## 5 Discussion
Interestingly, significant differences were found pre-post intervention for both the trained limb and control limb for figural error, maximum isometric wrist strength and submaximal grip force endurance. This could partly be attributed to a neurophysiological concept known as cross-education, where one limb is trained, and the control or untrained limb also shows improvements in strength measures following unilateral resistance training [22]. While not a facet of the study hypotheses, this finding generates interesting research questions. A systematic review demonstrated an overall 17% increase in strength for the untrained limb and a 30% increase in strength for the trained limb following ipsilateral strength training [27]. After a 5-week maximal wrist extension intervention in stroke recovery, a 42% increase in extension strength was found in the trained arm and a 35% increase in the control arm [28]. Although literature on cross-education in an MS population is lacking, it is known that MS affects the CNS, causing damage to structure and function via afferent and efferent pathways and rehabilitation of one limb helps overall CNS conduction [6]. Positive changes in neuoplasticity helps counter declines in CNS conductivity by relaying information to both upper limbs. An additional hypothesis as to how cross-education occurs suggests that unilateral training can cause a \"spill over\" of neural drive to the untrained side to induce changes in the control system. Unilateral strength training allows these changes to the control system to be accessed by the opposite limb [22]. Further research is necessary to fully understand the neurophysiology mechanisms behind cross-education for the MS population. Regardless, the high repetitions of our training task, supports the theory that, in presence of CNS damage, repetitive, resistance exercises with the affected limb causes the brain to develop new neural pathways controlling motor functions [28]. The development of new neural pathways leads to functional restoration in overall motor functions (i.e., both limbs) and is foundational to robotic rehabilitation. Even though comparing traditional and robotic rehabilitation was not the purpose of this study, we acknowledge that the efficacy of robotic rehabilitation compared to the standard of care has been long debated [13,25]. However, many studies demonstrated that robotics ensure those advantages already presented in Section 1: repeatable and controlled conditions even in long lasting trainings, increased spatial and temporal accuracy, and the resultant possibility to develop high-reliable performance-based tailored programs. The adaptive program focused on reducing tracking error/increasing motor accuracy rather than increasing muscular strength. However, in the beginning, the level of upper-limb impairment of our specific sample was unknown. Consequently, our underestimation of MS individuals' performance took the algorithm to converge quickly towards the resistive modality. Because of this limitation, the assistive phase was not deeply exploited, and the training was mainly resistive for all participants. Even in the resistive modality, the exerted repulsive torques were modulated by participants' online performance. The resistive progressions used in this research could have acted as a strength training model, requiring the muscles of the forearm to increase activation to complete each lap. Over the 4-week duration of the training, there was an increase in isometric wrist strength in each of the 4 planes, with an average increase in the trained limb of 28% for flexion, 11% for extension, 44% for radial and ulnar deviation. Only radial deviation showed statistically significant improvements in the control limb. Although not significant, the other directions demonstrated an average increase of 22%, 19%, 56%, for flexion, extension and ulnar deviation, respectively, which could have clinical or functional significance.