## 4 Discussion
### Physiological Implications  
Notwithstanding the reduced sample of patients evaluated in this study, we verified greater variations in the amplitude of M waves elicited in paretic than non-paretic biceps brachii. Such findings might provide evidence of changes in the organization of the neuromuscular system following stroke, specifically of increases in the innervation ratio of paretic muscles, probably due to muscle fiber reinnervation. According to a recent longitudinal study investigating motor unit size index (MUSIX) in patients with amyotrophic lateral sclerosis (ALS), the muscle reinnervation process is associated with the clinical preservation of muscle strength [14]. Motor units' enlargements, however, likely account for stroke survivors' inability to finely control movements with the paretic limb. The force generated by single motor units with respect to total muscle force reflects the quantal increment in muscle force, indicating how finely force may be regulated. In addition, the amount of force produced by individual units is proportional to the number of muscle fibers they supply [15], i.e., the smaller the number of muscle fibers innervated by a single motoneuron, the smaller the force produced per motor unit. Therefore, a muscle with a relatively low innervation ratio would produce finer increments in force than muscles with higher innervation ratios for similar synaptic inputs. Our group results showed that the side difference in _increment amplitudes_ was about 0.7% (cf. Figure 3A). Such a value can indicate the greater amount of additional muscle fibers elicited in the paretic muscle with respect to the non-paretic muscle for similar, relative increases in the stimulation intensity. In this hypothesis, if we translate this side difference in terms of incremental force, the biceps brachii of paretic limbs would produce greater relative force increments with respect to non-paretic limbs. Hence, the motor units' enlargement following a stroke may preserve the muscle strength but also hinder the ability of stroke survivors to produce increments in force as finely as healthy muscles.  
The analysis proposed in the present study, combining surface EMG with incremental electrical stimulation, seems to provide an effective means for assessing structural adaptations in the neuromuscular system of stroke survivors. Previous accounts investigated muscle reinnervation in stroke survivors by applying protocols that may not be suitable in the clinical field. The use of invasive techniques (e.g., single-fiber electromyography) poses greater risk and discomfort for patients than non-invasive methods, besides probably hindering their recruitment. Another limitation of the methodologies previously applied is to perform assessments requiring voluntary contractions [9,10]. A common sequela of stroke is a complete or partial paralysis of one side of the body (hemiplegia and hemiparesis, respectively) [17]. Therefore, protocols involving neuromuscular electrical stimulation allow the evaluation of stroke survivors unable to contract the muscles voluntarily.  
Hence, the experimental protocol applied in the present study is expected to further our understanding of stroke-induced changes as well as to help clinicians and therapists monitor disease progression and rehabilitative interventions in stroke survivors. Our findings indeed suggested changes in the organization of the neuromuscular system in the patients evaluated.