Both whole-body rotation and visual flow induce cardiovascular autonomic response in human, but visual response is overridden by vestibular stimulation.

While the influence of the vestibular and extra-vestibular gravity signals on the cardiovascular system has been demonstrated, there is little evidence that visual stimuli can trigger cardiovascular responses. Furthermore, there is no evidence of interaction between visual and vestibular signals in autonomic control, as would be expected since they are highly integrated. The present study explored the cardiovascular responses to vestibular and visual stimuli in normal subjects. We hypothesized that the visual stimuli would modify the cardiovascular response to vestibular stimulation, especially when the latter is ambiguous with respect to gravity. Off-Vertical-Axis-Rotation (OVAR) was used to stimulate vestibular and extra-vestibular receptors of gravity in 36 healthy young adults while virtual reality was used for visual stimulation. Arterial pressure (AP), respiratory rate and ECG were measured. The analysis accounted for the respiratory modulation of AP and heart rate (HR). Vestibular stimulation by OVAR was shown to modulate both mean arterial pressure (MAP) and HR, while the visual stimulation was significantly affecting HR modulation, but not MAP. Moreover, the specific visual effect was present only when the subjects were not in rotation. Therefore, visual stimulation is able to modulate the heart rate, but is overridden by vestibular stimulation due to real movement.

A new toolbox to compare target localizations for non-invasive brain stimulation: An application of rTMS treatment for auditory hallucinations in schizophrenia.

BACKGROUND: Most repetitive transcranial magnetic stimulation (rTMS) studies aiming to reduce auditory verbal hallucinations (AVH) in schizophrenia target the left temporo-parietal junction (TPJ), but the efficacy of this approach remains controversial. The observed differences in efficacy could be attributed to inaccurate target localization. Here, to precisely quantify anatomical bias induced by localization method, we developed a free open-source software (GeodesicSlicer) that computes shortest curved path (i.e. geodesic) between rTMS targets. Here we compare a personalized target with accurate anatomical criteria with a standardized target based on the 10-20 EEG system (the middle between T3 and P3 electrodes: T3P3). METHODS: We compare in 69 patients with schizophrenia the geodesic distances of two approaches for rTMS target localization within the left TPJ. In addition, we characterize the personalized target according to the 10-20 EEG system. RESULTS: A differential of 3 cm in term of geodesic distance between rTMS localization approaches was observed. Moreover, this personalized target to treat AVH is located at 25% in the T3-P3 axis. CONCLUSIONS: This software for rTMS localization comparison demonstrates the difference between standardized and personalized rTMS target. This difference has the potential to explain a part of the dissonant clinical results found in previous rTMS studies.

GeodesicSlicer: a Slicer Toolbox for Targeting Brain Stimulation.

NonInvasive Brain Stimulation (NIBS) is a potential therapeutic tool with growing interest, but neuronavigation-guided software and tools available for the target determination are mostly either expensive or closed proprietary applications. To address these limitations, we propose GeodesicSlicer, a customizable, free, and open-source NIBS therapy research toolkit. GeodesicSlicer is implemented as an extension for the widely used 3D Slicer medical image visualization and analysis application platform. GeodesicSlicer uses cortical stimulation target from either functional or anatomical images to provide functionality specifically designed for NIBS therapy research. The provided algorithms are tested and they are accessible through a convenient graphical user interface. Modules have been created for NIBS target determination according to the position of the electrodes in the 10-20 system electroencephalogram and calculating correction factors to adjust the repetitive Transcranial Magnetic Stimulation (rTMS) dose for the treatment. Two illustrative examples are processing with the module. This new open-source software has been developed for NIBS therapy: GeodesicSlicer is an alternative for laboratories that do not have access to neuronavigation system. The triangulation-based MRI-guided method presented here provides a reproducible and inexpensive way to position the TMS coil that may be used without the use of a neuronavigation system.

Impact of rTMS on functional connectivity within the language network in schizophrenia patients with auditory hallucinations.

This exploratory study investigated the functional connectivity (FC) in the language network in schizophrenia patients (SZ) with auditory verbal hallucinations (AVHs), and the therapeutic efficacy of rTMS on it. Eleven SZ with AVHs and 10 healthy controls (HC) underwent two fMRI sessions using a speech listening paradigm. SZ received 20Hz rTMS following the first fMRI session. Compared to HC, SZ showed a reduced FC in the language network. While AVHs improved after 12days, no changes in FC were observed. This suggests the efficacy of high-frequency rTMS on AVH without any impact for rTMS on FC within the language network.

Somatosensory evoked potentials in the assessment of peripheral neuropathies: Commented results of a survey among French-speaking practitioners and recommendations for practice.

BACKGROUND: Somatosensory evoked potentials (SSEPs) are increasingly performed for the assessment of peripheral neuropathies, but no practical guidelines have yet been established in this specific application. STUDY AIM: To determine the relevant indication criteria and optimal technical parameters for SSEP recording in peripheral neuropathy investigation. METHODS: A survey was conducted among the French-speaking practitioners with experience of SSEP recording in the context of peripheral neuropathies. The results of the survey were analyzed and discussed to provide recommendations for practice. RESULTS: SSEPs appear to be a second-line test when electroneuromyographic investigation is not sufficiently conclusive, providing complementary and valuable information on central and proximal peripheral conduction in the somatosensory pathways. CONCLUSIONS: Guidelines for a standardized recording protocol, including the various parameters to be measured, are proposed. CLINICAL RELEVANCE: We hope that these proposals will help to recognize the value of this technique in peripheral neuropathy assessment in clinical practice.

Residual effect of zolpidem 10 mg and zopiclone 7.5 mg versus flunitrazepam 1 mg and placebo on driving performance and ocular saccades.

RATIONALE: Studies report contradictory results concerning the residual effects of zolpidem and zopiclone. Moreover, residual effects of these compounds on healthy subjects have not yet been simultaneously assessed. OBJECTIVE: The present study with healthy subjects investigated the residual effects of zolpidem 10 mg and zopiclone 7.5 mg on driving performance and on ocular saccade and compared them to those under flunitrazepam 1 mg and placebo. METHODS: The study involved 16 subjects divided into two groups, a 9:00 a.m. group and a 11:00 a.m. group, in a balanced, double-blind, cross-over design. RESULTS: In the 9:00 a.m. group, zolpidem had no residual effects while zopiclone and flunitrazepam both impaired driving performance (P < 0.001 for both) and increased saccadic latency (P < 0.005; P = 0.052, respectively). Zopiclone impaired driving performance 5 times less than did flunitrazepam. In the 11:00 a.m. group, zolpidem and zopiclone had no residual effects, while flunitrazepam increased saccadic latency (P = 0.065) but did not impair driving performance. CONCLUSIONS: Zopiclone and flunitrazepam had residual effects in the first part of the morning, whereas zolpidem had no residual effects. The hierarchical character of the effects of the molecules differed according to the test administered. This is probably linked more to drug-induced specific alterations than to different sensitivities of the tests.

Saccadic and smooth-pursuit eye movements in deficit and non-deficit schizophrenia.

We have analyzed eye movement performances in schizophrenics showing primary negative or deficit symptoms (n=16) and non-deficit schizophrenics (n=55), and compared them with those of controls (n=34) in order to study the relationships between negative symptoms and eye movement abnormalities. Patients were subtyped into deficit and non-deficit subgroups using the Schedule for the Deficit Syndrome. Three oculomotor paradigms were used: smooth pursuit, a reflexive saccade paradigm and an antisaccadic task. The smooth pursuit gain was significantly decreased (and the rate of catch-up saccades increased) in schizophrenics as compared with controls, but no difference was observed between patient groups. In the reflexive saccade paradigm, no difference was found between controls and patients, except for latency in deficit patients. In the antisaccade paradigm, the number of errors and the latency of successful antisaccades were significantly increased in schizophrenics as compared with controls. The latency of successful antisaccades in both directions was significantly increased in deficit patients as compared with non-deficit patients. The latency of rightward successful antisaccades was significantly increased as compared with the latency of leftward antisaccades in deficit patients only. However, when patients were classified into negative and non-negative groups using the PANSS, no difference was found in the antisaccade paradigm. Smooth pursuit impairment does not seem to depend on the primary enduring negative symptoms.In deficit schizophrenics, the abnormalities observed in the antisaccadic task are consistent with prefrontal dysfunction, and may suggest parietal lobe dysfunction as well.

Motion sickness susceptibility correlates with otolith- and canal-ocular reflexes.

Since motion sickness (MS) never occurs in individuals who lack functional vestibular apparatus, it has been suggested that MS susceptible individuals have more sensitive vestibular systems than non-susceptible people. However, previous investigations involving only stimulation of the semi-circular canals have been inconclusive. We measured gain and time constant (TC) of horizontal canal-ocular reflex (COR) and magnitude of otolith-ocular reflex (OOR). We found that MS susceptibility was not correlated to COR gain but was negatively correlated to OOR magnitude. Thus, MS susceptible individuals do not have more sensitive vestibular systems. We also found a positive correlation between MS susceptibility and TC. We hypothesize that central vestibular integration (velocity storage mechanism), by increasing low frequency vestibular inputs, would favour MS.

Picture naming without Broca's and Wernicke's area.

Lexical and semantic retrieval was investigated in normal volunteers with PET by comparing picture confrontation naming and verb generation related to the same pictures. Conjunction analysis of the naming and verb generation uncovered a common network including the occipito-temporal ventral pathway for object recognition, and the bilateral anterior insula, SMA and precentral gyrus for coordination, planning and overt word production. Naming and verb generation highlighted two different patterns: verb generation showed specific implication of Broca and Wernicke's areas, whereas naming specifically relied on the primary visual areas, the right fusiform and parahippocampal gyri and the left anterior temporal region. These results indicate that speech does not necessarily involve the Wernicke-Broca's language network and testify that naming relies on an early developmental language network.

Hyper- and hypogravity alter posture in rats compensated on Earth for a vestibular asymmetry.

Head posture and neck muscle activity (EMGs) were examined in unilateral (UL) and bilateral (BL) vestibularly lesioned rats in hypergravity (1.7 g) and hypogravity (0 g) during parabolic flights. Compared with BL rats taken as control, the head and the body of UL deviated toward the lesion side at 0 g and toward the intact side at 1.7 g. Recorded in head fixed condition, left and right EMGs remained symmetrical in BL while UL rats displayed an asymmetry between left and right muscles at 1.7 g, but not at 0 g. These results demonstrate that an experimental otolithic asymmetry, compensated on Earth, can become unbalanced in altered gravity. Paradoxically, the utricular system appears to play a major role in that process.

Otolithic and tonic neck receptors control of limb blood flow in humans.

The aim of this study was to evaluate the role of otolithic receptors and neck mechanoreceptors on the control of the cardiovascular system. We measured calf (CBF) and forearm blood flow (FBF) by strain-gauge plethysmography, mean arterial pressure (MAP), and heart rate (HR) in 12 healthy subjects in two body positions (lying prone and on the left side) and three head positions (reference, flexion, and extension). When the subjects were lying prone, CBF and FBF were lower in head flexion (5.2 +/- 0.6 and 3.2 +/- 0.4 ml.min-1.100 ml-1, respectively) than in reference position (5.8 +/- 0.4 and 3.8 +/- 0.3 ml.min-1.100 ml-1; P < 0.05), with no significant difference in MAP and HR. When the subjects were lying on the side, changing the head position from reference to flexion significantly increased FBF (from 3.7 +/- 0.2 to 4.2 +/- 0.4 ml.min-1. 100 ml-1), MAP (from 97.2 +/- 3.3 to 102.4 +/- 5.8 mmHg), and HR (from 63.7 +/- 1.4 to 65.9 +/- 2.5 beats/min; P < 0.05). Because otolithic receptors and neck mechanoreceptors are involved when the subjects are lying prone, and otolithic receptors are not involved when the subjects are lying on the side, the results suggest that otolithic and neck mechanoreceptors exert significant influences over the cardiovascular system.

Motion sickness during off-vertical axis rotation: prediction by a model of sensory interactions and correlation with other forms of motion sickness.

Motion sickness (MS) susceptibility of 108 normal subjects was measured during off-vertical axis rotation (OVAR) as a function of angular velocity (60-180 degrees/s). The chair rotated about a longitudinal axis tilted 30 degrees with respect to gravity. For each velocity, we measured the duration of exposure necessary to evoke a moderate malaise, with a limit of 30 min. MS appeared the fastest at a rotation velocity of 105 degrees/s; higher or lower velocities were less provocative. These results are in good agreement with predictions made by Zupan et al. [in ICANN'94, Springer-Verlag, 1995] by means of a MS mathematical model derived from a model of sensory interactions [Droulez and Darlot, in Attention and Performance, Vol. 13, Lawrence Erlbaum, Hillsdale, 1989]. We also found that MS susceptibility during OVAR is positively correlated with susceptibility to other forms of MS. Since OVAR induces sensory messages very different from those induced by other provocative stimulations, this could suggest that the sensitivity of a common final vegetative locus is an important factor of the individual differences in susceptibility to MS.

Motion sickness occurrence does not correlate with nystagmus characteristics.

The purpose of this study was to test the hypothesis whereby eye movements as such may be an important factor in the development of motion sickness (MS). The horizontal eye movements of 27 subjects were measured during earth vertical axis rotation (EVAR) and during off vertical axis rotation (OVAR). Two groups were set up, one including subjects who suffered severe MS during the test, and the other including subjects with no MS symptoms. We found no differences in nystagmus parameters (EVAR: gain and time constant; OVAR: eye velocity modulation and eye position modulation) between the MS and the non-MS groups. We can conclude that eye movements are not involved in the development of MS.

Cortical networks for working memory and executive functions sustain the conscious resting state in man.

The cortical anatomy of the conscious resting state (REST) was investigated using a meta-analysis of nine positron emission tomography (PET) activation protocols that dealt with different cognitive tasks but shared REST as a common control state. During REST, subjects were in darkness and silence, and were instructed to relax, refrain from moving, and avoid systematic thoughts. Each protocol contrasted REST to a different cognitive task consisting either of language, mental imagery, mental calculation, reasoning, finger movement, or spatial working memory, using either auditory, visual or no stimulus delivery, and requiring either vocal, motor or no output. A total of 63 subjects and 370 spatially normalized PET scans were entered in the meta-analysis. Conjunction analysis revealed a network of brain areas jointly activated during conscious REST as compared to the nine cognitive tasks, including the bilateral angular gyrus, the left anterior precuneus and posterior cingulate cortex, the left medial frontal and anterior cingulate cortex, the left superior and medial frontal sulcus, and the left inferior frontal cortex. These results suggest that brain activity during conscious REST is sustained by a large scale network of heteromodal associative parietal and frontal cortical areas, that can be further hierarchically organized in an episodic working memory parieto-frontal network, driven in part by emotions, working under the supervision of an executive left prefrontal network.

Low intensity galvanic vestibulo-ocular reflex in normal subjects.

An electrical stimulation in man applied between the two mastoids could facilitate the distinction between labyrinthine and retrolabyrinthine lesions by stimulating directly the primary vestibular afferences. However, for this test to be really effective in current medical practice, the results obtained in normal subjects must be symmetrical and reproducible one day to another. The ocular responses induced by a constant electrical stimulation of 2.5 mA, applied between the two mastoids for 30 s (electrically evoked vestibulo-ocular reflex [EVOR]), in one direction and the other, were quantified in ten healthy subjects. Each subject was studied in two different sessions separated by 1 week. Horizontal eye movements were recorded in darkness by an infrared light reflection eye-tracking system. Slow-phase velocity and nystagmus frequency were about 20% higher when the cathode was on the right mastoid than when it was on the left mastoid. This directional preponderance (DP) displayed large individual differences between the two sessions. The reproducibility of the reflectivity (mean of right and left EVOR) was high (r about 0.8). The weak reproducibility of the DP makes the EVOR at weak intensity inadequate to evaluate unilateral vestibular hypofunction. On the other hand, because of the high reproducibility of reflectivity, the EVOR should be effective in detecting bilateral vestibular hypofunction. Moreover, because of the weak intensity of stimulation, no local anaesthesia is needed so the manoeuvre is easy to repeat in case of chronic diseases.

Is there a relationship between odors and motion sickness?

The aim of this study was to evaluate the relationship between olfaction and motion sickness. A sample of 18 participants was recruited and submitted to three sessions of nauseogenic stimulations: off vertical axis rotation (OVAR), performed under conditions of olfactory stimulation with limonene (pleasant odor), petrol (unpleasant odor) or distilled water (as a control). Motion sickness was assessed before, during and after each OVAR session. In addition, participants were asked to evaluate the intensity and hedonic valence of four odors (geraniol, limonene, butanol, petrol) as well as distilled water (as a control) before and after each OVAR session. Our analysis showed that OVAR has consistently increased the induced-motion sickness. However the addition of an odor that is pleasant or unpleasant during the rotation did not affect the occurrence of motion sickness symptoms compared to the control condition. Our results also showed that intensity of odors was significantly increased after OVAR and the intensity was significantly higher for unpleasant odors than for pleasant one. For the hedonicity, OVAR made unpleasant odors more unpleasant (p<0.0001) while it made limonene odor slightly more pleasant (p<0.05). The present study highlighted the lack of influence of odors in motion-induced sickness but an impact of a nauseogenic test on olfactory perception.

Two-day treatment of auditory hallucinations by high frequency rTMS guided by cerebral imaging: a 6 month follow-up pilot study.

BACKGROUND: Recently, repetitive Transcranial Magnetic Stimulation (rTMS) has been introduced as an alternative treatment for auditory hallucinations in schizophrenic patients that fail to respond to antipsychotics. Until now, application of rTMS has been at low frequency, and most commonly applied to the left temporoparietal cortex. This 6-month follow-up pilot study was performed to demonstrate the efficacy of high frequency rTMS guided by anatomical and functional Magnetic Resonance Imaging (MRI). METHODS: Eleven patients with schizophrenia (DSM-IV) were treated with high frequency (20 Hz) rTMS delivered over 2 days; they were then followed for 6 months. The target area was identified by fMRI as the highest activation cluster along the posterior part of the left superior temporal sulcus from the BOLD signal of each subject during a language task. RESULTS: A significant reduction in global severity and frequency of auditory hallucinations between baseline and post-treatment day 12 was observed. Auditory hallucinations were entirely relieved at 6-month follow-up in 2 patients. The treatment was well tolerated in all patients. CONCLUSIONS: This is the first study reporting successful treatment of auditory hallucinations with 20 Hz rTMS. The efficacy at short term, the strength of the clinical response, the persistence of therapeutic effect over a 6-month follow-up, the safety profile, and the short duration of treatment present a considerable therapeutic gain compared to low frequency rTMS.

Total sleep deprivation can increase vestibulo-ocular responses.

The effect of sleep deprivation on the vestibular function is largely unknown. Some studies have found that postural balance or vestibular reflexes are decreased in sleep-deprived subjects while others found no change. The aim of this study was to evaluate the effect of sleep deprivation on the vestibulo-ocular reflex (VOR). Horizontal eye movements were recorded in healthy subjects during earth vertical axis rotation in darkness once after an ordinary night sleep and once after 26-29 h of sleep deprivation. In the first experiment (n = 8), for which rotation was a 60 degrees s(-1) velocity step, sleep deprivation induced a significant increase in VOR gain. In the second experiment (n = 12), for which rotation was sinusoidal (0.2 Hz +/- 25 degrees s(-1)), sleep deprivation induced no significant modification in VOR gain. The difference between the two studies was the abrupt onset of the step stimulation in comparison with the sinusoidal rotation. Because of its unexpected onset and the potential threat to postural balance, the step stimulation may activate the system specialized in reorienting attention towards salient or behaviourally relevant events. This system includes the right temporoparietal cortex, an area also involved in VOR control. A number of studies have found that sleep deprivation alters the activity of this cortical area during attentional tasks. It is therefore our hypothesis that the difference between the effects of these two vestibular stimulations results from a sleep deprivation-induced modulation of the right temporoparietal cortex.