其向运动皮层重叠区域的投射之间存在强烈的地形特异性连接，这表明这些网络可能会相互影响彼此的可塑性反应和功能。因此，帕金森病（PD）中纹状体信号传导缺陷可能导致相互连接的运动网络内多个层面出现异常振荡活动和异常可塑性。正常的纹状体多巴胺能信号传导和小脑感觉处理功能会影响M1可塑性的缩放和地形特异性。在PD中，这两种功能均异常，似乎导致了M1可塑性异常。M1内运动图谱可塑性和地形特异性缺陷可能导致肌肉协同作用错误，这可能表现为异常或不期望的运动，以及PD中的异常运动学习。我们提出，PD中M1可塑性的丧失反映了基底神经节、小脑和皮质输入之间协调的丧失，这转化为M1内运动图谱的异常可塑性，并最终导致PD的一些运动症状。在疾病进展过程中，多巴胺替代疗法对M1可塑性和运动症状的初始益处会丧失。晚期PD患者左旋多巴诱发的运动障碍与M1感觉运动可塑性丧失有关，小脑抑制性刺激减轻运动障碍与M1可塑性恢复有关。补充干预措施应旨在重新建立纹状体和小脑回路之间以及纹状体 - 小脑环路内的生理通信。这可能有助于实现正确的运动协同作用，并减少PD中的异常运动。
