Frontal Non-Invasive Neurostimulation Modulates Antisaccade Preparation in Non-Human Primates

A combination of oculometric measurements, invasive electrophysiological recordings and microstimulation have proven instrumental to study the role of the Frontal Eye Field (FEF) in saccadic activity. We hereby gauged the ability of a non-invasive neurostimulation technology, Transcranial Magnetic Stimulation (TMS), to causally interfere with frontal activity in two macaque rhesus monkeys trained to perform a saccadic antisaccade task. We show that online single pulse TMS significantly modulated antisaccade latencies. Such effects proved dependent on TMS site (effects on FEF but not on an actively stimulated control site), TMS modality (present under active but not sham TMS on the FEF area), TMS intensity (intensities of at least 40% of the TMS machine maximal output required), TMS timing (more robust for pulses delivered at 150 ms than at 100 post target onset) and visual hemifield (relative latency decreases mainly for ipsilateral AS). Our results demonstrate the feasibility of using TMS to causally modulate antisaccade-associated computations in the non-human primate brain and support the use of this approach in monkeys to study brain function and its non-invasive neuromodulation for exploratory and therapeutic purposes

Unidirectional ocular flutter

Ocular flutter is a rare abnormal eye movement consisting of irregular bursts of to‐and‐fro bidirectional horizontal saccades and is frequently encountered in association with cerebellar symptoms. We present a patient with a probable post‐infectious ocular flutter that exhibited characteristics not previously reported in the literature. Bursts of ocular flutter consisted almost exclusively of initial rightward saccades and were clearly influenced by orbital eye position and the presence of a visual stimulus. The most recent models of saccadic oscillations do not provide an explanation for such atypical features, especially for the systematic directional bias. Based on existing experimental data, we propose that dysfunction of vermal pause neurons in an unstable saccade network could account for such atypical characteristics

Reproduction of self-rotation duration

International audience10 The vestibular system detects the velocity of the head even in complete darkness, and thus contributes to spatial orientation. However, during vestibular estimation of linear passive self-motion distance in darkness, healthy human subjects mainly rely on time, and they replicate also stimulus duration when required to reproduce previous self-rotation. We then made the hypothesis that the perception of vestibular-sensed motion duration is embedded within encoding of motion kinetics. The ability to estimate time during passive self-motion in darkness was examined with a self-rotation reproduction paradigm. Subjects were required to replicate through self-driven transport the plateau velocity (30, 60 and 90 • /s) and duration (2, 3 and 4 s) of the previously imposed whole-body rotation (trapezoid velocity profile) in complete darkness; the rotating chair position was recorded (500 Hz) during the whole trials. The results showed that the peak velocity, but not duration, of the plateau phase of the imposed rotation was accurately reproduced. Suspecting that the velocity instruction had impaired the duration reproduction, we added a control experiment requiring subjects to reproduce two successive identical rotations separated by a momentary motion interruption (MMI). The MMI was of identical duration to the previous plateau phase. MMI duration was fidelitously reproduced whereas that of the plateau phase was hypometric (i.e. lesser reproduced duration than plateau) suggesting that subjective time is shorter during vestibular stimulation. Furthermore, the accurate reproduction of the whole motion duration, that was not required, indicates an automatic process and confirms that vestibular duration perception is embedded within motion kinetics. 25 26 The contribution of the vestibular system to orientation and 27 localization of the body in space has long been suggested, 28 and recent studies have shown that indeed, for passive angular 29 whole-body motion in darkness [3,12,13,16,21,22], the brain can 30 retrieve the traveled path amplitude from vestibular information 31 (together with somatosensory information). These estimates of 32 angular self-motion are probably computed first by time integra-33 tions (from the vestibular signal of acceleration to position) and 34 then through the more topologic (spatial and temporal) "path 35 integration" [17,18]. 36 However, in our experiments on distance estimation of lin-37 ear transport [2,11], subjects used time (they mentally counted) 38 to complement vestibular information in order to evaluate their 39 self-motion magnitude. Furthermore, when required to repro-40 * Correspondence to: LDC-EPHE, (I. Israël). duce self-rotation amplitude, subjects reproduced also motion 41 duration (and peak velocity) [10,21]. We then made the hypoth-42 esis that time was reproduced "automatically", i.e. that the 43 perception of vestibular-sensed motion duration is embedded 44 within the encoding of motion kinetics and cannot be processed 45 independently during motion. 46 Subjects were required to reproduce the plateau duration of 47 the previously imposed rotation, in complete darkness. In order 48 to examine also the effect of motion velocity on time estimate, 49 different plateau velocities were used, and the subjects had to 50 replicate both the duration and the velocity of the plateau. The 51 aim of the plateau segment (stimulus shorter than 5 s) was to 52 provide target time intervals start/end cues through the motion 53 inertial acceleration steps per se, thus without additional sensory 54 input in order to avoid the possible different sensory modality 55 influence [19] on vestibular time estimation. 56 Sixteen healthy volunteers (eight men and eight women)

Molecular analyses of the LRRK2 gene in European and North African autosomal dominant Parkinson's disease

Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been identified in families with autosomal dominant Parkinson's disease (ADPD), the most common of which is the p.G2019S substitution that has been found at varying frequencies worldwide. Because of the size of the LRRK2 gene, few studies have analysed the entire gene in large series of ADPD families

The pleiotropic movement disorders phenotype of adult ataxia-telangiectasia

International audienceOBJECTIVE:To assess the clinical spectrum of ataxia-telangiectasia (A-T) in adults, with a focus on movement disorders.METHODS:A total of 14 consecutive adults with A-T were included at 2 tertiary adult movement disorders centers and compared to 53 typical patients with A-T. Clinical evaluation, neurophysiologic and video-oculographic recording, imaging, laboratory investigations, and ATM analysis were performed.RESULTS:In comparison with typical A-T cases, our patients demonstrated later mean age at onset (6.1 vs 2.5 years, p < 0.0001), later loss of walking ability (p = 0.003), and longer survival (p = 0.0039). The presenting feature was ataxia in 71% and dysarthria and dystonia in 14% each. All patients displayed movement disorders, among which dystonia and subcortical myoclonus were the most common (86%), followed by tremor (43%). Video-oculographic recordings revealed mostly dysmetric saccades and 46% of patients had normal latencies (i.e., no oculomotor apraxia) and velocities. The α-fetoprotein (AFP) level was normal in 7%, chromosomal instability was found in 29% (vs 100% of typical patients, p = 0.0006), and immunoglobulin deficiency was found in 29% (vs 69%, p = 0.057). All patients exhibited 2 ATM mutations, including at least 1 missense mutation in 79% of them (vs 36%, p = 0.0067).CONCLUSION:There is great variability of phenotype and severity in A-T, including a wide spectrum of movement disorders. Karyotype and repeated AFP level assessments should be performed in adults with unexplained movement disorders as valuable clues towards the diagnosis. In case of a compatible phenotype, A-T should be considered even if age at onset is late and progression is slo

Novabrik

CCMC Evaluation Report 12833-RPeer reviewed: NoNRC publication: Ye