The use of neurorobotic devices into gait rehabilitative programs, including Ekso, is reported to increase the engagement and motivation of the patients while actively performing a task, and to shape the sensory-motor plasticity (SMP) and its balance between the primary motor areas (M1), and the fronto-parietal network (FPN) connectivity, thus contributing to successful gait rehabilitation. Aim of our study was to assess whether Ekso would foster the recovery of deteriorated FPN connectivity and SMP patterns involved in limb coordination during walking in a sample of patients with hemiparesis due to stroke.

Twenty outpatients were consecutively included in this study according to the following inclusion criteria: (i) age ≥55 years; (ii) a first-ever ischemic supra-tentorial stroke (confirmed by MRI scan) at least 6 months before their enrollment; (iii) an unilateral hemiparesis, with a Muscle Research Council -MCR- score ≤3; (iv) ability to follow verbal instructions, with a Mini-Mental State Examination (MMSE) >24; (v) a Modified Ashworth Scale (MAS) score ≤2; (vi) no severe bone or joint disease; and (vii) no history of concomitant neurodegenerative diseases or brain surgery.

Patients were randomly assigned to the experimental (Ekso gait training -EGT) of control group (conventional overground gait training -OGT- at a velocity matched to the Ekso gait training).

Ekso (Ekso Bionics; Richmond -CA- USA) is a wearable robot consisting of an exoskeleton framework for the lower limbs with (1) electric motors to power movement for the hip and knee joints, (2) passive spring-loaded ankle joints, (3) foot plates on which the user stands, and (4) a backpack that houses a computer, battery supply, and wired controller. A rigid backpack is an integral structural component of the exoskeleton, which provides support from the posterior pelvis to the upper back, besides carrying the computer and batteries. The exoskeleton attaches to the user's body with straps over the dorsum of the foot, anterior shin and thigh, abdomen, and anterior shoulders. The limb and pelvic segments are adjustable to the user's leg and thigh length, and the segment across the pelvis is adjustable for hip width and hip abduction angle. We preliminarily measured M1-leg excitability and SMI, which were probed using TMS pulses with a monophasic pulse configuration and peripheral nerve electric stimuli. Single magnetic pulses were given to the affected and unaffected leg-M1 using a standard figure-of-eight coil (diameter of each wing, 90 mm) connected with a high-power Magstim200 stimulator (Magstim Co, Ltd; UK).

Effective connectivity (that measures the causal influence that one brain area exerts over another under the assumption of a given mechanistic model) was assessed using a structural equation modelling (SEM). An 8-channel wireless surface EMG (sEMG) device (BTS; Milan, Italy) was used to record EMG activity from eight muscles (both tibialis anterior -TA-, soleus -S-, rectus femoris -RF-, and biceps femoris -BF). The device was also equipped with an accelerometer, put at lumbar level, to establish gait phases. Gait analysis was conducted on a 10-meter walkway.

We measured the following gait measures for both the affected and unaffected lower limb [20]: (i) step cadence (number of steps per minute; normal values 1.9±0.1 Hz);. (ii) gait cycle duration (time from one right heel strike -initial contact- to the next one -end of terminal swing; normal values 1.1±0.1 sec); (iii) stance/swing ratio (ratio between stance from heel strike to toe-off, and swing phase duration from toe-off to heel strike; normal values 1.5±0.1); .and (iv) an overall gait performance score (gait index, reflecting an approximate 60:40% distribution of stance:swing phases; normal values >90).

Inclusion Criteria:

(i) age ≥55 years; (ii) a first-ever ischemic supra-tentorial stroke (confirmed by MRI scan) at least 6 months before their enrollment; (iii) an unilateral hemiparesis, with a Muscle Research Council -MCR- score ≤3; (iv) ability to follow verbal instructions, with a Mini-Mental State Examination (MMSE) >24; (v) a Modified Ashworth Scale (MAS) score ≤2; (vi) no severe bone or joint disease; and (vii) no history of concomitant neurodegenerative diseases or brain surgery.

Exclusion Criteria:

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