The influence of neuromuscular electrical stimulation (NMES) parameters on brain activation has been scarcely investigated. We aimed at comparing two frequently used NMES protocols-designed to vary in the extent of sensory input. Whole-brain functional magnetic resonance imaging was performed in sixteen healthy subjects during wide-pulse high-frequency (WPHF, 100 Hz–1 ms) and conventional (CONV, 25 Hz–0.05 ms) NMES applied over the triceps surae. Each protocol included 20 isometric contractions performed at 10% of maximal force. Voluntary plantar flexions (VOL) were performed as control trial. Mean force was not different among the three protocols, however, total current charge was higher for WPHF than for CONV. All protocols elicited significant activations of the sensorimotor network, cerebellum and thalamus. WPHF resulted in lower deactivation in the secondary somatosensory cortex and precuneus. Bilateral thalami and caudate nuclei were hyperactivated for CONV. The modulation of the NMES parameters resulted in differently activated/deactivated regions related to total current charge of the stimulation but not to mean force. By targeting different cerebral brain regions, the two NMES protocols might allow for individually-designed rehabilitation training in patients who can no longer execute voluntary movements. Neuromuscular electrical stimulation (NMES) consists of a series of intermittent electrical stimuli applied over the muscle or the nerve trunk in order to elicit isometric muscle contractions. NMES has emerged as an efficient tool to induce activity-dependent plasticity in neural circuits in both healthy subjects 1, 2 and hypoactive patients with stroke 3–5. For instance, changes in corticospinal excitability resulting from a single session of NMES have been reported for a variety of upper 6, 7 and lower 8 limb muscles. Accordingly, functional magnetic resonance imaging (fMRI) investigations revealed a widespread brain activation pattern in response to NMES of different muscle groups, including the contralateral primary motor (M1) and sensory (S1) cortices, secondary somatosen-sory area (S2), supplementary motor area (SMA) and prefrontal cortex 9–13. Despite the promise of NMES as a tool for driving neuroplasticity and improving motor function 3–5 , the influence of stimulation parameters on the magnitude of sensory inputs to the brain has been scarcely investigated. A few studies have only reported a dose-response relationship between either stimulation intensity 10, 14 or pulse frequency 15 and brain activation patterns. From a neuromuscular point of view, NMES-induced isometric contractions may arise from the direct activation of motor axons (i.e., efferent pathway) and/or from the recruitment of motoneurons in the spinal cord through the depolarization of sensory axons (i.e., afferent pathway). It has been reported that NMES parameters, such as stimulation intensity, pulse frequency and pulse duration, affect the relative contribution of efferent and afferent pathways to force production 16. Conventional (defined hereafter as CONV) NMES protocols typically consist of short pulses (<400 µs) applied at frequencies between 15 and 40 Hz and high stimulation intensities 17. This combination of stimulation parameters primarily elicits contractions