Neuroprosthetics research in amputee patients aims at developing new prostheses that move and feel like real limbs. Targeted muscle and sensory reinnervation (TMSR) is such an approach and consists of rerouting motor and sensory nerves from the residual limb towards intact muscles and skin regions. Movement of the myoelectric prosthesis is enabled via decoded electromyography activity from reinnervated muscles and touch sensation on the missing limb is enabled by stimulation of the reinnervated skin areas. Here we ask whether and how motor control and redirected somatosensory stimulation provided via TMSR affected the maps of the upper limb in primary motor (M1) and primary somatosensory (S1) cortex, as well as their functional connections. To this aim, we tested three TMSR patients and investigated the extent, strength, and topographical organization of the missing limb and several control body regions in M1 and S1 at ultra high-field (7 T) functional magnetic resonance imaging. Additionally, we analysed the functional connectivity between M1 and S1 and of both these regions with fronto-parietal regions, known to be important for multisensory upper limb processing. These data were compared with those of control amputee patients (n = 6) and healthy controls (n = 12). We found that M1 maps of the amputated limb in TMSR patients were similar in terms of extent, strength, and topography to healthy controls and different from non-TMSR patients. S1 maps of TMSR patients were also more similar to normal conditions in terms of topographical organization and extent, as compared to non-targeted muscle and sensory reinnervation patients, but weaker in activation strength compared to healthy controls. Functional connectivity in TMSR patients between upper limb maps in M1 and S1 was comparable with healthy controls, while being reduced in non-TMSR patients. However, connectivity was reduced between S1 and fronto-parietal regions, in both the TMSR and non-TMSR patients with respect to healthy controls. This was associated with the absence of a well-established multisensory effect (visual enhancement of touch) in TMSR patients. Collectively, these results show how M1 and S1 process signals related to movement and touch are enabled by targeted muscle and sensory reinnervation. Moreover, they suggest that TMSR may counteract maladaptive cortical plasticity typically found after limb loss, in M1, partially in S1, and in their mutual connectivity. The lack of multisensory interaction in the present data suggests that further engineering advances are necessary (e.g. the integration of somatosensory feedback into current prostheses) to enable prostheses that move and feel as real limbs.

中文翻译：

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有针对性的肌肉和感觉神经支配的截肢者的上肢皮质图

在截肢患者中进行神经假体研究的目的是开发能够移动并感觉像真实肢体的新假体。有针对性的肌肉和感觉神经支配（TMSR）是一种这样的方法，包括将运动神经和感觉神经从残肢转移到完整的肌肉和皮肤区域。肌电假体的运动是通过神经支配的肌肉的解码肌电图活动来实现的，而缺损肢体的触觉则可以通过神经支配的皮肤区域的刺激来实现。在这里，我们询问通过TMSR提供的运动控制和重定向体感刺激是否以及如何影响初级运动（M1）和初级体感（S1）皮质的上肢图以及它们的功能连接。为此，我们测试了三名TMSR患者，并调查了其程度，强度，超高场（7 T）功能磁共振成像中M1和S1中缺失肢体和几个控制体区域的组织和地形组织。此外，我们分析了M1和S1之间以及这两个区域与额顶区域的功能连接性，这对于多感觉上肢处理很重要。将这些数据与对照截肢患者的数据进行比较（n = 6）和健康对照（n= 12）。我们发现，TMSR患者截肢的M1图在范围，强度和地形方面与健康对照者相似，并且与非TMSR患者不同。与非目标肌肉和感觉神经支配患者相比，TMSR患者的S1图在地形组织和程度方面也与正常情况更为相似，但与健康对照组相比，其激活强度较弱。M1和S1上肢图谱在TMSR患者中的功能连通性与健康对照组相当，而在非TMSR患者中则有所降低。但是，就健康对照组而言，TMSR和非TMSR患者的S1和额顶区域之间的连通性均降低。这与在TMSR患者中缺乏完善的多感官作用（触摸的视觉增强）有关。总的来说，这些结果表明，有针对性的肌肉和感觉神经支配如何使M1和S1处理与运动和触摸相关的信号。此外，他们认为TMSR可以抵消肢体丧失后通常在M1，部分在S1及其相互连接中发现的适应不良的皮质可塑性。当前数据缺乏多感觉交互作用，这表明进一步的工程进展是必要的（例如将体感反馈整合到当前的假体中），以使假体能够像真实的肢体一样运动和感觉。此外，他们认为TMSR可以抵消肢体丧失后通常在M1，部分在S1及其相互连接中发现的适应不良的皮质可塑性。当前数据缺乏多感觉交互作用，这表明进一步的工程进展是必要的（例如将体感反馈整合到当前的假体中），以使假体能够像真实的肢体一样运动和感觉。此外，他们认为TMSR可以抵消肢体丧失后通常在M1，部分在S1及其相互连接中发现的适应不良的皮质可塑性。当前数据缺乏多感觉交互作用，这表明进一步的工程进展是必要的（例如将体感反馈整合到当前的假体中），以使假体能够像真实的肢体一样运动和感觉。