Pain inhibition by additional somatosensory input is the rationale for the widespread use of Transcutaneous Electrical Nerve Stimulation (TENS) to relieve pain. Two main types of TENS produce analgesia in animal models: high-frequency (∼50–100 Hz) and low-intensity ‘conventional’ TENS, and low-frequency (∼2–4 Hz) and high-intensity ‘acupuncture-like’ TENS. However, TENS efficacy in human participants is debated, raising the question of whether the analgesic mechanisms identified in animal models are valid in humans. Here, we used a sham-controlled experimental design to clarify the efficacy and the neurobiological effects of ‘conventional’ and ‘acupuncture-like’ TENS in 80 human volunteers. To test the analgesic effect of TENS we recorded the perceptual and brain responses elicited by radiant heat laser pulses that activate selectively Aδ and C cutaneous nociceptors. To test whether TENS has a long-lasting effect on brain state we recorded spontaneous electrocortical oscillations. The analgesic effect of ‘conventional’ TENS was maximal when nociceptive stimuli were delivered homotopically, to the same hand that received the TENS. In contrast, ‘acupuncture-like’ TENS produced a spatially-diffuse analgesic effect, coupled with long-lasting changes both in the state of the primary sensorimotor cortex (S1/M1) and in the functional connectivity between S1/M1 and the medial prefrontal cortex, a core region in the descending pain inhibitory system. These results demonstrate that ‘conventional’ and ‘acupuncture-like’ TENS have different analgesic effects, which are mediated by different neurobiological mechanisms.

IntroductionEye-tracking technology provides a reliable and cost-effective approach to characterize mental representation according to specific patterns. Mental rotation tasks, referring to the mental representation and transformation of visual information, have been widely used to examine visuospatial ability. In these tasks, participants visually perceive three-dimensional (3D) objects and mentally rotate them until they identify whether the paired objects are identical or mirrored. In most studies, 3D objects are presented using two-dimensional (2D) images on a computer screen. Currently, visual neuroscience tends to investigate visual behavior responding to naturalistic stimuli rather than image stimuli. Virtual reality (VR) is an emerging technology used to provide naturalistic stimuli, allowing the investigation of behavioral features in an immersive environment similar to the real world. However, mental rotation tasks using 3D objects in immersive VR have been rarely reported.MethodsHere, we designed a VR mental rotation task using 3D stimuli presented in a head-mounted display (HMD). An eye tracker incorporated into the HMD was used to examine eye movement characteristics during the task synchronically. The stimuli were virtual paired objects oriented at specific angular disparities (0, 60, 120, and 180°). We recruited thirty-three participants who were required to determine whether the paired 3D objects were identical or mirrored.ResultsBehavioral results demonstrated that the response times when comparing mirrored objects were longer than identical objects. Eye-movement results showed that the percent fixation time, the number of within-object fixations, and the number of saccades for the mirrored objects were significantly lower than that for the identical objects, providing further explanations for the behavioral results.DiscussionIn the present work, we examined behavioral and eye movement characteristics during a VR mental rotation task using 3D stimuli. Significant differences were observed in response times and eye movement metrics between identical and mirrored objects. The eye movement data provided further explanation for the behavioral results in the VR mental rotation task.

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