Effects of classic antiseizure drugs on seizure activity and anxiety-like behavior in adult zebrafish.

The zebrafish is extensively used as a model organism for studying several disorders of the central nervous system (CNS), including epilepsy. Some antiseizure drugs (ASDs) have been shown to produce discrepant results in larvae and adults zebrafish, therefore, their anticonvulsant efficacy in subsequent stages of the pentylenetetrazole (PTZ)-induced seizures should be more precisely characterized. The purpose of this study was to investigate behavioral effects of five classic ASDs: valproate (VPA), phenytoin (PHT), carbamazepine (CBZ), diazepam (DZP), and phenobarbital (PB) administered intraperitoneally (i.p.) in the PTZ-induced seizure test in adult zebrafish. We determined the time of maximal effect and the dose-response relationship of the studied ASDs. Furthermore, we assessed changes in the locomotor activity and the anxiety-like behavior in the color preference test. Moreover, drug concentrations in zebrafish homogenates were examined. VPA, DZP, and PB significantly increased the seizure latency at three subsequent stages of seizures (SI-SIII). PHT produced the anticonvulsant-like effect at SI and SII, while CBZ was effective at SII and SIII. Only DZP decreased zebrafish locomotor activity. A strong anxiolytic-like effect was observed after administration of PHT and PB. A weak anxiolytic-like effect occurred after treatment with VPA and DZP. The HPLC analysis showed the average concentrations of the studied ASDs in the fish body during the maximum anticonvulsant activity of each drug. Our results confirm the advantages of using zebrafish with the mature CNS over larval models and its utility to investigate some neuropharmacological properties of the tested drugs.

Processing speed can monitor stimulant-medication effects in adults with attention deficit disorder with hyperactivity.

BACKGROUND: Treatment responses to methylphenidate by adults with ADHD are generally monitored against DSM-IV/DSM-V symptomatology, rating scales or interviews during reviews. AIMS: To evaluate the use of single- and dual-dimension processing-speed and efficiency measures to monitor the effects of pharmacological treatment with methylphenidate after a short period off medication. METHODS: A Quick Test of Cognitive Speed (AQT) monitored the effects of immediate-release methylphenidate in 40 previously diagnosed and medicated adults with ADHD. Processing speed was evaluated with prior prescription medication, without medication after a 2-day period off ADHD medication, and with low-dose (10/20 mg) and high-dose (20/40 mg) methylphenidate hydrochloride (Medikinet IR). RESULTS: Thirty-three participants responded to the experimental treatments. One-way ANOVA with post-hoc analysis (Scheffe) indicated significant main effects for single dimension colour and form and dual-dimension colour-form naming. Post-hoc analysis indicated statistical differences between the no- and high-dose medication conditions for colour and form, measures of perceptual speed. For colour-form naming, a measure of cognitive speed, there was a significant difference between no- and low-dose medication and between no- and high-dose medications, but not between low- and high-dose medications. CONCLUSIONS: Results indicated that the AQT tests effectively monitored incremental effects of the methylphenidate dose on processing speed after a 2-day period off medication. Thus, perceptual (colour and form) and cognitive speed (two-dimensional colour-form naming) and processing efficiency (lowered shift costs) increased measurably with high-dose medication. These preliminary findings warrant validation with added measures of associated behavioural and cognitive changes.

Fabrication and Validation of Gyro-Dot-Optomotor Response Device using Gold Fish to Study Drugs Affecting Visual Perception.

An appropriate model to predict the effect of xenobiotics on the vision perception in neuropsychoharmacological studies is of great importance in drug development and toxicity studies. The present study valuated the effect of CNS stimulant, depressant and therapeutic agents known to have ocular toxicity on ptomotor response (OMR) using goldfish in a newly developed device. A digital light processing aided gyrating poly-chromatic dotted pattern-OMR (Gyro-dot-OMR) analyzer was developed and standardized for this study in our laboratory. Goldfishes were exposed to varying concentrations of caffeine and pentobarbitone sodium to evaluate the effect of CNS stimulation and depression on OMR in white light. Ethambutol induced ocular toxicity was evaluated by intravitreal injection into both eyes of goldfishes. They were subjected for polychromatic Gyro-dot-OMR in both clock and anticlockwise directions. At the low concentration (5, 10 and 20 ng/mL) caffeine exposed animals showed significant (p<0.05) stimulant effect and the EC(50) of caffeine in goldfish was found to be 4.806 ng/mL. In contrast, pentbbarbitone sodium treated fishes showed significant (p<0.05) depressant effect with increasing the concentration. Ethambutol toxicity was reflected by the color iscrimination in the Gyro-dot-OMR pattern. For the first time, this model proved the possibility of running Irwin profile test on goldfish using Gyro-dot-OMR. This model successfully predicted ethambutol induced toxicity with poor discrimination of red-green color. This model can be used for predicting toxicity of drugs affecting vision perception.

Directional and color preference in adult zebrafish: Implications in behavioral and learning assays in neurotoxicology studies.

The zebrafish (Danio rerio) is a useful vertebrate model organism for neurological studies. While a number of behavior and learning assays are recently reported in the literature for zebrafish, many of these assays are still being refined. The initial purpose of this study was to apply a published T-maze assay for adult zebrafish that measures how quickly an organism can discriminate between different color stimuli after receiving reinforcement to measure learning in a study investigating the later life impacts of developmental Pb exposure. The original results were inconclusive as the control group showed a directional and color preference. To assess directional preference further, a three-chambered testing apparatus was constructed and rotated in several directions. The directional preference observed in males was alleviated by rotating the arms pointing west and east. In addition, color preference was investigated using all combinations of five different colors (orange, yellow, green, blue and purple). With directional preference alleviated results showed that both male and female zebrafish preferred colors of shorter wavelengths. An additional experiment tested changes in color preference due to developmental exposure to Pb in adult male zebrafish. Results revealed that Pb-exposed males gained and lost certain color preferences compared to control males and the preference for short wavelengths was decreased. Overall, these results show that consideration and pretesting should be completed before applying behavioral and learning assays involving adult zebrafish to avoid innate preferences and confounding changes in neurotoxicology studies and that developmental Pb exposure alters color preferences in adult male zebrafish.

Influence of gender, anxiety and depression symptoms, and use of oral contraceptive in color perception.

OBJECTIVE: The color is a psychophysical phenomenon, and much has been studied about its physical components. However, the psychological part is poorly investigated, except for the difference between genders in the literature shows that more men are color deficient than women. Dental students are trained to better understand the differences in color, so we became interested in studying whether psychological variables such as anxiety and depression and use of hormonal contraceptives may interfere with this ability. The aim of this in vitro study was to investigate if factors, such as, hormonal contraceptive use, depressive symptoms, anxiety and quality of life, influence on the ability of color discrimination of dental school students. MATERIALS AND METHODS: Sixty-one subjects participated and the following instruments apply: (1) test that consists in the observation of a set of 25 labels (Pantones) with values of known colors, (2) scales of depression, anxiety, and quality of life assessments, and (3) Ishihara test. RESULTS: No difference was observed between genders as color perception (p = 0.868). Symptoms of anxiety and depression were significantly more frequent in the female population that showed worse quality of life (p < 0.000) but did not interfere with color perception. Women using hormonal contraceptives had lower color perception than men (p = 0.04). CONCLUSION: No difference between the genders in the perception of colors was observed, contrary to common sense that women discriminate more colors than men, but women using hormonal contraceptives showed more difficulty in color perception. CLINICAL SIGNIFICANCE: The ability to understand and distinguish color differences is extremely important in clinical dentistry. There could be differences in color perception between men and women that would influence clinical performance.

Ocular findings in breast cancer patients using tamoxifen.

AIM: To examine ocular findings of breast cancer patients using tamoxifen. METHODS: The records of 79 consecutive breast cancer patients were examined, retrospectively. Female patients who had previously been diagnosed to have breast cancer with either stage I, II, or III disease, and were older than 25 years of age were included in the study. Results of the ophthalmic examination, color discrimination, and contrast sensitivity tests were recorded. Short wavelength automated perimetry (SWAP) sensitivity values were obtained, and average sensitivity values of test points at 5°, 9°, 15°, and 21° from the fixation were calculated. RESULTS: Forty-nine of the patients had received 20 mg daily dose of tamoxifen therapy (tamoxifen group), while remaining 30 patients had not used tamoxifen (control group). Anterior and posterior segment examination revealed no pathologic findings in both groups. Two patients (5%) in the tamoxifen group had diffuse color loss, while none did in the control group (p = 0.523). Statistically significant differences were not detected between two groups when square roots of total error in color vision, red-green, and blue-yellow partial error scores were compared. Contrast sensitivity values were similar in both groups. Average mean deviation (MD) and average sensitivity values of test points at each 4° were statistically significantly lower in the tamoxifen group than the control group (p = 0.002, p = 0.001, p < 0.001 and p < 0.001 for right eye; p = 0.002, p= 0.001, p < 0.001 and p < 0.001 for left eye). Strong correlation was detected between MD, and duration (r = -0.832 and r = -0.842 for right and left eyes, respectively) and cumulative dose of tamoxifen use (r = -0.864 and r = -0.854 for right and left eyes, respectively). CONCLUSION: Clinically significant ocular toxicity is not frequently encountered in breast cancer patients, however, SWAP changes may occur early after tamoxifen utilization.

Dopamine precursor depletion impairs timing in healthy volunteers by attenuating activity in putamen and supplementary motor area.

Neuropsychological investigations of patients with Parkinson's disease, schizophrenia, or attention deficit disorder converge with psychopharmacological studies in animals and healthy volunteers to implicate dopamine (DA) pathways in timing. In parallel, single-cell recording and functional neuroimaging studies have highlighted the importance of basal ganglia, prefrontal cortex, and supplementary motor area (SMA) for timing. In a placebo-controlled, within-subject design, we combined event-related functional magnetic resonance imaging with a DA manipulation (acute phenylalanine/tyrosine depletion; APTD) in healthy volunteers to pinpoint the neuroanatomical and functional substrates of the DA modulation of timing. Behaviorally, APTD selectively impaired accuracy of perceptual timing, with no effect on performance of a color-control task matched for difficulty, working memory (WM), and attentional demands. Neurally, APTD attenuated timing-specific activity in the putamen and SMA. Notably, APTD-induced decreases in brain activity were directly correlated to APTD-induced impairments in timing performance. Moreover, APTD modulated timing-specific activity selectively during initial storage of the sample duration, but had no effect during its subsequent retrieval or comparison to a probe. Our results do not simply reflect DA modulation of WM since the color task controlled for the WM updating process necessary for timing of durations in the seconds range. Moreover, preliminary evidence indicated APTD effects on putamen and SMA were greater for subsecond (540 ms) than suprasecond (1080 ms) durations, when WM demands would actually be lower. Instead, we show for the first time in healthy humans that DA manipulation perturbs timing by attenuating the activity in putamen and SMA that mediates initial storage of temporal information into WM.

Early stage development of the glycine-1 re-uptake inhibitor SCH 900435: central nervous system effects compared with placebo in healthy men.

AIMS: To report the first three studies with SCH 900435, a selective glycine-1 re-uptake inhibitor in development for treating schizophrenia, using systematic evaluations of pharmacodynamics to understand the observed effects. METHODS: Three double-blind, placebo-controlled studies (single, visual effect and multiple dose) were performed. In the single and multiple dose study SCH 900435 (0.5-30 mg) was given to healthy males and frequent pharmacokinetic and pharmacodynamic measurements were performed. The visual effects study incorporated visual electrophysiological measures of macular, retinal and intracranial visual pathway function. RESULTS: In the single dose study (highest difference, 95% CI, P) increases in smooth pursuit eye movements (8, 12 mg (-6.09, 10.14, -2.04, 0.013), 30 mg), pupil : iris ratio (20 and 30 mg (-0.065, 0.09, -0.04, <0.0001)), VAS colour perception (30 mg (-9.48, 13.05, -5.91, <0.0001)) and changes in spontaneous reports of visual disturbance were found, while FSH (8 mg (0.42, 0.18, 0.66, 0.0015), 12, 20 mg), LH (8-30 mg (1.35, 0.65, 2.05, 0.0003)) and EEG alpha2 activity decreased (12, 20, 30 mg (0.27, 0.14, 0.41, 0.0002)). A subsequent dedicated visual effects study demonstrated that visual effects were transient without underlying electrophysiological changes. This provided enough safety information for starting a multiple ascending dose study, showing less visual symptoms after twice daily dosing and titration, possibly due to tolerance. CONCLUSIONS: Several central nervous system (CNS) effects and gonadotropic changes resulted from administration of 8 mg and higher, providing evidence for CNS penetration and pharmacological activity of SCH 900435. Antipsychotic activity in patients, specificity of the reported effects for this drug class and possible tolerance to visual symptoms remain to be established.

Simvastatin improves final visual outcome in acute optic neuritis: a randomized study.

BACKGROUND: In recent years, small-scale clinical trials have indicated that statins or 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors exert pleiotropic immunomodulatory effects, with potential therapeutic implications in multiple sclerosis (MS). OBJECTIVE: To investigate whether simvastatin treatment (80 mg daily for 6 months) in patients with optic neuritis (ON) had a beneficial effect on visual outcome and on brain MRI. METHODS: Sixty-four patients with acute ON were randomized to simvastatin treatment (n = 32) or placebo (n = 32) for 6 months. None of the patients had been on immunosuppressive therapy for 6 months prior to inclusion or treated with steroids from symptom onset. Contrast sensitivity (Arden plates), visual acuity, colour perception, visual evoked potentials (VEP)--latency and amplitude, Visual Analogue Scale (VAS) score, and gadolinium enhancing and T2 lesions on brain MRI were evaluated at screening visit, day 14 (except brain MRI), day 90 and day 180. RESULTS: Simvastatin had a beneficial effect on VEP in both latency (p = 0.01) and amplitude (p = 0.01), a borderline effect on the Arden score (p = 0.06) and VAS (p = 0.04), and no effect on brain MRI or on relapse rate between the groups. CONCLUSION: This study provides Class I evidence that simvastatin 80 mg daily is well tolerated and possibly effective in patients with acute ON.

Intravitreal pegaptanib sodium (Macugen®) for treatment of diabetic macular oedema: a morphologic and functional study.

AIMS: To study whether morphologic (foveal thickness, FT) variations of clinically significant macular oedema (CMO) in patients suffering from diabetes following intravitreal pegaptanib sodium (IVP) injection were associated with functional [macular sensitivity (MS) and colour discrimination (CD)] changes. METHODS: A longitudinal, interventional, non-randomized study was performed. FT was assessed by optical coherence tomography (OCT), MS by microperimetry, best-corrected visual acuity (BCVA) by early treatment diabetic retinopathy study charts (ETDRS) and CD by Farnswoth-Munsell test. The treatment protocol consisted of three consecutive injections (0.3 mg/0.05 ml; baseline, week 6 and week 12). Follow-up checks were scheduled at 18, 24, 36 and 48 weeks, after injections. RESULTS: Thirty eyes of 30 patients with clinically significant CMO were included for analysis. After IVP a significant decrease of FT occurred with a mean reduction from baseline of 56.9% (P= 0.0001). An improvement of functional parameters was recorded in all patients (BCVA from 18.2 ± 8.5 letters to 25.5 ± 8.4 letters, P < 0.005, MS from 8.6 ± 2.16 dB to 10.6 ± 2.61 dB, P < 0.001, colour analysis from 376.1 ± 125.6 TES to 116 ± 34.6 TES, P= 0.0001). A statistically significant correlation between FT and BCVA as well as MS and CD was also found. Neither ocular nor systemic adverse events were reported. CONCLUSIONS: Intravitreal pegaptanib significantly reduced FT, with a concomitant improvement of MS and CD. This association emphasizes the efficacy of IVP in the treatment of CMO.

An accessory chromophore in red vision.

In the absence of a red-sensitive visual pigment, some deep-sea fish use a chlorophyll derivative in their green-sensitive rod cells in order to see deep-red light. Here we show that living rods extracted from a salamander can also accumulate an exogenous chlorophyll derivative, chlorin e6, that renders them as sensitive to red light as they are to green. This vision enhancement by an unbleachable chlorophyll derivative might therefore be a general phenomenon in vertebrate photoreception.

Impairment of color vision in aircraft maintenance workers.

PURPOSE: The purpose of the study was to examine possible persisting effects to color vision in a group from the Royal Australian Air Force who had exposure to formulations containing neurotoxins during F-111 fuel tank maintenance, relative to two contemporaneous comparison groups. METHODS: Color vision was tested in 512 exposed personnel, 458 technical-trade comparisons, and 330 non-technical comparisons using the Ishihara test plates and the Lanthony D-15 Desaturated Color disk arrangement test. Participants were excluded if they failed the Ishihara test as this indicates congenital color blindness. From the Lanthony results, the type of color deficient vision (CDV) was diagnosed, and additionally, the Bowman's color confusion index (CCI) was calculated. Regression models were used to examine whether there was an association between color vision deficiencies and F-111 fuel tank maintenance, adjusting for possible confounders. RESULTS: The CCI ranged from 1 to 2.8 (median 1.2, quartiles 1.1, 1.4) in the 2,600 eyes tested. Forty five percent of all participants had blue-yellow CDV in at least one eye. Deficiencies of this nature are caused by environmental exposures. Logistic regression demonstrated statistically significant differences in CCI category in the exposed group versus technical group (odds ratio 1.7: 95% CI 1.3-2.0) and a blue-yellow confusion in the exposed group versus technical group (odds ratio 1.4: 95% CI 1.1-1.7). No differences were observed between the exposed group and the non-technical group. CONCLUSION: The results indicate reduced color discrimination among the exposed subjects compared to one of two control groups. The findings may be due to previous exposure to solvents among the air force personnel.

Propofol dose-dependently increases bite force during sedation.

PURPOSE: The purpose of this study was to investigate the dose-dependent effects of propofol on cognitive function and muscle power as well as vital functions. MATERIALS AND METHODS: Twenty volunteers participated in this study. Each subject underwent 2 experiments in a randomized crossover manner (propofol group and control group). After control data were obtained, propofol at predicted effect site concentrations of 0.4, 0.8, 1.2, 1.6, and 2.0 µg/mL was infused in the propofol group using a target controlled infusion system. Heart rate, noninvasive blood pressure, arterial oxygen saturation, respiratory rate, and bispectral index value were monitored. Observer's assessment of alertness/sedation and the correct answer rate of the Stroop color word test were assessed. Muscle power, grip strength and bite force were measured. RESULTS: In the propofol group, the bispectral index value and observer's assessment of alertness/sedation scale dose-dependently reduced. At the predicted effect site propofol concentration of 2.0 µg/mL, 6 subjects became unconscious. The correct answer rate of Stroop color word test reduced at the predicted effect site propofol concentration of 1.6 and 2.0 µg/mL. Grip strength slightly increased at the predicted effect site propofol concentration of 1.2 µg/mL or less, and bite force dose-dependently increased. At the predicted effect site propofol concentration of 2.0 µg/mL, both muscle powers began to decrease. Bite force dose-dependently increased and reached the maximum at the predicted effect site propofol concentration of 1.6 µg/mL. CONCLUSION: Although the detailed mechanisms are unknown, propofol dose-dependently increases bite force during minimal and moderate sedation.

[Color vision impairment in workers exposed to mercury vapor]. / Zaburzenia widzenia barwnego u pracowników narazonych na dzialanie par rteci.

INTRODUCTION: Acquired reversible dyschromatopsia has been associated with occupational exposure to mercury vapor. Early-detected impairments in color discrimination precede adverse permanent effects of mercury, so they may help to monitor the health of the exposed workers. The aim of this study was to evaluate the color discrimination ability in this group of workers, using Lanthony D-15d test. MATERIAL AND METHODS: Employed in a chloralkali plant, 27 male workers exposed to mercury vapor and 27 healthy white-collar workers (control group) were qualified for the study. To assess color discrimination, the Lanthony 15-Hue desaturated test (Lanthony D-15) was used. In order to investigate quantitative and qualitative results, the Lanthony D-15d scoring software was performed. Urinary mercury was determined using flameless atomic absorption spectrometry. RESULTS: In the workers exposed to mercury vapor, urine mercury concentration was 117.4 +/- 62.6 microg/g creatinine on average compared with 0.279 +/- 0.224 mg/g creatinine in the control group (p < 0.0001). In 18 exposed persons (66.7%), the results of the Lanthony D-15d test showed qualitative changes, which are borderline corresponding to the early stage of developing dyschromatopsia type III. The quantitative analysis of the test findings indicated a significantly higher value of the Color Confusion Index (CCI) in the right eye in the exposed group compared to the control group (p = 0.01), with no significant difference in the CCI in the left eye. In the exposed group, the CCI in the right eye was significantly higher than the CCI in the left eye (p = 0.0005). There was neither correlation between CCI and the level of urinary mercury, nor between CCI and duration of exposure. CONCLUSIONS: The results showed that the Lanthony D-15d test is useful in the detection of early toxic effects in the eyesight of the workers exposed to mercury vapor. The observed color vision impairments are borderline corresponding to the early stage of developing dyschromatopsia type III.

Comparing the effects of light alcohol consumption on human response to auditory and visual stimuli.

The purpose of this study is to examine the effects of various levels of alcohol consumption on human response to auditory and visual stimuli in terms of reaction time, movement time, total reaction time, and error rate. Placebo level and three low-level alcohol doses were randomly assigned to 20 male university student volunteers. 30 min. after consuming the alcohol or placebo, participants responded to either auditory or visual stimuli. Total reaction time increased significantly at the mid-low dose of alcohol (0.3 g/kg). For alcohol doses less than .5 g/kg, the change in total reaction time was confined to reaction time, i.e., the processing time between onset of stimulus and onset of movement. Effects of alcohol were significantly more pronounced in the choice-type tests. Notably, the effects of alcohol on total reaction time and error rate were significant for auditory but not visual stimuli.

Cannabis and temporal disintegration in experienced and naive subjects.

The effects of 3.3 and 6.6 milligrams of Delta(9)-tetrahydrocannabinol and of placebo on performance of three cognitive tasks were compared for naive subjects and experienced cannabis smokers. No differences in performance or reported subjective effects were found between these two groups. A significant decrement was found following dosage at both levels, replicating earlier findings of temporal disintegration during cannabis intoxication.

Nicotine does not enhance discrimination performance in a temporal bisection procedure.

Recent reports of selective disruption of stimulus control by drug administration and other disruptive operations in temporal discrimination procedures may be interpreted as a disruption of attention to the temporal sample stimuli. This experiment assessed the effects of nicotine, a compound that has been widely shown to increase measures of attention, on temporal discrimination performance. Pigeons responded under a psychophysical choice procedure in which responses to one key color were correct after presentation of four shorter sample durations and responses to another key color were correct after presentation of four longer sample durations. Performance under nicotine was characterized by using a model that differentiates the effects of nicotine on stimulus control, bias, and sensitivity of temporal discrimination. Nicotine selectively decreased the measure of stimulus control, but did not systematically affect the measures of timing. Mecamylamine (1.0 mg/kg) failed to antagonize the disruptive effects of nicotine. These results suggest that disruption of temporal discrimination performance in this preparation may not have been dependent on the specific pharmacology of nicotine and underscore the importance of quantitative separation of the effects of various manipulations on stimulus control from effects on timing.

Color vision impairments in schizophrenia and the role of antipsychotic medication type.

Schizophrenia patients (SCZ) demonstrate deficits in many domains of mental functioning, including visual perception. An issue that has been relatively unexplored, in terms of explaining variation in visual function in SCZ, however, is medication use. The present study explored potential medication effects on color vision in SCZ, a process that is strongly linked to dopaminergic function in the retina. SCZ patients who had clear-cut either typical (n = 29) or atypical (n = 29) monotherapy, without any other concurrent medication, and a group of age- and gender-matched healthy controls participated in the study. Color vision was assessed by the Cambridge Colour Test, using the Trivector and Ellipse subtests. The results demonstrated impaired color perception in patients with schizophrenia, especially in those receiving typical antipsychotics, but these deficits were subtle and not generalized to all parameters. Our findings are consistent with the known neurophysiology of the retina and visual pathways, and with the effects of dopamine blocking medications, but the results should be carefully interpreted.

Longitudinal evaluation of visual function and structure for detection of subclinical Ethambutol-induced optic neuropathy.

PURPOSE: To longitudinally evaluate the visual function and structure of patients taking ethambutol by various modalities and identify useful tests for detection of subclinical ethambutol-induced optic toxicity. METHODS: This retrospective study enrolled 84 patients with newly diagnosed tuberculosis treated with ethambutol. Best-corrected visual acuity (BCVA), color vision, contrast sensitivity, fundus and retinal nerve fiber layer (RNFL) photography, automated visual field (VF) test, and optical coherence tomography (OCT) were performed: prior to starting; every month during administration, and 1 month after stoppage. We longitudinally compared visual function and structure with the baseline and identified the occurrence of subclinical toxicity. RESULTS: BCVA, color vision, and contrast sensitivity showed no change from the baseline. Mean temporal RNFL thickness was significantly increased at 6 months (p = 0.014). Subclinical toxicity was found in 22 eyes of 14 patients (i.e., 13% of 168 eyes), in the forms of VFI decrease (VF index, 9 eyes of 6 patients), quadrant RNFL thickness increase (5 eyes of 4 patients), and VF pattern defect (12 eyes of 6 patients). 73% of the patients showed recovery to the baseline at 1 month post-stoppage. The risk factors for occurrence of subclinical toxicity were age, cumulative dose, and medication duration. CONCLUSION: Mean temporal RNFL thickness increased after administration. The VFI, quadrant RNFL thickness, and VF pattern defect could prove useful in assessment of subclinical toxicity. Medication duration was shown to be a strong risk factor for occurrence of subclinical toxicity.

Noradrenergic neuromodulation of human attention for emotional and neutral stimuli.

INTRODUCTION: Norepinephrine (NE) has a regulatory role in human attention. OBJECTIVE: To examine its role in emotional modulation of attention, we used an attentional blink (AB) paradigm, in the context of psychopharmacological manipulation, where targets were either emotional or neutral items. RESULTS AND DISCUSSION: We report behavioural evidence that beta-adrenergic blockade with propranolol impairs attention independent of target valence. Furthermore, this effect is centrally mediated as administration of the peripheral beta-adrenergic antagonist nadolol did not impair attention. By contrast, increasing NE tone, using the selective NE reuptake inhibitor reboxetine, improves detection of emotional stimuli. CONCLUSION: In line with theoretical and animal models, these findings provide human behavioural evidence that the adrenergic system has a modulatory influence on selective attention that in some instances depends on item valence.