The computational pharmacology of oculomotion.

Many physiological and pathological changes in brain function manifest in eye-movement control. As such, assessment of oculomotion is an invaluable part of a clinical examination and affords a non-invasive window on several key aspects of neuronal computation. While oculomotion is often used to detect deficits of the sort associated with vascular or neoplastic events; subtler (e.g. pharmacological) effects on neuronal processing also induce oculomotor changes. We have previously framed oculomotor control as part of active vision, namely, a process of inference comprising two distinct but related challenges. The first is inferring where to look, and the second is inferring how to implement the selected action. In this paper, we draw from recent theoretical work on the neuromodulatory control of active inference. This allows us to simulate the sort of changes we would expect in oculomotor behaviour, following pharmacological enhancement or suppression of key neuromodulators-in terms of deciding where to look and the ensuing trajectory of the eye movement itself. We focus upon the influence of cholinergic and GABAergic agents on the speed of saccades, and consider dopaminergic and noradrenergic effects on more complex, memory-guided, behaviour. In principle, a computational approach to understanding the relationship between pharmacology and oculomotor behaviour affords the opportunity to estimate the influence of a given pharmaceutical upon neuronal function, and to use this to optimise therapeutic interventions on an individual basis.

Effects of nicotine on smooth pursuit eye movements in healthy non-smokers.

RATIONALE: The non-selective nicotinic acetylcholine receptor (nAChR) agonist nicotine has been argued to improve attention via enhanced filtering of irrelevant stimuli. Here, we tested this hypothesis in the context of smooth pursuit eye movements (SPEMs), an oculomotor function previously shown to improve with nicotine in some but not all studies. OBJECTIVES: In order to test whether nicotine improves performance particularly when the inhibition of distracting stimuli is required, SPEM was elicited in conditions with or without peripheral distractors. Additionally, different target frequencies were employed in order to parametrically vary general processing demands on the SPEM system. METHODS: Healthy adult non-smokers (N = 18 females, N = 13 males) completed a horizontal sinusoidal SPEM task at different target frequencies (0.2 Hz, 0.4 Hz, 0.6 Hz) in the presence or absence of peripheral distractors in a double-blind, placebo-controlled, cross-over design using a 2 mg nicotine gum. RESULTS: Nicotine increased peak pursuit gain relative to placebo (p < .001), but an interaction with distractor condition (p = .001) indicated that this effect was most pronounced in the presence of distractors. Catch-up saccade frequency was reduced by nicotine (p = .01), particularly at higher target frequencies (two-way interaction, p = .04). However, a three-way interaction (p = .006) indicated that the reduction with nicotine was strongest at the highest target frequency (0.6 Hz) only without distractors, whereas in the presence of distractors, it was strongest at 0.4-Hz target frequency. There were no effects of nicotine on subjective state measures. CONCLUSIONS: Together, these findings support a role of both distractor inhibition and general processing load in the effects of nicotine on smooth pursuit.

Caffeine increases the velocity of rapid eye movements in unfatigued humans.

BACKGROUND: Caffeine is a widely used dietary stimulant that can reverse the effects of fatigue on cognitive, motor and oculomotor function. However, few studies have examined the effect of caffeine on the oculomotor system when homeostasis has not been disrupted by physical fatigue. This study examined the influence of a moderate dose of caffeine on oculomotor control and visual perception in participants who were not fatigued. METHODS: Within a placebo-controlled crossover design, 13 healthy adults ingested caffeine (5 mg·kg-1 body mass) and were tested over 3 h. Eye movements, including saccades, smooth pursuit and optokinetic nystagmus, were measured using infrared oculography. RESULTS: Caffeine was associated with higher peak saccade velocities (472 ± 60° s-1) compared to placebo (455 ± 62° s-1). Quick phases of optokinetic nystagmus were also significantly faster with caffeine, whereas pursuit eye movements were unchanged. Non-oculomotor perceptual tasks (global motion and global orientation processing) were unaffected by caffeine. CONCLUSIONS: These results show that oculomotor control is modulated by a moderate dose of caffeine in unfatigued humans. These effects are detectable in the kinematics of rapid eye movements, whereas pursuit eye movements and visual perception are unaffected. Oculomotor functions may be sensitive to changes in central catecholamines mediated via caffeine's action as an adenosine antagonist, even when participants are not fatigued.

Effects of nicotine on response inhibition and interference control.

Nicotine is a cholinergic agonist with known pro-cognitive effects in the domains of alerting and orienting attention. However, its effects on attentional top-down functions such as response inhibition and interference control are less well characterised. Here, we investigated the effects of 7 mg transdermal nicotine on performance on a battery of response inhibition and interference control tasks. A sample of N = 44 healthy adult non-smokers performed antisaccade, stop signal, Stroop, go/no-go, flanker, shape matching and Simon tasks, as well as the attentional network test (ANT) and a continuous performance task (CPT). Nicotine was administered in a within-subjects, double-blind, placebo-controlled design, with order of drug administration counterbalanced. Relative to placebo, nicotine led to significantly shorter reaction times on a prosaccade task and on CPT hits but did not significantly improve inhibitory or interference control performance on any task. Instead, nicotine had a negative influence in increasing the interference effect on the Simon task. Nicotine did not alter inter-individual associations between reaction times on congruent trials and error rates on incongruent trials on any task. Finally, there were effects involving order of drug administration, suggesting practice effects but also beneficial nicotine effects when the compound was administered first. Overall, our findings support previous studies showing positive effects of nicotine on basic attentional functions but do not provide direct evidence for an improvement of top-down cognitive control through acute administration of nicotine at this dose in healthy non-smokers.

Oculomotor Deficits after Chemotherapy in Childhood.

Advances in the diagnosis and treatment of pediatric malignancies have substantially increased the number of childhood cancer survivors. However, reports suggest that some of the chemotherapy agents used for treatment can cross the blood brain barrier which may lead to a host of neurological symptoms including oculomotor dysfunction. Whether chemotherapy at young age causes oculomotor dysfunction later in life is unknown. Oculomotor performance was assessed with traditional and novel methods in 23 adults (mean age 25.3 years, treatment age 10.2 years) treated with chemotherapy for a solid malignant tumor not affecting the central nervous system. Their results were compared to those from 25 healthy, age-matched controls (mean age 25.1 years). Correlation analysis was performed between the subjective symptoms reported by the chemotherapy treated subjects (CTS) and oculomotor performance. In CTS, the temporal control of the smooth pursuit velocity (velocity accuracy) was markedly poorer (p<0.001) and the saccades had disproportionally shorter amplitude than normal for the associated saccade peak velocity (main sequence) (p = 0.004), whereas smooth pursuit and saccade onset times were shorter (p = 0.004) in CTS compared with controls. The CTS treated before 12 years of age manifested more severe oculomotor deficits. CTS frequently reported subjective symptoms of visual disturbances (70%), unsteadiness, light-headedness and that things around them were spinning or moving (87%). Several subjective symptoms were significantly related to deficits in oculomotor performance. To conclude, chemotherapy in childhood or adolescence can result in severe oculomotor dysfunctions in adulthood. The revealed oculomotor dysfunctions were significantly related to the subjects' self-perception of visual disturbances, dizziness, light-headedness and sensing unsteadiness. Assessments of oculomotor function may, thus, offer an objective method to track and rate the level of neurological complications following chemotherapy.

GABAergic modulation in central sensitization in humans: a randomized placebo-controlled pharmacokinetic-pharmacodynamic study comparing clobazam with clonazepam in healthy volunteers.

Positive allosteric modulators of GABAA receptors (GAMs) acting at specific subtypes of GABAA receptors effectively restore compromised spinal pain control in rodents. Studies addressing a similar antihyperalgesic effect in humans are sparse and are hampered by sedative effects of nonselective GAMs available for use in humans. We present results from a randomized controlled double-blind crossover study in 25 healthy volunteers, which addressed potential antihyperalgesic actions of clobazam (CBZ) and clonazepam (CLN) at mildly sedating equianticonvulsive doses. Clobazam was chosen because of its relatively low sedative properties and CLN because of its use in neuropathic pain. Tolterodine (TLT) was used as an active placebo. The primary outcome parameter was a change in the area of cutaneous UVB irradiation-induced secondary hyperalgesia (ASH), which was monitored for 8 hours after drug application. Sedative effects were assessed in parallel to antihyperalgesia. Compared with TLT, recovery from hyperalgesia was significantly faster in the CBZ and CLN groups (P = 0.009). At the time point of maximum effect, the rate of recovery from hyperalgesia was accelerated by CBZ and CLN, relative to placebo by 15.7% (95% confidence interval [CI] 0.8-30.5), P = 0.040, and 28.6% (95% CI 4.5-52.6), P = 0.022, respectively. Active compounds induced stronger sedation than placebo, but these differences disappeared 8 hours after drug application. We demonstrate here that GAMs effectively reduce central sensitization in healthy volunteers. These results provide proof-of-principle evidence supporting efficacy of GAMs as antihyperalgesic agents in humans and should stimulate further research on compounds with improved subtype specificity.

Deviant smooth pursuit in preschool children exposed prenatally to methadone or buprenorphine and tobacco affects integrative visuomotor capabilities.

BACKGROUND AND AIMS: Although an increasing number of children are born to mothers in opioid maintenance therapy (OMT), little is known about the long-term effects of these opioids. Previous studies suggest an association between prenatal OMT exposure and difficulties in eye movement control. Also, the effects of tobacco smoking on eye movements have been reported. The present study examined the influence of eye movements, i.e. smooth pursuit, on visuomotor capabilities in children of smoking mothers in OMT. DESIGN: The study comprised a 2 (OMT versus contrast group) × 2 (slow versus fast smooth pursuit) between-subject factorial design. SETTING: The cognitive developmental research unit at the University of Oslo, Norway. PARTICIPANTS: Participants were 26 4-year-old children of tobacco-smoking women in OMT and 23 non-exposed 4-year-old children, with non-smoking mothers, matched by gender and age. MEASUREMENT: Eye movements and smooth pursuit were recorded using a Tobii 1750 eyetracker. Visuomotor functions were examined by Bender test. FINDINGS: The OMT group tracked slowly moving objects with smooth pursuit in a similar manner to their non-exposed peers. When fast smooth pursuit was measured, the OMT group of children tracked the object more slowly than the contrast group, P = 0.02, ηp(2) = 0.11. A regression analysis showed that fast smooth pursuit predicted children's performance on a visuomotor task, R(2) = 0.37. CONCLUSION: Impaired eye-tracking skills in 4-year-old children exposed to methadone or buprenorphine and tobacco prenatally could inhibit the development of some cognitive functions in later life.

Effects of risperidone, amisulpride and nicotine on eye movement control and their modulation by schizotypy.

RATIONALE: The increasing demand to develop more efficient compounds to treat cognitive impairments in schizophrenia has led to the development of experimental model systems. One such model system combines the study of surrogate populations expressing high levels of schizotypy with oculomotor biomarkers. OBJECTIVES: We aimed (1) to replicate oculomotor deficits in a psychometric schizotypy sample and (2) to investigate whether the expected deficits can be remedied by compounds shown to ameliorate impairments in schizophrenia. METHODS: In this randomized double-blind, placebo-controlled study 233 healthy participants performed prosaccade (PS), antisaccade (AS) and smooth pursuit eye movement (SPEM) tasks after being randomly assigned to one of four drug groups (nicotine, risperidone, amisulpride, placebo). Participants were classified into medium- and high-schizotypy groups based on their scores on the Schizotypal Personality Questionnaire (SPQ, Raine (Schizophr Bull 17:555-564, 1991)). RESULTS: AS error rate showed a main effect of Drug (p < 0.01), with nicotine improving performance, and a Drug by Schizotypy interaction (p = 0.04), indicating higher error rates in medium schizotypes (p = 0.01) but not high schizotypes under risperidone compared to placebo. High schizotypes had higher error rates than medium schizotypes under placebo (p = 0.03). There was a main effect of Drug for saccadic peak velocity and SPEM velocity gain (both p ≤ 0.01) indicating impaired performance with risperidone. CONCLUSIONS: We replicate the observation of AS impairments in high schizotypy under placebo and show that nicotine enhances performance irrespective of group status. Caution should be exerted in applying this model as no beneficial effects of antipsychotics were seen in high schizotypes.

Nicotine enhances antisaccade performance in schizophrenia patients and healthy controls.

Nicotine has been proposed to be a cognitive enhancer, particularly in schizophrenia patients. So far, the published studies of nicotine effects on antisaccade performance in schizophrenia patients only tested participants who were deprived smokers. Thus, we aimed to test both smoking and non-smoking patients as well as healthy controls in order to extend previous findings. Moreover, we employed a paradigm using standard and delayed trials. We hypothesized that, if nicotine is a genuine cognitive enhancer, its administration would improve antisaccade performance both in smoking and non-smoking participants. A total of 22 patients with schizophrenia (12 smokers and 10 non-smokers) and 26 controls (14 smokers and 12 non-smokers) completed the study. The effects of a nicotine patch (14 mg for smokers, 7 mg for non-smokers) on antisaccade performance were tested in a randomized, double-blind, placebo-controlled, cross-over trial. Schizophrenia patients made significantly more antisaccade errors than controls (p = 0.03). Both patients and controls made fewer antisaccade errors in the delayed trials than in the standard trials (p < 0.0001). Nicotine significantly reduced antisaccade error rate in the standard trials, but not in the delayed trials (p = 0.02). Smoking status did not influence the nicotine effect on antisaccade error rate (p = 0.10) indicating an equal procognitive effect of nicotine in smokers and non-smokers. Overall the present findings indicate that beneficial effects of nicotine on antisaccade performance are not confined to smoking schizophrenia patients. Instead, the findings likely represent genuine nicotine-induced enhancement of cognitive performance.

Nicotine differentially modulates antisaccade eye-gaze away from emotional stimuli in nonsmokers stratified by pre-task baseline performance.

RATIONALE AND OBJECTIVE: Studies indicate that nicotine enhances some aspects of attention and executive functioning and attenuates the attentional salience of emotionally negative distractors. The purpose of this study was to assess whether nicotine can enhance executive control over prepotent responses in emotional contexts in nonsmokers and whether such enhancement is greater in individuals with low baseline performance (BP). METHODS: The antisaccade task (AST) measures the inhibition of the tendency to glance in the direction of the onset of a visual stimulus and thus is an index of control over prepotent responses. Ten male and 14 female nonsmokers wore nicotine and placebo patches on counterbalanced days that included emotional picture primes and targets. RESULTS: There were significant beneficial effects of nicotine on antisaccade reaction time (RT). These beneficial effects occurred in individuals with poor and average BP, but not in high baseline performers. In slow baseline RT individuals, nicotine reduced RTs associated with negative targets in the left visual field (VF) and reduced RTs associated with positive and neutral targets in the right VF. In contrast, in the average baseline group, nicotine reduced RTs for positive targets in both VFs and neutral targets in the left VF. CONCLUSIONS: The results suggest that nicotine may produce its effects by enhancing executive functions and that the differential effects as a function of VF, target emotion, and group may also reflect lateralized differences in the effects of nicotine on brain reactivity to emotional stimuli.

Nicotine differentially modulates antisaccade performance in healthy male non-smoking volunteers stratified for low and high accuracy.

RATIONALE: Nicotinergic agents are currently examined as possible pro-cognitive drugs for a variety of clinical conditions marked by cognitive deficits, such as attention deficit hyperactivity disorder (ADHD) or schizophrenia. The response to acute nicotine is heterogeneous across subjects and samples; however, only a few reliable predictors of response have been identified. OBJECTIVES: We tested the hypothesis that baseline performance level in cognitive control may be a predictor of the cognitive effects of nicotine. METHODS: We tested 28 healthy Caucasian, male, non-smoking volunteers with the antisaccade task, an oculomotor measure of cognitive control. Participants were given a 7-mg nicotine patch in a double-blind, placebo-controlled, counterbalanced, within-subjects design. Subjects were stratified into high and low performers based on their antisaccade error rate in the placebo condition (median split). RESULTS: Nicotine tended to reduce response time variability of prosaccade latency (p = 0.06). There was no main effect of nicotine on antisaccade error rate (p = 0.31). However, nicotine significantly reduced antisaccade error rate in the low-accuracy probands while leaving performance of the high-accuracy probands unaffected (interaction, p < 0.05). Furthermore, we found a nicotine-induced reduction of response time variability of antisaccade latency at one target location in the low-performing group (interaction, p < 0.05). CONCLUSIONS: The present results demonstrate the importance of baseline performance differences for the effectiveness of pharmacological enhancement of cognitive control. More generally, the results suggest that stimulation of the nicotinic acetylcholine receptor system might be an effective way of improving cognition in people with poor cognitive performance, such as patients with ADHD or schizophrenia.

Electrophysiological evidence of the effect of natural polyphenols upon the human higher brain functions.

OBJECTIVE: Several natural polyphenols exert effects upon the cardiovascular as well as nervous system. In vitro and animal studies suggest that polyphenols may potentially affect the human cognitive function. The aim was to study the effect of Provinols™, the polyphenolic compounds isolated from red wine, upon the human higher brain functions. MATERIAL AND METHODS: The accuracy of space memory was assessed by means of visually-guided and memory-guided saccadic eye movements. The EEG and blood pressure were registered also. The healthy undergraduates served as subjects. They were divided into the control, placebo and Provinols™ groups. The amplitudes of saccades, EEG spectral density, evoked potentials time-locked to saccadic onset and blood pressure were analyzed in control condition and 2 hours later, after administration of placebo, Provinols™ (4 mg/kg of body weight) or nothing. RESULTS: After the Provinols™ administration the memory-guided saccades were significantly more accurate and the significant decrease in the slow EEG bands, alpha power mainly, was registered over the broad regions of temporo-parietal cortex. No changes in saccadic eye movement related potentials as well as in blood pressure were found after the single dose Provinols™ administration. CONCLUSIONS: Even a single dose of the Provinols™ was able to affect positively the space memory for limited time duration. The improvement in space memory function and/or the positive role of attentional mechanisms may be taken into account mainly. More sensitive analysis of the particular participation of attentional and memory components demands the further study.

Effect of nicotine on saccadic eye movement latencies in non-smokers.

OBJECTIVE: Recently, saccadic eye movement tasks have been used to assess the effects of nicotine on higher cognitive processes, including inhibitory control. Saccadic task switching methods suggest that there is prolonged inhibition of the saccadic eye movement system following antisaccade trials. The objective of this research was to examine effects of nicotine on inhibition using saccadic task switching paradigms. METHODS: Nicotine and placebo lozenges were administered on separate days to 40 non-smokers who performed prosaccade and antisaccade tasks. In addition, participants performed a series of trials in which prosaccade and antisaccade tasks were switched. Eye movement latencies were recorded. RESULTS: Participants responded significantly faster for the nicotine condition than for the placebo condition. A switch benefit was observed for only placebo antisaccade trials, in that latencies of repetition trials were significantly longer than those of switch trials. In addition, an analysis of the repetition trials showed an interaction between saccade type and sequence position for the placebo condition, but not the nicotine condition. CONCLUSION: Inhibition persists after antisaccade trials in a switching paradigm, but that the duration of this inhibition is reduced by nicotine.

Allopregnanolone serum concentrations and neurosteroid sensitivity during withdrawal from postmenopausal hormone therapy.

BACKGROUND: We have previously compared the pharmacodynamic response to a neuroactive steroid, pregnanolone, before and during sequential treatment with estradiol-only (E2-only) and estradiol together with progesterone (E2 + P) in postmenopausal women. The aim of the present study was to evaluate the pharmacodynamic response to pregnanolone during withdrawal from E2-only treatment and during withdrawal from treatment with E2 + P. METHOD: Twenty-six postmenopausal women were administered hormone therapy (HT) in a randomized, double blinded, placebo-controlled, crossover study. The women received 2 mg oral estradiol continuously during two 28-day cycles and 800 mg vaginal progesterone or placebo sequentially for the last 14 days of each treatment cycle. The pharmacodynamic response to pregnanolone was assessed during the last week of the last treatment cycle and 48 h after termination of the last treatment cycle (withdrawal) by comparing the effects of intravenous pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) on saccadic eye movements. RESULTS: During E2-only withdrawal the pregnanolone sensitivity was reduced compared with E2-only treatment. Pregnanolone sensitivity remained unaltered between the combined E2 + P treatment regimen and the withdrawal from these steroids. CONCLUSION: The study indicates that withdrawal from E2-only treatment might change neurosteroid sensitivity, whereas the immediate withdrawal from E2 + P results in unchanged neurosteroid sensitivity.

Non-cholinergic modulation of antisaccade performance: a modafinil-nicotine comparison.

INTRODUCTION: The antisaccade task provides a powerful tool with which to investigate the cognitive and neural systems underlying goal-directed behaviour, particularly in situations when the correct behavioural response requires the suppression of a prepotent response. Antisaccade errors (failures to suppress reflexive prosaccades towards sudden-onset targets) are increased in patients with damage to the dorsolateral prefrontal cortex, and in patients with schizophrenia. Nicotine has been found to improve antisaccade performance in patients with schizophrenia and healthy controls. This performance enhancing effect may be due to direct effects on the cholinergic system, but there has been no test of this hypothesis. MATERIALS AND METHODS: In a double blind, double dummy, placebo-controlled design, we compared the effect of nicotine and modafinil, a putative indirect noradrenergic agonist, on antisaccade performance in healthy non-smokers. RESULTS AND DISCUSSION: Both compounds reduced latency for correct antisaccades, although neither reduced antisaccade errors. These findings are discussed with reference to the pharmacological route of performance enhancement on the antisaccade task and current models of antisaccade performance.

A double-blind placebo-controlled experimental study of nicotine: II--Effects on response inhibition and executive functioning.

RATIONALE: Smokers may show abnormal functioning in prefrontal cortex during acute abstinence, reflecting deficient activity in mesocorticolimbic circuitry. Cognitive correlates of this putatively include impaired response inhibition and other aspects of executive functioning. OBJECTIVES: To investigate whether inhibitory control and other executive functions in smokers are impaired during acute abstinence relative to post-nicotine. METHODS: 145 smokers were tested twice after overnight abstinence-once after nicotine and once after placebo lozenges (order counterbalanced, double-blind)-on an antisaccade task, a continuous performance task (CPT), a delayed response spatial working memory task and a verbal fluency test. RESULTS: Compared with placebo, nicotine was associated with better inhibitory control on the antisaccade task and fewer impulsive responses to filler stimuli (motor errors) on the CPT; at the first assessment only, nicotine also reduced impulsive responses to 'catch' stimuli on the CPT. However, it did not affect CPT response bias (an index of impulsive vs cautious decision-making), spatial working memory, or verbal fluency. CONCLUSIONS: Smoking abstinence appears to be associated with a difficulty in inhibiting prepotent motor responses, and with nicotine to attenuate this difficulty. However, more 'cognitive' forms of inhibitory control (e.g. decision-making) and the other aspects of executive function tested here appear to be unaffected.

Oral progesterone decreases saccadic eye velocity and increases sedation in women.

The aim of this study was to investigate the neurophysiological and behavioural effects of a single dose of progesterone in women. Allopregnanolone is a metabolite of progesterone and a potent positive modulator of the GABA(A) receptor and produces sedative and anxiolytic effects. This study was designed to examine the effect of oral progesterone and the metabolite allopregnanolone in women. Women (n=15) in their follicular phase received oral progesterone (400mg) or placebo. Dependent measures included plasma levels of progesterone and allopregnanolone, saccadic eye velocity (SEV), subjective ratings (visual analogue scales), and reaction time. Administration of progesterone decreased SEV and increased sedation. This effect is probably due to enhanced GABA activity.

The antisaccade task as an index of sustained goal activation in working memory: modulation by nicotine.

INTRODUCTION: The antisaccade task provides a laboratory analogue of situations in which execution of the correct behavioural response requires the suppression of a more prepotent or habitual response. Errors (failures to inhibit a reflexive prosaccade towards a sudden onset target) are significantly increased in patients with damage to the dorsolateral prefrontal cortex and patients with schizophrenia. Recent models of antisaccade performance suggest that errors are more likely to occur when the intention to initiate an antisaccade is insufficiently activated within working memory. Nicotine has been shown to enhance specific working memory processes in healthy adults. MATERIALS AND METHODS: We explored the effect of nicotine on antisaccade performance in a large sample (N = 44) of young adult smokers. Minimally abstinent participants attended two test sessions and were asked to smoke one of their own cigarettes between baseline and retest during one session only. RESULTS AND CONCLUSION: Nicotine reduced antisaccade errors and correct antisaccade latencies if delivered before optimum performance levels are achieved, suggesting that nicotine supports the activation of intentions in working memory during task performance. The implications of this research for current theoretical accounts of antisaccade performance, and for interpreting the increased rate of antisaccade errors found in some psychiatric patient groups are discussed.

Propofol-remifentanil-based anaesthesia vs. sevoflurane-fentanyl-based anaesthesia for immediate postoperative ophthalmic evaluation following strabismus surgery.

BACKGROUND AND OBJECTIVE: Following strabismus surgery, immediate postoperative ophthalmic evaluation may be desired. Thus, an anaesthetic technique allowing rapid recovery of ocular motility is required. Saccadic eye movements is a biophysical monitor of ocular motility and may be used to assess recovery from anaesthesia. The aim of this study is to compare the time to the recovery of saccadic eye movements in patients, following one of two anaesthetic techniques: Propofol-remifentanil-based anaesthesia vs. sevoflurane-fentanyl-based anaesthesia. METHODS: Fifty adult patients undergoing strabismus surgery were randomly assigned to one of two groups: patients in Group R received induction and maintenance of anaesthesia with propofol and remifentanil, while patients in Group S received induction of anaesthesia with propofol and fentanyl and maintenance of anaesthesia with sevoflurane. Recovery from anaesthesia was measured from the time all anaesthetics were turned off and was assessed every 2 min. Recovery time was attained when patients were able to generate brisk saccadic eye movements. At recovery time, the ophthalmic evaluation was started. RESULTS: The mean recovery time of saccadic eye movements was significantly shorter in the Group R when compared to the Group S (12.1 +/- 4.3 min vs. 21.5 +/- 4.7 min, respectively, P < 0.0001). More patients in Group S experienced nausea and vomiting postoperatively as compared to Group R (9/25 vs. 2/25, respectively, P = 0.037). CONCLUSIONS: Propofol-remifentanil-based anaesthesia may be a useful technique in strabismus surgery when immediate postoperative ophthalmic evaluation is desired. When compared to sevoflurane maintenance of anaesthesia, it allows for a more rapid recovery from anaesthesia as judged by recovery of saccadic eye movements and a decreased incidence of postoperative nausea and vomiting.

Acute effects of nicotine on visual search tasks in young adult smokers.

RATIONALE: Nicotine is known to improve performance on tests involving sustained attention and recent research suggests that nicotine may also improve performance on tests involving the strategic allocation of attention and working memory. OBJECTIVES: We used measures of accuracy and response latency combined with eye-tracking techniques to examine the effects of nicotine on visual search tasks. METHODS: In experiment 1 smokers and non-smokers performed pop-out and serial search tasks. In experiment 2, we used a within-subject design and a more demanding search task for multiple targets. In both studies, 2-h abstinent smokers were asked to smoke one of their own cigarettes between baseline and tests. RESULTS: In experiment 1, pop-out search times were faster after nicotine, without a loss in accuracy. Similar effects were observed for serial searches, but these were significant only at a trend level. In experiment 2, nicotine facilitated a strategic change in eye movements resulting in a higher proportion of fixations on target letters. If the cigarette was smoked on the first trial (when the task was novel), nicotine additionally reduced the total number of fixations and re-fixations on all letters in the display. CONCLUSIONS: Nicotine improves visual search performance by speeding up search time and enabling a better focus of attention on task relevant items. This appears to reflect more efficient inhibition of eye movements towards task irrelevant stimuli, and better active maintenance of task goals. When the task is novel, and therefore more difficult, nicotine lessens the need to re-fixate previously seen letters, suggesting an improvement in working memory.