van Essen et al. Mefloquine induced motor deficits Figure 2 | Perception of complex rhythms is not impaired by the intake of mefloquine. (A) Schematic representation of the rhythm perception task. Two rhythms consisting of four tones are separated by a pause of 2 s. One of the rhythms has a timing perturbation of the second tone.This perturbation varies in size (0, 10, 25, 50, and 100 ms).The subject has to determine whether the rhythms are identical or different. (B)The ability to distinguish complex rhythmic stimuli as a function of perturbation length (ms) is reflected in the number of errors made per type of perturbation. Blue squares indicate mean % of errors ± SEM (error bars) before mefloquine intake and red squares indicate mean % of errors ± SEM (error bars) 24 h after mefloquine intake (n = 9). In the reflex blinking sessions 15 blinks were randomly evoked in 1 s trials each. For each reflex blink three temporal aspects, the onset, peak time velocity, and peak time amplitude were determined. The onset of the blink is the time between the start of the US and the start of the eyelid movement, the peak time velocity is the time between the start of the US and the moment that the eyelid reaches the maximal velocity (which is determined after differentiating the eyelid trace), and the peak time amplitude is the time between the start of the US and the moment that the eyelid reaches the maximal amplitude (Figure 3A). rtom Inrael:gn -yeIlbkn IdnocItInogn Eye-blink conditioning is an associative learning task (Gormezano et al., 1962), in which a reflex blink (induced by US) is associated to a tone (conditioned stimulus: CS). Repetitive paired presentation of the CS with the US results in the gen- eration of a conditioned response (CR), a closure of the eye- lid upon presentation of CS (Figure 4A). The olivocerebellar system is involved in this conditioning of the eyelid response (Medina et al., 2000). For this task the participants were equipped with a headphone, video goggles (Logitech, USA), and a puff nozzle. The headphone and video goggles provided additional entertainment in order to Figure 3 | reflex blinking is not affected by the intake of mefloquine. (A) Left panel: Schematic drawing of eye-blink recording system. A gold plated neodymium magnet was attached to the edge of the upper eyelid (red circle), while a magnetoresistive sensor was attached at the edge of the orbit below the right lower eyelid (green circle). A blink was induced by a small air-puff (unconditioned stimulus: US). An increased magnetic force is detected by the sensor during closure of the eyelid. Right panel: eyelid movement recording of an unconditioned response (UR).Three temporal aspects of the reflex blink were determined: the onset, peak time velocity and peak time amplitude (red arrows). Figure is adopted from Smit et al. (2008). (B) Histogram of eye-blink timing parameters before (blue bars) and 24 h after the intake of mefloquine (red bars). (C) Histogram of standard deviations of the measured eye-blink timing parameters before (blue bars) and 24 h after the intake of mefloquine (red bars). Histograms show mean and SEM (n = 9). ensure that attention deficits and anxiety would not interfere with the eye-blink conditioning session (Smit et al., 2008). In the eye- blink conditioning sessions, participants received eight blocks of eight 2 s trials. Each block consisted of one air-puff only trial (US only) as described above, one trial in which the tone (CS) was presented alone (CS only) and six trials in which tone and air- puff were paired. In these paired trials the 20 ms air-puff ended simultaneously with the 520 ms tone by presenting it with a 500 ms delay after onset of the tone (Figure 4A). For each CS only and paired trial the presence or absence of a CR was determined. For each subject and experiment we calculated the percentage of CRs Frontiers in Neuroscience | Neuropharmacology November 2010 | Volume 4 | Article 191 | 4