Five tactile threshold estimates, and five heat-pain threshold estimates were obtained from each hand, and the five estimates were averaged to give threshold values for touch and pain (Fig. 1B and C) in five blocks. Within each block, tactile and contact heat-pain stimuli were delivered at random to the left or right hand, and separate threshold estimates were collected for each submodality Ibrutinib and each hand. Electrocutaneous stimuli

were delivered via 4 mm concentric electrodes (Katsarava et al., 2006), and a medically-isolated electrical stimulator (University College London Institute of Neurology, Sobell Research Department) to the tip of the finger. Pulse amplitude was held at 10 mA and pulse duration was varied to adjust the charge transferred to the skin, and thus the perceived shock

intensity. To estimate tactile detection thresholds, a staircase procedure (Levitt, 1971) was used to determine the lowest shock intensity at which a tactile stimulus could be reliably detected. Pulses of increasing width were applied until participants reported a sensation. Pulse width was successively decreased CHIR-99021 chemical structure and then increased again until exactly five of 10 stimuli were detected. This level was considered as a working estimate of each subject’s tactile threshold. Contact heat-pain stimuli were delivered to the tip of the index or middle finger using a 13 mm circular diameter Peltier-type thermode (NTE-2A, Physitemp Instruments Inc). Contact heat-pain threshold was estimated by the method of limits (Yarnitsky et al., 1995), a reliable procedure for measuring thermal pain perception thresholds (Heldestad et al., 2010). The probe temperature was fixed for 20 sec an initial level of 32 °C and gradually increased by 2 °C/sec. For safety, maximum temperature was limited to 50 °C. Participants pressed a foot pedal with their right foot when they first perceived the heat as being painful. Data for each threshold were recorded and analysed later. The method of limits was preferred for pain testing, rather than staircase

methods, because it minimises actual pain. It is therefore better tolerated by participants, and more consistent with ethical principles. Our main aim was comparison of Pre-CVS and Post-CVS for each task. Therefore, use of different threshold estimation procedures between modalities should for not affect our statistical inferences. Tactile threshold estimates were analysed using 2 × 2 univariate ANOVA with factors of CVS condition (Pre-CVS vs Post-CVS) and Side (Left hand vs Right hand). Tactile thresholds were significantly lower immediately after CVS than before [F(1,10) = 22.429, p = .001]. Significant reductions were found for both the left hand, i.e., contralateral to the stimulated hemisphere, and for the right hand, and there was no interaction between stimulation condition and hand [F(1,10) = 2.261, p = .164] ( Fig. 2A). On average, vestibular stimulation reduced tactile thresholds by 25%.