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Alcohol is a rich drug affecting both the γ-amino butyric acid (GABA) and glutamatergic neurotransmitter systems. Recent findings from both modeling and pharmacological manipulation have indicated a link between GABAergic activity and oscillations measured in the gamma frequency range (30-80 Hz), but there are no previous reports of alcohol's modulation of gamma-band activity measured by magnetoencephalography (MEG) or electroencephalography (EEG). In this single-blind, placebo-controlled crossover study, 16 participants completed two study days, on one day of which they consumed a dose of 0.8 g/kg alcohol, and on the other day a placebo. MEG recordings of brain activity were taken before and after beverage consumption, using visual grating and finger abduction paradigms known to induce gamma-band activity in the visual and motor cortices respectively. Time-frequency analyses of beamformer source reconstructions in the visual cortex showed that alcohol increased peak gamma amplitude and decreased peak frequency. For the motor task, alcohol increased gamma amplitude in the motor cortex. These data support the notion that gamma oscillations are dependent, in part, on the balance between excitation and inhibition. Disruption of this balance by alcohol, by increasing GABAergic inhibition at GABAA receptors and decreasing glutamatergic excitation at N-methyl-D-aspartic acid receptors, alters both the amplitude and frequency of gamma oscillations. The findings provide further insight into the neuropharmacological action of alcohol.

Rationale GR3027 is a novel small molecule GABA-A receptor-modulating steroid antagonist, which in non-clinical studies has shown promise for treatment of human disorders due to allosteric over-activation of GABA-A receptors by neurosteroids, such as allopregnanolone. We here studied its safety, pharmacokinetics, and ability to inhibit allopregnanolone effects in humans. Methods Safety and pharmacokinetics were studied in healthy adult males receiving ascending single or multiple oral GR3027 vs. placebo. GR3027-mediated reversal of allopregnanolone effect on maximal saccadic eye velocity (SEV), and self-rated somnolence was studied in a double-blind, placebo-controlled, three-part cross-over study in which 3 or 30 mg oral GR3027 preceded 0.05 mg/kg of i.v. allopregnanolone. Results GR3027 was well tolerated, adverse events were generally mild and transient, and no dose-limiting toxicity or grade 3 adverse events were observed up to the highest single (200 mg) or multiple (100 mg every 12 h for 5 days) doses. The maximum concentration ( C max ) and systemic exposure (area under the plasma concentration-time curve from dose extrapolated to infinity [AUC 0–∞ ] and/or AUC during the dosing interval [AUC τ ]) varied linearly with dose; with dose-dependent accumulation ratios of 1.3–1.6. Allopregnanolone decreased SEV and induced somnolence in most, but not all subjects. By predefined analyses, 30 mg GR3027 significantly inhibited allopregnanolone-induced decrease in SEV ( p  = 0.03); 3 and 30 mg GR3027 non-significantly inhibited allopregnanolone-induced sedation. By post hoc analyses restricted to subjects with allopregnanolone-induced changes and the time period over which they occurred, GR3027 dose dependently inhibited allopregnanolone-induced decrease in SEV ( p  = 0.04 at 30 mg, non-significant at 3 mg) and allopregnanolone-induced sedation ( p  = 0.01/0.05 at 3/30 mg doses). Conclusion Oral GR3027 mitigates inhibition of brain function induced by allopregnanolone at doses which are clinically well tolerated and associated with linear pharmacokinetics.

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.

To explore the feasibility of using Saccadic Vector Optokinetic Perimetry (SVOP) to differentiate glaucomatous and healthy eyes. A prospective case–control study was performed using a convenience sample recruited from a single university glaucoma clinic and a group of healthy controls. SVOP and standard automated perimetry (SAP) was performed with testing order randomised. The reference standard was a diagnosis of glaucoma based a comprehensive ophthalmic examination and abnormality on standard automated perimetry (SAP). The index test was SVOP. 31 patients with glaucoma and 24 healthy subjects were included. Mean SAP mean deviation (MD) in those with glaucoma was − 8.7 ± 7.4 dB, with mean SAP and SVOP sensitivities of 23.3 ± 0.9 dB and 22.1 ± 4.3 dB respectively. Participants with glaucoma were significantly older. On average, SAP sensitivity was 1.2 ± 1.4 dB higher than SVOP (95% limits of agreement = − 1.6 to 4.0 dB). SVOP sensitivity had good ability to differentiate healthy and glaucomatous eyes with a 95% CI for area under the curve (AUC) of 0.84 to 0.96, similar to the performance of SAP sensitivity (95% CI 0.86 to 0.97, P = 0.60). For 80% specificity, SVOP had a 95% CI sensitivity of 75.7% to 94.8% compared to 77.8% to 96.0% for SAP. SVOP took considerably longer to perform (514 ± 54 s compared to 267 ± 76 s for SAP). Eye tracking perimetry may be useful for detection of glaucoma but further studies are needed to evaluate SVOP within its intended sphere of use, using an appropriate design and independent reference standard.

How movements are continuously adapted to physiological and environmental changes is a fundamental question in systems neuroscience. While many studies have elucidated the mechanisms which underlie short-term sensorimotor adaptation (∼10–30 min), how these motor memories are maintained over longer-term (>3–5 days) -and thanks to which neural systems-is virtually unknown. Here, we examine in healthy human participants whether the temporo-parietal junction (TPJ) is causally involved in the induction and/or the retention of saccadic eye movements' adaptation. Single-pulse transcranial magnetic stimulation (spTMS) was applied while subjects performed a ∼15min size-decrease adaptation task of leftward reactive saccades. A TMS pulse was delivered over the TPJ in the right hemisphere (rTPJ) in each trial either 30, 60, 90 or 120 msec (in 4 separate adaptation sessions) after the saccade onset. In two control groups of subjects, the same adaptation procedure was achieved either alone (No-TMS) or combined with spTMS applied over the vertex (SHAM-TMS). While the timing of spTMS over the rTPJ did not significantly affect the speed and immediate after-effect of adaptation, we found that the amount of adaptation retention measured 10 days later was markedly larger (42%) than in both the No-TMS (21%) and the SHAM-TMS (11%) control groups. These results demonstrate for the first time that the cerebral cortex is causally involved in maintaining long-term oculomotor memories. •Adaptation of ocular saccades involves the temporo-parietal junction.•Acquisition phase was unaffected by transcranial magnetic stimulation of this area.•However retention of adaptation 10 days after acquisition was strongly enhanced.

Our ability to process visual information is fundamentally limited. This leads to competition between sensory information that is relevant for top-down goals and sensory information that is perceptually salient, but task-irrelevant. The aim of the present study was to identify, from EEG recordings, pre-stimulus and pre-saccadic neural activity that could predict whether top-down or bottom-up processes would win the competition for attention on a trial-by-trial basis. We employed a visual search paradigm in which a lateralized low contrast target appeared alone, or with a low (i.e., non-salient) or high contrast (i.e., salient) distractor. Trials with a salient distractor were of primary interest due to the strong competition between top-down knowledge and bottom-up attentional capture. Our results demonstrated that 1) in the 1-sec pre-stimulus interval, frontal alpha (8-12 Hz) activity was higher on trials where the salient distractor captured attention and the first saccade (bottom-up win); and 2) there was a transient pre-saccadic increase in posterior-parietal alpha (7-8 Hz) activity on trials where the first saccade went to the target (top-down win). We propose that the high frontal alpha reflects a disengagement of attentional control whereas the transient posterior alpha time-locked to the saccade indicates sensory inhibition of the salient distractor and suppression of bottom-up oculomotor capture.

Eye movement circuitry involved in saccade production offers a model for studying cognitive control: visually guided prosaccades are stimulus-directed responses, while goal-driven antisaccades rely upon more complex control processes to inhibit the prepotent tendency to look toward a cue, transform its spatial location, and generate a volitional saccade in the opposite direction. By manipulating the relative probability of these saccade types, we measured participants’ behavioral responses to different levels of implicit trial-type probability and task-switching demands in conditions with relatively long inter-trial fixation and trial-type cue lengths. Results indicated that when prosaccades were less probable in a run, more prosaccade errors were generated; however, for antisaccades, trial-type probability had no effect on the percent of correct responses. For reaction times, specifically in runs with a larger probability of antisaccade trials, latencies increased for both anti- and pro-saccades. Furthermore, task switching resulted in a lower percentage of correct responses on switched trials, but a prior antisaccade trial led to slower reaction times for both trial types (i.e., a task switch cost for prosaccades and switch benefit for antisaccades). These findings indicate that cognitive control demands and residual inhibition from antisaccades alter performance relative to trial-type probability and task switching within a run, with the prosaccade task showing greater susceptibility to the influence of a large probability of cognitively complex antisaccades.

People with autism spectrum disorder (ASD) show reduced interest towards social aspects of the environment and a lesser tendency to follow other people's gaze in the real world. However, most studies have shown that people with ASD do respond to eye-gaze cues in experimental paradigms, though it is possible that this behaviour is based on an atypical strategy. We tested this possibility in adults with ASD using a cueing task combined with eye-movement recording. Both eye gaze and arrow pointing distractors resulted in overt cueing effects, both in terms of increased saccadic reaction times, and in proportions of saccades executed to the cued direction instead of to the target, for both participant groups. Our results confirm previous reports that eye gaze cues as well as arrow cues result in automatic orienting of overt attention. Moreover, since there were no group differences between arrow and eye gaze cues, we conclude that overt attentional orienting in ASD, at least in response to centrally presented schematic directional distractors, is typical.

Saccadic eye movements are driven by motor commands that are continuously modified so that errors created by eye muscle fatigue, injury, or—in humans—wearing spectacles can be corrected. It is possible to rapidly adapt saccades in the laboratory by introducing a discrepancy between the intended and actual saccadic target. Neurophysiological and lesion studies in the non-human primate as well as neuroimaging and patient studies in humans have demonstrated that the oculomotor vermis (lobules VI and VII of the posterior cerebellum) is critical for saccadic adaptation. We studied the effect of transiently disrupting the function of posterior cerebellum with repetitive transcranial magnetic stimulation (rTMS) on the ability of healthy human subjects to adapt saccadic eye movements. rTMS significantly impaired the adaptation of the amplitude of saccades, without modulating saccadic amplitude or variability in baseline conditions. Moreover, increasing the intensity of rTMS produced a larger impairment in the ability to adapt saccadic size. These results provide direct evidence for the role of the posterior cerebellum in man and further evidence that TMS can modulate cerebellar function.

Search asymmetry is characterized by the detection of a feature-present target amidst feature-absent distractors being efficient and unaffected by the number of distractors, whereas detection of a feature-absent target amidst feature-present distractors is typically inefficient and affected by the number of distractors. Although studies have attempted to investigate this phenomenon with infants (e.g., Adler, Inslicht, Rovee-Collier, & Gerhardstein in Infant Behavioral Development, 21, 253–272, 1998 ; Colombo, Mitchell, Coldren, & Atwater in Journal of Experimental Psychology: Learning, Memory and Cognition, 19 , 98–109, 1990 ), due to methodological limitations, their findings have been unable to definitively establish the development of visual search mechanisms in infants. The present study assessed eye movements as a means to examine an asymmetry in responding to feature-present versus feature-absent targets in 3-month-olds, relative to adults. Saccade latencies to localize a target (or a distractor, as in the homogeneous conditions) were measured as infants and adults randomly viewed feature-present (R among Ps), feature-absent (P among Rs), and homogeneous (either all Rs or all Ps) arrays at set sizes of 1, 3, 5, and 8. Results indicated that neither infants’ nor adults’ saccade latencies to localize the target in the feature-present arrays were affected by increasing set sizes, suggesting that localization of the target was efficient. In contrast, saccade latencies to localize the target in the feature-absent arrays increased with increasing set sizes for both infants and adults, suggesting an inefficient localization. These findings indicate that infants exhibit an asymmetry consistent with that found with adults, providing support for functional bottom-up selective attention mechanisms in early infancy.