Evidence of attentional impairments using virtual driving simulation in multiple sclerosis.

BACKGROUND: Detection of attentional disorders in complex situation related to daily life activities in multiple sclerosis patients needs better adapted tools than traditional cognitive assessment. OBJECTIVE: To investigate the usefulness of virtual reality assessment of attention in multiple sclerosis, especially to evaluate alertness and divided attention using driving simulation. METHODS: In this preliminary study, 11 relapsing-remitting patients (median EDSS: 2; mean disease duration of 10.3 years) and 11 healthy matched controls performed a driving simulation under three conditions (monotonous driving, divided attention driving and urban driving) where Standard Deviation of Lateral position (SDLP) was the main evaluated criteria. In comparison, traditional cognitive assessment of attentional functions was administered (SDMT, alertness and divided attention of TAP battery). Statistical non-parametric Mann-Whitney U tests were used to compare performances between groups in the two types of assessments. Exploratory correlational analyses were further conducted. RESULTS: No significant difference was observed between groups for traditional attentional assessment except for information processing speed (SDMT; p < 0.01). Considering virtual reality, patients were less efficient than controls on the primary parameter of safe driving (SDLP; p < 0.05). They also committed more errors and omissions (p < 0.01) and speed fluctuations (p < 0.01) during the divided-attention driving condition. Urban driving did not reveal difference between groups. Lack of significant correlations between traditional and virtual reality attentional assessment suggested that they do not evaluate the same cognitive processes. CONCLUSION: Patients experienced difficulties in maintaining the trajectory and the speed of the simulated vehicle which may be indicative of attentional difficulties, especially alertness and divided attention. These impairments were not revealed by the traditional cognitive assessment. Results of this preliminary study shed new light about the usefulness of virtual reality techniques and their future interest as a part of cognitive rehabilitation programs. They also highlights the need to develop driving preventive measures in MS.

Driving performance and EEG fluctuations during on-the-road driving following sleep deprivation.

The present study mainly aimed to assess whether and how sleepiness due to sleep deprivation interacts with Time on Task (ToT) effects both on electroencephalography (EEG) measures and driving performance in real driving conditions. Healthy participants performed a one hour on-the-road monotonous highway driving task while EEG was recorded continuously after one night of normal sleep and after one night of total sleep deprivation. The main outcome parameter in the highway driving test was the Standard Deviation of Lateral Position (SDLP). SDLP and EEG indices (i.e alpha and theta power spectra) increased after sleep deprivation and varied with ToT. The latter was more pronounced after sleep deprivation. Beta power spectra did not differ between conditions but increased with ToT. Changes in SDLP and EEG did not correlate significantly. We conclude that driving performance as well as fatigue and sleepiness fluctuations with ToT were more evident after sleep deprivation as compared to normal sleep.

Are eye movement abnormalities indicators of genetic vulnerability to schizophrenia?

UNLABELLED: Fifty to eighty-five percent of schizophrenic patients are impaired on ocular pursuit paradigms. However, results regarding the relatives are more discordant. The aim of this study was to investigate whether eye movement disorders could be a vulnerability marker of schizophrenia. METHOD: Twenty-one schizophrenic patients (DSM-IV), 31 first-degree relatives of those patients without schizophrenic spectrum disorders, and two groups of healthy controls matched by age and sex were included. Three oculomotor tasks (smooth pursuit, reflexive saccades and antisaccades) were used. RESULTS: Patients had a lower averaged gain (P= 0.035) during smooth pursuit than controls, made less correct visually guided saccades (P< 0.001) and more antisaccades errors (P= 0.002) than controls. In contrast, none of the comparison between the relatives and their controls was significant. CONCLUSION: Schizophrenic patients were impaired on smooth pursuit and antisaccade paradigms. None of these impairments was, however, observed in their first-degree relatives. Our results suggest that the eye movement parameters tested could not be considered as vulnerability markers for schizophrenia.

Functioning of the three attentional networks and vigilance in primary insomnia.

BACKGROUND: Results from cognitive measures in primary insomnia (PI) patients are not consistent with the difficulties in performing daily living tasks of which these patients complain about. Lack of sensitivity of the tests and the data concerning some cognitive functions may explain this discordance. The aim of the present investigation was to better characterize cognitive deficits of PI patients in order to further understand their cognitive complaints. We looked at attentional and executive function because of their high involvement in daily living tasks. METHODS: A total of 21 PI patients and 16 good sleepers completed the Attentional Network Test (ANT). We only included untreated PI patients since sleep medication could be a confounding factor when assessing cognition. RESULTS: While PI patients, compared to good sleepers, were found to have a longer overall reaction time (RT) and perform more slowly in the incongruent flanker condition (ie, conflict situation) than in the congruent condition, no group effects were observed for the variables representing the three attentional networks (ie, alerting, orienting, and executive functions). CONCLUSIONS: The present study revealed a conflict resolution deficit in untreated PI patients. This impairment may be linked to the prefrontal alterations reported in neuroimaging studies in these patients. Patients had also an impaired vigilance compared to good sleepers, likely due to the high cognitive load of the ANT. These results would serve to explain the complaints of PI patients about difficulties performing daily living tasks that are demanding and of long duration.

Electroencephalography during on-the-road driving in older untreated insomnia patients and normal sleepers.

Insomniacs report decreased performance in daily routines, which may have detrimental consequences for car driving. We compared changes over time in driving performance (measured as Standard Deviation of Lateral Position - SDLP) and background EEG between 20 untreated insomnia patients (52-70 years old) and 21 normal sleepers (54-73 years old) during a 1h on-the-road driving test after a normal night of sleep, in the morning. SDLP did not differ between groups and increased slightly over time to similar degrees in both groups. EEG alpha and beta power were lower in insomniacs as compared to normal sleepers. Alpha and beta power slightly reduced during driving in normal sleepers but remained at a constant low level in insomniacs. Changes in EEG power and SDLP were not related. It is concluded that on-the-road driving performance does not differ between older insomniacs and older normal sleepers and that changes in spectral EEG measures of cortical arousal and in driving performance are not related.

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.

Effects of zolpidem 10 mg, zopiclone 7.5 mg and flunitrazepam 1 mg on night-time motor activity.

The effects of a single dose of zolpidem (10 mg), zopiclone (7.5 mg) and flunitrazepam (1 mg) on motor activity the following 3 nights were compared to those of a placebo in a double-blind, crossover study. Thirty-three healthy subjects received medication between 10.30 and 11.30 p.m. and were asked to rise between 7.30 and 8.30 a.m. During the night under treatment, flunitrazepam, zopiclone and zolpidem significantly reduced motor activity. Changes in motor activity are quantitatively compatible with the hypothesis of reduced light sleep and wakefulness after sleep onset. During the first or second post-drug night, for zolpidem and zopiclone the opposite effect was observed, i.e. increased activity compared with placebo. These modifications cannot be explained by modified sleep structure. This last result underlines our inadequate understanding of the underlying mechanisms of motor activity during sleep. However, being sensitive and easy to use, actigraphy is an ideal technique to assess the effect of hypnotics on large populations and for long duration studies.

Residual effects of hypnotics on disengagement of spatial attention.

In an earlier study, we postulated that the residual effects of hypnotics could induce a spatial attention disengagement deficit independent of any decrease in alertness. To test this hypothesis, we compared the residual effects of zolpidem, zopiclone and flunitrazepam in two ocular saccade tests, gap and overlap. In the gap paradigm, the lateral target is illuminated 200 ms after the extinguishing of the central target. In the overlap paradigm, the central target stayed on when the lateral target was illuminated. Zopiclone increases latency in the overlap, but not in the gap test, which appears to be specific to a deficit of disengagement of spatial attention. Zopiclone impairs the saccadic precision in gap, but not in overlap, which may be interpreted as an impairment of visuospatial memory. The effects of zolpidem are limited to visuospatial impairment. The effects of flunitrazepam are massive and probably the results of a decrease in alertness.

Do zopiclone, zolpidem and flunitrazepam have residual effects on simulated task of collision anticipation?

Few studies have addressed the modifications in visual information processing brought about by taking hypnotic substances. The present experiment with healthy subjects investigated the residual effects of taking a single night-time dose of hypnotics on collision anticipation capacities the next morning. Visual sequences simulated the movement of a driver approaching an intersection where another vehicle was arriving. Ten participants had to estimate, as quickly as possible, whether the other vehicle would arrive before or after them at the intersection. They were tested after having taken a capsule of zolpidem (10 mg), zopiclone (7.5 mg), flunitrazepam (1 mg) or a placebo. The results show no residual effects of the molecules. Only flunitrazepam, a benzodiazepine with a long half-life, appears to cause subjects to focus their attention on an element which, while relevant for the task (a road sign playing the role of a spatial reference), is not used correctly.

[Eye tracking disorders in schizophrenic patients and their parents]. / La poursuite oculaire lente chez les patients schizophrènes et leurs parents.

UNLABELLED: Several studies have confirmed the existence of genetic factors in schizophrenia. However, the genotype predisposing for the disease is not known yet. Nevertheless, those genetic factors in the families of schizophrenic patients urge us to search for genetic vulnerability markers of schizophrenia. Ocular pursuit disorders, in particular, could be one of those vulnerability markers. Eye movements have been often tested in schizophrenia. Most of the schizophrenic patients have eye-tracking disorders and their biological relatives demonstrate an increased prevalence of eye-tracking impairments. The aim of the study was to research if smooth pursuit eye movements could be a vulnerability marker of schizophrenia. In order to have an indication about this hypothesis, impairments of smooth pursuit eye movements were researched in both schizophrenics and their parents. METHODS: Fifteen DSM IV schizophrenic patients stabilized at the time of the inclusion and not treated with lithium, benzodiazepines, barbiturates, or chloral hydrate; 19 parents without history of schizophrenic spectrum disorders (SADSLA and IPDE), and 2 groups of healthy subjects matched in age and sex with probands and with the parents, were included in the study. Parents only were included (fathers or mothers) in order to have an homogeneous population for the genetic risk and age. The eye-tracking paradigm used was a smooth pursuit task. The stimulus was a sinusoidal wave form moving on a horizontal line, with a frequency of 0.4 Hz and an amplitude of 30 degrees. Different parameters were measured: gain (ratio between the eye velocity and the target velocity) and saccades frequencies (catch-up saccades, back-up saccades, anticipatory saccades and square-wave-jerks). For each parameter, analysis of covariance (ANCOVA) with age as covariable was carried out. For the results reaching the significance of 0.05, the Bonferroni correction was applied (level of significance 0.016). The effect size of the parameter was calculated ((the mean of the subjects minus the mean of the matched controls) divided by standard deviation of the two groups). According to Cohen, 0.20 indicates a small effect size, 0.50 indicates a medium effect size and 0.80 indicates a large effect size. RESULTS: Comparison between patients and matched controls: the means of global gain, of gain for the movements to the left and of gain for the movements to the right did not differ significantly between patients and their matched controls. The size effects are 0.31 for the global gain, 0.20 for the movements to the left and 0.41 for the movements to the right. The frequencies of total saccades, catch-up saccades, back-up saccades, anticipatory saccades and square-wave-jerks did not differ significantly between patients and their controls. The size effects for those parameters were 0.09, 0.03, 0.00, 0.39 and 0.63 respectively. Comparison between parents and matched controls: the means of global gain, of gain for the movements to the left and of gain for the movements to the right did not differ significantly between the two groups. The size effects for those parameters were 0.00, 0.05 and 0.17 respectively. The frequency of total saccades did not differ significantly between the groups whereas the size effect was 0.63. The frequency of catch-up saccades was significantly more important in parents than in controls (p = 0.006) and the size effect was 0.80. The other saccadic parameters did not differ significantly between groups, their size effects were 0.24 for the back-up saccades, 0.21 for the anticipatory saccades and 0.00 for the square-wave-jerks. Whereas the gain of the patients had a tendency to be lower than the gain of their controls, no significant difference was observed between patients and their controls. Only a size effect of 0.63 for the frequency of square-wave-jerks was obtained. This large effect size suggests that the difference between patients and controls might be significant in a larger sample. The catch-up saccades frequency between parents and controls was significant. The differences between our study and the previous studies could be due to several factors. The paradigms used were different between the studies and our sample was small (only 15 patients and 19 relatives). Moreover, some patients in the previous studies were treated by lithium, drug well known to modify ocular pursuit and, finally the relatives in the other studies were 10 years older than ours and age is known to alter ocular pursuit. Since an impairment of the smooth pursuit was observed in the relatives of schizophrenic patients but not in the probands, this study does not support the hypothesis that eye-tracking disorders could be considered as a marker of vulnerability of schizophrenia.

Impaired inhibition after total sleep deprivation using an antisaccade task when controlling for circadian modulation of performance.

OBJECTIVE: Sleep deprivation affects several cognitive functions subserved by the prefrontal cortex. Conflicting results have, nonetheless, been reported for inhibitory function, which could be explained by methodological bias. The present study aimed to assess the effects of sleep deprivation on response inhibition using a particularly suitable inhibition test, the antisaccade, while controlling for circadian influences on performance. For this purpose, testing was conducted at: (1) the same time of day in both the control and sleep deprivation conditions; and (2) at a time of day when inhibitory performance has been found not to be at its lowest level. Two other neuropsychological tasks (go no-go and incompatibility) were used for comparison. METHODS: Twelve healthy young participants performed the three tasks in the early afternoon after a normal night and after a total sleep deprivation (TSD) night in a study with a balanced, crossover design. RESULTS: TSD significantly impaired the error rate, the latency, and the intra-individual coefficient of variation of latency in the antisaccade task. None of these parameters were affected in the two neuropsychological tasks. CONCLUSIONS: When circadian modulation of performance is controlled, TSD impairs inhibition assessed by an antisaccade test. This result emphasizes that it is crucial to control for circadian effects when assessing cognitive performance in TSD studies since the time of testing may reveal or mask cognitive and behavioral impairments. The discrepant findings obtained with the go no-go and incompatibility tests are probably explained by the specific task demands and differences in recruitment of prefrontal regions.