Abstract

Introduction The amputation of a hand is followed by a cascade of plastic changes into the motor and somatosensory pathways in the CNS; such changes are probably contributing to the Phantom limb syndrome (PLS), a distressing situation affecting the majority of amputees, and could be modulated providing sensory input to the stump or amputation zone. Very few information is reported in literature explaining how plastic changes evolve during the use of prosthesis, particularly the new sensorized hand prosthesis, which provide the use of intraneural electrodes able to restore a “natural” somatosensory feedback. In this line, we performed a clinical study with four trans-radial amputees, who received an implant of four transversal intrafascicular electrodes in median and ulnar nerves controlling hand prosthesis, with the aim to investigate cortical changes occurring during trainings of different durations (4–24 weeks). Methods All patients underwent to a multimodal evaluation performed before and after the use of neural-interfaced hand prosthesis, including TMS examination with motor maps production, SEPs recording, EEG source analysis, connectivity analysis and fMRI. Standard pain questionnaires (VAS, McGill and PPI scores) were used to assess the course of PLS. Results After the interventions, the following findings were observed: – TMS motor maps showed a reduction and a partial reversal of an initial inter-hemispheric asymmetry (because of an enlargement of the excitable area on the hemisphere contralateral to the stump); – SEPs based on N20 component showed a modification of the cortical topography in the central-parietal areas contralateral to the amputation site; – EEG source analysis showed a widespread reduction of delta activity and a significant increase of alpha activity in the central-parietal areas in both hemispheres; – According to the graph theory, the analysis of the sensory-motor network showed in both hemispheres a significant increase of the Characteristic Path Length and a significant decrease of Small World Index in the alpha band; – fMRI showed a decrease in activation of supplementary and premotor areas with a prominent and more selective activation of the M1 area; – All the patients experiencend a decrease of PLP. Conclusion Our data provides a direct and unique evidence of brain plastic changes following the restoration of somatosensory feedback from a missing limb. We observed changes in the cortical organization towards a more physiological state in all the four patients during an extensive use of robotic hand. We associated these brain reactions to a decrease in pain intensity and an improvement of prosthesis control performance. The prosthetic system could induce reduction in aberrant plasticity and promote ‘good’ “training-induced” plasticity. Neurophysiological and neuroimaging analysis could be seen as potential biomarker of the level of CNS reorganization and therefore used as parameter of the effectiveness achieved by the prosthetic device and its interfaces.

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