Transcutaneous Electrical Nerve Stimulation for Restoring Somatotopic Sensory Feedback in Lower Limb Amputees and Improving Phantom Limb Perception

All patients enrolled in the study will receive the same treatment as no randomization is planned. For each patient, the study will consist of two 60-minute sessions per day, except for the evaluation ones which are expected to last approximately 90 minutes, five days per week for a total duration of 4 weeks. The rehabilitation will imply both a TENS treatment and a conventional one.

1. Mapping sessions: Four Mapping sessions performed at the beginning of each week. The aim of these sessions will be to manually re-tune the perceptual thresholds and characterize the elicited sensation's location and quality on both limbs.

The patients will be asked to lie prone on a sterile medical bed in order to use an electromyography device to detect the distal end of the nerve trunk and determine the ideal electrode position for nerve stimulation (i.e., the tibial nerve in patients with Transtibial Amputation (TTA) and the sciatic one in those ones with Transfemoral Amputation (TFA)). Using anatomical landmarks, the skin surface will be identified, cleaned with an alcohol pad and the stimulation electrodes will be positioned.

The session will consist of the three following phases:

• Perceptual thresholds identification. The PW, PF, stimulus duration and rest between two consecutive stimuli will be kept constant to 500 µs, 500 Hz, 1 s and 5 s, respectively. The PA will be incremented between one stimulus and the following one from 1 mA with a step of 0.1 mA until both the sensory and motor thresholds were reached. The sensory and motor thresholds will be defined as the lowest current intensity values needed to evoke a well-defined, referred tactile sensation in the phantom limb and a visible muscle contraction, respectively. Subsequently, two different pulse amplitude values (i.e., PAmin and PAmax) will be identified respectively as the minimum and maximum current value able to evoke a well-defined and painless referred tactile sensation in the phantom limb without inducing muscular contraction. The total number of stimulus provided to the participants in this phase will be variable since perceptual thresholds values are patient-specific;
• Charge modulation. The PA, PF, stimulus duration and rest between two consecutive stimuli will be kept constant to PAmax, 150 Hz, 1 s and 5 s, respectively. The PW will be varied in the range 100-500 µs with a step of 40 µs for a total of 11 stimuli. At the end of the modulation, the PW value at which the participant can feel a well-defined and comfortable sensation will be selected;
• Frequency modulation. The PA, PW, stimulus duration and rest between two consecutive stimuli will be kept constant to PAmax, the selected value in the previous phase, 1 s and 5 s, respectively. The PF will be varied in the range 50-500 Hz with a step of 50 Hz for a total of 10 stimuli.

For each delivered stimulus, the patient will be asked to indicate the location of the evoked sensation adopting pictures representing the missing foot and leg and then to describe them. The descriptors included: a five-point scale for the naturalness ranging from unnatural to natural, a metric of the location of the sensation (i.e., superficial and/or deep), a scale from 0 to 10 for the intensity and pain of the sensation and multiple choices for the quality (touch/pression, pinch, vibration, tugging, tingling, burning, hot, cold, ankle flexion, ankle extension, toes flexion, toes extension and nothing). The Mapping protocol will be administered to the patients' both limbs randomly. 2. Stimulus Intensity Discrimination sessions: Three Stimulus Intensity Discrimination sessions will be conducted over three consecutive days during the first week.