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Concussion can lead to various symptoms such as balance problems, memory impairments, dizziness, and/or headaches. It has been previously suggested that during self-motion relevant tasks, individuals with concussion may rely heavily on visual information to compensate for potentially less reliable vestibular inputs and/or problems with multisensory integration. As such, concussed individuals may also be more sensitive to other visually-driven sensations such as visually induced motion sickness (VIMS). To investigate whether concussed individuals are at elevated risk of experiencing VIMS, we exposed participants with concussion (n = 16) and healthy controls (n = 15) to a virtual scene depicting visual self-motion down a grocery store aisle at different speeds. Participants with concussion were further separated into symptomatic and asymptomatic groups. VIMS was measured with the SSQ before and after stimulus exposure, and visual dependence, self-reported dizziness, and somatization were recorded at baseline. Results showed that concussed participants who were symptomatic demonstrated significantly higher SSQ scores after stimulus presentation compared to healthy controls and those who were asymptomatic. Visual dependence was positively correlated with the level of VIMS in healthy controls and participants with concussion. Our results suggest that the presence of concussion symptoms at time of testing significantly increased the risk and severity of VIMS. This finding is of relevance with regards to the use of visual display devices such as Virtual Reality applications in the assessment and rehabilitation of individuals with concussion., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Self-induced seizures were first described in 1827. A majority of authors found that in unselected patients with epilepsy, the prevalence rate of these seizures was 1%. In patients with photosensitive epilepsy, there was roughly a 25% prevalence. Apart from visual stimulation, many other mechanisms of self-induction have been described. A feeling of pleasure or relaxation during seizures may be a reason for self-inductive behaviour. But often the procedure of self-induction is experienced as involuntary. Treatment is always difficult. Behavioral therapy has been proven effective in some patients. In patients with photosensitive epilepsy, sunglasses are recommended. Fenfluramine, clonazepam and valproate seem to be a bit more effective than other drugs. After all, the treatment effect depends on the motivation of the patient to change the condition., Competing Interests: J Rösche hat Vortragshonorare von Eisai erhalten. MIR Dudek und O Kohnen haben keine Interessenskonflikte., (Thieme. All rights reserved.)

Esophagogastroduodenoscopy (EGD) has become an indispensable examination to discover upper gastrointestinal diseases, including cancer, and perform endoscopic treatment. However, many individuals who undergo the procedure have feelings of anxiety and fear regarding EGD. Although the use of medication for sedation during EGD is useful for reducing anxiety and the stability of hemodynamics, sedation may increase the likelihood of complications. Several noninvasive distractions have been introduced to decrease pain and anxiety during endoscopic examinations;however, most assessments of these distractions evaluated subjective items such as impression. We herein add the results of our studies using objective items and review the effectiveness of distractions for EGD. J. Med. Invest. 69 : 8-18, February, 2022.

Bergmann glia (BG) are highly specialized radial astrocytes of the cerebellar cortex, which play a key role in the uptake of synaptic glutamate via the excitatory amino acid transporter EAAT1. Multiple lines of evidence suggest that in cerebellar neurodegenerative diseases reactive BG has a negative impact on neuronal function and survival through compromised EAAT activity. A family of such diseases are those caused by expansion of CAG repeats in genes of the ataxin family, resulting in spinocerebellar ataxias (SCA). We investigated the contribution of BG to the pathogenesis of cerebellar neurodegeneration in a model of SCA1, which was induced by expression of a polyglutamine mutant of ataxin-1 (ATXN1[Q85]) in BG specifically. We compared the outcomes with a novel model where we triggered excitotoxicity by a chronic optogenetic activation of BG with channelrhodopsin-2 (ChR2). In both cases we detected evidence of reduced glutamate uptake manifested by prolongation of excitatory postsynaptic currents in Purkinje cells which is consistent with documented reduction of expression and/or function of EAAT1. In both models we detected astroglyosis and Purkinje cells atrophy. Finally, the same pattern was detected in a knock-in mouse which expresses a polyglutamine mutant ataxin-1 ATXN1[Q154] in a non-cell-selective manner. Our results suggest that ATXN1[Q85] and ChR2-induced insult targeted to BG closely mimics SCA1 pathology, where excessive glutamate signaling appears to be a common feature likely being an important contributor to cerebellar neurodegeneration., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Flicker light stimulation can induce short-term alterations in consciousness including hallucinatory color perception and geometric patterns. In the study at hand, the subjective experiences during 3 Hz and 10 Hz stroboscopic light stimulation of the closed eyes were assessed. In a within-subjects design (N = 24), we applied the Positive and Negative Affect Schedule (mood state), time perception ratings, the Altered State of Consciousness Rating Scale, and the Phenomenology of Consciousness Inventory. Furthermore, we tested for effects of personality traits (NEO Five-Factor Inventory-2 and Tellegen Absorption Scale) on subjective experiences. Such systematic quantification improves replicability, facilitates comparisons between pharmacological and non-pharmacological techniques to induce altered states of consciousness, and is the prerequisite to study their underlying neuronal mechanisms. The resulting data showed that flicker light stimulation-induced states were characterized by vivid visual hallucinations of simple types, with effects strongest in the 10 Hz condition. Additionally, participants' personality trait of Absorption scores highly correlated with the experienced alterations in consciousness. Our data demonstrate that flicker light stimulation is capable of inducing visual effects with an intensity rated to be similar in strength to effects induced by psychedelic substances and thereby support the investigation of potentially shared underlying neuronal mechanisms., Competing Interests: The authors have declared that no competing interests exist.

Huntington's disease (HD) is a neurodegenerative disease caused by a CAG triplet repeat expansion in the Huntingtin gene. Metabolic and microvascular abnormalities in the brain may contribute to early physiological changes that subserve the functional impairments in HD. This study is intended to investigate potential abnormality in dynamic changes in cerebral blood volume (CBV) and cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO 2 ) in the brain in response to functional stimulation in premanifest and early manifest HD patients. A recently developed 3-D-TRiple-acquisition-after-Inversion-Preparation magnetic resonance imaging (MRI) approach was used to measure dynamic responses in CBV, CBF, and CMRO 2 during visual stimulation in one single MRI scan. Experiments were conducted in 23 HD patients and 16 healthy controls. Decreased occipital cortex CMRO 2 responses were observed in premanifest and early manifest HD patients compared to controls ( P  < 0.001), correlating with the CAG-Age Product scores in these patients ( R 2  = 0.4, P  = 0.001). The results suggest the potential value of this reduced CMRO 2 response during visual stimulation as a biomarker for HD and may illuminate the role of metabolic alterations in the pathophysiology of HD.

The positron emission tomography radioligand [ 11 C]UCB-J binds to synaptic vesicle glycoprotein 2 A (SV2A), a regulator of vesicle release. Increased neuronal firing could potentially affect tracer concentrations if binding site availability is altered during vesicle exocytosis. This study assessed whether physiological brain activation induces changes in [ 11 C]UCB-J tissue influx ( K 1 ), volume of distribution ( V T ), or binding potential ( BP ND ). Healthy volunteers ( n  = 7) underwent 60-min [ 11 C]UCB-J PET scans at baseline and during intermittent presentation of 8-Hz checkerboard visual stimulation. Sensitivity to intermittent changes in kinetic parameters was assessed in simulations, and visual stimulation was repeated using functional magnetic resonance imaging to characterize neural responses. V T  and K 1 were determined using the one-tissue compartment model and BP ND using the simplified reference tissue model. In primary visual cortex, K 1 increased 34.3 ± 15.5% ( p  = 0.001) during stimulation, with no change in other regions ( p s   >   0.12). K 1 change was correlated with fMRI BOLD response (r = 0.77, p  = 0.043). There was no change in V T (-3.9 ± 8.8%, p  =   0.33) or BP ND (-0.2 ± 9.6%, p  =   0.94) in visual cortex nor other regions ( p s   >   0.19). Therefore, despite robust increases in regional tracer influx due to blood flow increases, binding measures were unchanged during stimulation. [ 11 C]UCB-J V T and BP ND are likely to be stable in vivo measures of synaptic density.

Repetitive mild traumatic brain injury (mTBI) has been called the "signature injury" of military service members in the Iraq and Afghanistan wars and is highly comorbid with post-traumatic stress disorder (PTSD). Correct attribution of adverse blast-induced mTBI and/or PTSD remains challenging. Pre-clinical research using animal models can provide important insight into the mechanisms by which blast produces injury and dysfunction-but only to the degree by which such models reflect the human experience. Avoidance of trauma reminders is a hallmark of PTSD. Here, we sought to understand whether a mouse model of blast reproduces this phenomenon, in addition to blast-induced physical injuries. Drawing on well-established work from the chronic stress and Pavlovian conditioning literature, we hypothesized that even while one is anesthetized during blast exposure, environmental cues encountered in the peri-blast environment could be conditioned to evoke aversion/dysphoria and re-experiencing of traumatic stress. Using a pneumatic shock tube that recapitulates battlefield-relevant open-field blast forces, we provide direct evidence that stress is inherent to repetitive blast exposure, resulting in chronic aversive/dysphoric-like responses to previous blast-paired cues. The results in this report demonstrate that, although both single and repetitive blast exposures produce acute stress responses (weight loss, corticosterone increase), only repetitive blast exposure also results in co-occurring aversive/dysphoric-like stress responses. These results extend appreciation of the highly complex nature of repetitive blast exposure; and lend further support for the potential translational relevance of animal modeling approaches currently used by multiple laboratories aimed at elucidating the mechanisms (both molecular and behavioral) of repetitive blast exposure.

Humor has been considered an effective emotion regulation strategy, and some behavioral studies have examined its superior effects on negative emotion regulation. However, its neural mechanisms remain unknown. Our functional magnetic resonance imaging study directly compared the emotion regulation effects and neural bases of humorous coping (reappraisal) and ordinary reappraisal following exposure to negative pictures. The behavioral results suggested that humorous reappraisal was more effective in downregulating negative emotions and upregulating positive emotions both in the short and long term. We also found 2 cooperative neural pathways involved in coping with negative stimuli by means of humor: the "hippocampal-thalamic-frontal pathway" and the "amygdala-cerebellar pathway." The former is associated with the restructuring of mental representations of negative situations and accompanied by an insightful ("Aha!") experience, while the latter is associated with humorous emotional release and accompanied by an expression of laughter ("Haha!"). Furthermore, the degree of hippocampal functional connectivity with both the thalamus and frontal cortex was positively correlated with changes in positive emotion, and this result implied that the degree of emotion regulation could be strongly directly related to the depth of cognitive reconstruction. These findings highlight that regulating negative emotions with humor involves cognitive restructuring and the release of positive emotions., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Sunflower syndrome is a rare photosensitive epilepsy which has received little attention in recent medical literature. The historical cases documenting the epilepsy's stereotyped handwaving motion in front of light characterized the behavior as self-inducing seizures via mimic of stroboscopic effect. However, the relationship between handwaving episodes and attendant generalized electroencephalogram abnormalities, and an appreciation of the compulsive attraction the sun and other light sources hold for these patients, suggest the handwaving motion may be a part of the seizure rather than a mechanism of self-induction. The lack of awareness of Sunflower syndrome often leads to misdiagnosis. The seizures are often refractory to traditional anticonvulsant medication, and patients resort to behavioral intervention, such as hats and sunglasses, to reduce handwaving episodes. Further study is required to determine the syndrome's natural history and to identify more effective treatment options. WHAT THIS PAPER ADDS: Sunflower syndrome is a rare condition that is often misdiagnosed. Awareness of the clinical and electroencephalogram characteristics of Sunflower syndromemay reduce the prevalence of misdiagnosis., (© 2020 Mac Keith Press.)

Video-EEG monitoring is an established gold-standard procedure for diagnosis and differentiation of epileptic and non-epileptic seizures. Epilepsy misdiagnosis, to which factors such as EEG artifact misinterpretation contribute to, is common, and can have long-lasting iatrogenic repercussions to the clinical management of affected patients. Among the many types of responses to photic stimulation, artifacts and physiologic and epileptic responses are possible. All of these can interfere with EEG interpretation when provoked by a source of illumination. Photic-induced responses are of increasing relevance given the ubiquity of screens and other light-emitting electronics in our modern world. One of these, the photoparoxysmal response, is a frequent finding in photosensitive patients with genetic generalized epilepsies. Various responses beyond abnormal occurrence of cortical spikes or spike-and-wave discharges are known to occur on EEG in response to intermittent photic stimulation (IPS), with different clinical implications. To our knowledge, we report a unique electronegative photoparoxysmal response during video-EEG monitoring induced by fluctuating illumination caused by a distant television screen. This response mimicked an extratemporal seizure in a young woman with frontal lobe epilepsy, admitted for presurgical evaluation. Novel electronegative responses to electronic devices during video-EEG monitoring merit consideration by EEG interpreters to help avoid misdiagnosis.

No reliable quantitative and objective measurement method for virtual reality (VR) sickness has been firmly established to date. Electroencephalography (EEG) may be a strong candidate to evaluate VR sickness objectively. However, no test-retest evaluation has been made for VR sickness using EEG. To recruit VR sickness-sensitive participants, we tested 858 participants (age = 20's-50's) using the Motion Sickness Susceptibility Questionnaire (MSSQ). Among them, we recruited 21 males (average age = 25.0) who obtained the 75th percentile of scores on the MSSQ (32.9 ± 5.7). VR sickness was evaluated twice (one week apart) using EEG with VR video content designed to cause VR sickness. A Simulation Sickness Questionnaire (SSQ) was also used to evaluate VR sickness. In terms of the reliability of EEG, ICC and Cronbach's alpha analyses showed that three waves (delta, theta, and alpha) were consistent in two areas (frontal and central). A significant difference in EEG was also found repeatedly between the baseline and VR sickness (delta, theta, and alpha) in two areas (frontal and central). We evaluated EEG for its reliability and found specific waves and areas that showed good consistency and significant changes associated with VR sickness. These findings may support further research of VR sickness evaluation., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

A 15-year-old girl was admitted to the emergency room because of a bilateral tonic-clonic seizure. The family reported that the episode began with rapid hand movements in front of the patient's eyes while staring at the sun. The patient has a history of multiple admissions in the emergency department due to similar events since the age of eight. Most occurrences were associated with episodes of frustration. The review of the literature has shown that this type of phenomenon, designated in some studies by sunflower syndrome, may be overlooked in patients with photosensitive epilepsy. Despite the unknown etiology, there are several reasons why patients experience this type of behavior, and thus a multidisciplinary approach is needed.

Degeneration of photoreceptors caused by excessive illumination, inherited mutations, or aging is the principal pathology of blinding diseases. Pharmacological compounds that stabilize the visual receptor rhodopsin and modulate the cellular pathways triggering death of photoreceptors could avert this pathology. Interestingly, flavonoids can modulate the cellular processes, such as oxidative stress, inflammatory responses, and apoptosis, that are activated during retinal degeneration. As we found previously, flavonoids also bind directly to unliganded rod opsin, enhancing its folding, stability, and regeneration. In addition, flavonoids stimulate rhodopsin gene expression. Thus, we evaluated the effect of two main dietary flavonoids, quercetin and myricetin, in ATP-binding cassette subfamily A member 4 -/- /retinol dehydrogenase 8 -/- and wild-type BALB/c mice susceptible to light-induced photoreceptor degeneration. Using in vivo imaging, such as optical coherence tomography, scanning laser ophthalmoscopy, and histologic assessment of retinal morphology, we found that treatment with these flavonoids prior to light insult remarkably protected retina from deterioration and preserved its function. Using high-performance liquid chromatography-mass spectrometry analysis, we detected these flavonoids in the eye upon their intraperitoneal administration. The molecular events associated with the protective effect of quercetin and myricetin were related to the elevated expression of photoreceptor-specific proteins, rhodopsin and cone opsins, decreased expression of the specific inflammatory markers, and the shift of the equilibrium between cell death regulators BCL2-associated X protein (BAX) and B-cell lymphoma 2 toward an antiapoptotic profile. These results were confirmed in photoreceptor-derived 661W cells treated with either H 2 O 2 or all- trans -retinal stressors implicated in the mechanism of retinal degeneration. Altogether, flavonoids could have significant prophylactic value for retinal degenerative diseases. SIGNIFICANCE STATEMENT: Flavonoids commonly present in food exhibit advantageous effects in blinding diseases. They bind to and stabilize unliganded rod opsin, which in excess accelerates degenerative processes in the retina. Additionally, flavonoids enhance the expression of the visual receptors, rod and cone opsins; inhibit the inflammatory reactions; and induce the expression of antiapoptotic markers in the retina, preventing the degeneration in vivo. Thus, flavonoids could have a prophylactic value for retinal degenerative diseases., Competing Interests: Conflicts of Interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2020 by The American Society for Pharmacology and Experimental Therapeutics.)

Aim: In clinical practice, there is a prevailing notion that photosensitivity mostly occurs in children with epilepsy (CWE) with idiopathic generalized epilepsy. We investigated the distribution of epilepsy types and etiology in photosensitive children and the associations with specific clinical and electroencephalogram (EEG) variables., Methods: In this retrospective cohort study, clinical data were acquired from all children that showed photosensitivity during systematic intermittent photic stimulation (IPS), over a 10-year interval at a tertiary level Children's Hospital, Winnipeg. Patient demographics, EEG findings, and clinical data and symptoms during IPS were abstracted. Classification of diagnoses using the International League Against Epilepsy (ILAE) 2017 guidelines was done by an expert panel., Results: Seventy-eight photosensitive children were identified. Forty (51.3%) had generalized epilepsy (idiopathic: 27, structural: 2, other: 11) compared with 19 (24.4%) focal (idiopathic: 1, structural: 2, other: 16), 8 (10.3%) combined focal and generalized (structural: 4, other: 4), and 11 (14.1%) unknown epilepsy (other: 11); (χ 2 (3) = 32.1, p = .000). Self-sustaining or outlasting photoparoxysmal responses (PPRs) occurred in association with all epilepsy types; however, the EEGs of focal CWE without treatment comprised almost solely of PPRs which outlasted the stimulus (8/10), in contrast to only 8/17 of focal CWE with treatment and to 13/26 of generalized epilepsy without treatment. Most frequency intervals in individual patients were less under treatment: a decrease in standardized photosensitivity range (SPR) was seen in 5 CWE, an increase in 2, and no change in 1 during treatment. Both CWE with focal and generalized epilepsy showed abnormal activity on EEG during hyperventilation (40% vs 65.7%). Thirteen out of 14 CWE with clinical signs during IPS had independent spontaneous epileptiform discharges (SEDs) in the EEG recording., Conclusion: Photosensitivity occurs in all types of epilepsy rather than in idiopathic generalized epilepsy alone. Surprisingly, there is a tendency for focal epilepsy to be associated with self-sustaining PPRs, especially when no treatment is used. Treatment tends to make the PPR more self-limiting and decrease the SPR. There is a tendency that clinical signs during IPS occur in EEGs in individuals with SEDs., Competing Interests: Declaration of competing interest The authors have no conflict of interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The angiotensin-II antagonist losartan is a promising candidate that has enhanced extinction in a post-traumatic stress disorder (PTSD) animal model and was related to reducing PTSD symptom development in humans. Here, we investigate the neurocognitive mechanisms underlying these results, testing the effect of losartan on data-driven and contextual processing of traumatic material, mechanisms proposed to be relevant for PTSD development. In a double-blind between-subject design, 40 healthy participants were randomised to a single oral dose of losartan (50 mg) or placebo, 1 h before being exposed to distressing films as a trauma analogue while heart rate (HR) was measured. Peritraumatic processing was investigated using blurry picture stimuli from the films, which transformed into clear images. Data-driven processing was measured by the level of blurriness at which contents were recognised. Contextual processing was measured as the amount of context information retrieved when describing the pictures' contents. Negative-matched control images were used to test perceptual processing of peripheral trauma-cues. Post-traumatic stress symptoms were assessed via self-report questionnaires after analogue trauma and an intrusion diary completed over 4 days following the experiment. Compared to placebo, losartan facilitated contextual processing and enhanced detail perception in the negative-match pictures. During the films, the losartan group recorded lower HR and higher HR variability, reflecting lower autonomic stress responses. We discuss potential mechanisms of losartan in preventing PTSD symptomatology, including the role of reduced arousal and increased contextual processing during trauma exposure, as well as increased threat-safety differentiation when encountering peripheral trauma-cues in the aftermaths of traumatic events.

Rationale: Exposure to chronic constant light (CCL) has a detrimental impact on circadian rhythms of motor activity and sleep/wake cycles. Agomelatine is an atypical antidepressant showing a chronotropic activity., Objectives: In this study, we explored the role of melatonin (MT) receptors and brain-derived neurotrophic factor (BDNF) in the brain in the mechanism underlying the effects of agomelatine on diurnal variations of motor activity, sleep/wake cycle, and sleep architecture in a rat model of CCL., Methods: In Experiment #1, home cage activity was monitored automatically with cameras for a period of 24 h. The diurnal rhythm of MT 1, MT 2 receptors, and BDNF expression in the hippocampus and frontal cortex (FC), was tested using the ELISA test. In Experiment #2, rats were equipped with electroencephalographic (EEG) and electromyographic (EMG) electrodes and recordings were made under basal conditions (12:12 LD cycle + vehicle), LL + vehicle and LL + agomelatine (40 mg/kg/day for 21 days)., Results: The rats exposed to CCL showed an impaired diurnal rhythm of motor activity and sleep/wake cycle with reduced NREM sleep and delta power and increased REM sleep and theta power. The duration and number of episodes of the wake were diminished during the subjective dark phase in this group. The circadian rhythm of MT 1 and MT 2 receptors and their expression did not change in the hippocampus and FC under CCL exposure, while the BDNF levels in the hippocampus decreased during the subjective light phase. Agomelatine restored the diurnal rhythm of motor activity, disturbed sleep/wake cycle, and sleep architecture, which effect was accompanied by an increase in MT 1 receptor and BDNF expression in the hippocampus at 10:00 in CCL rats., Conclusions: These findings support the value of agomelatine as an antidepressant that can adjust circadian homeostasis of motor activity and sleep/wake cycle in a CCL model.

Major depressive disorder (MDD) has been associated with changes in the biological stress systems, including the locus coeruleus-noradrenergic system. Accumulated evidence suggests an upregulation of central alpha2-receptors, leading to decreased noradrenergic activity on a central level in MDD patients. Adverse childhood experiences (ACE) such as physical or sexual abuse might contribute to those changes. Furthermore, noradrenaline can affect cognitive processes, e.g. learning and memory. Cognitive dysfunctions constitute an important symptom of MDD. We aimed to investigate the relationship of alpha2-receptor dysregulation with learning processes in MDD by conducting a differential fear conditioning paradigm after double-blind administration of the alpha2-receptor antagonist yohimbine versus placebo. To investigate the role of ACE systematically, we included four groups of healthy participants and MDD patients with and without ACE (MDD-/ACE-: N = 44, MDD-/ACE+: N = 26, MDD+/ACE-: N = 24, MDD+/ACE+: N = 24; without antidepressant medication). We found increased noradrenergic activity after yohimbine administration across groups as measured by alpha-amylase and blood pressure. Overall, fear responses were higher after yohimbine as indicated by skin conductance responses and fear-potentiated startle responses. While we found no significant MDD effect, ACE had significant impact on the ability to discriminate between both conditioned stimuli (CS+ predicting an aversive stimulus, CS- predicting none), depending on drug condition. After yohimbine, CS discrimination decreased in individuals without ACE, but not in individuals with ACE. Differences in the response to yohimbine might be explained by aberrant alpha2-receptor regulation in individuals with ACE. Impaired discrimination of threat and safety signals might contribute to enhanced vulnerability following ACE., (Copyright © 2019. Published by Elsevier Inc.)

Objective: To review clinical and pre-clinical evidence supporting the role of visual pathways, from the eye to the cortex, in the development of photophobia in headache disorders., Background: Photophobia is a poorly understood light-induced phenomenon that emerges in a variety of neurological and ophthalmological conditions. Over the years, multiple mechanisms have been proposed to explain its causes; however, scarce research and lack of systematic assessment of photophobia in patients has made the search for answers quite challenging. In the field of headaches, significant progress has been made recently on how specific visual networks contribute to photophobia features such as light-induced intensification of headache, increased perception of brightness and visual discomfort, which are frequently experienced by migraineurs. Such progress improved our understanding of the phenomenon and points to abnormal processing of light by both cone/rod-mediated image-forming and melanopsin-mediated non-image-forming visual pathways, and the consequential transfer of photic signals to multiple brain regions involved in sensory, autonomic and emotional regulation., Conclusion: Photophobia phenotype is diverse, and the relative contribution of visual, trigeminal and autonomic systems may depend on the disease it emerges from. In migraine, photophobia could result from photic activation of retina-driven pathways involved in the regulation of homeostasis, making its association with headache more complex than previously thought.

Photosensitive is probably caused by multiple factors including gender, familiar, etc. We aim to study the clinical and EEG features of Chinese Han patients with photosensitivity. A total of 5482 consecutive patients with possible epilepsy from 3 center in China. Of the 73 patients with PPR to IPS, 48 were female. 69.9% patients were evoked by frequency ranged 8 Hz-25 Hz, with accompanying seizures in 13 patients. 6 of 9 patients with eyes closure sensitivity experienced epileptic seizures during IPS. We found some new features: 1) The patients with eyes closure sensitivity apt to experience electro-clinical seizures provoked by IPS; 2) Female epilepsy patients with PPR and ECS maybe difficult to be seizure free. Preventive measures for related seizures should be performed to the patients with generalized PPR, upper threshold evoking frequency, and eyes closure sensitivity when they received the IPS., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Video slot machines are associated with both accelerated transition into problematic forms of gambling, as well as psychosocial harm above and beyond other forms of gambling. A growing body of evidence is uncovering how key design features of multiline slot machines produce an inflated experience of reward, despite the fact that these features offer no overall financial benefit to the player. A pernicious example of this are 'losses disguised as wins' (LDWs), which occur when simultaneous bets placed on multiple lines result in a winning combination that returns an amount greater than zero, but less the total wager. These events are usually accompanied by the same celebratory sounds and animations that accompany true wins. We argue that LDWs may leverage neuropsychological phenomena that underlie reinforcement learning and contribute to extended or repetitive use and gambling-related harm. While other characteristics of slot machine gambling have been examined by cognitive neuroscientists, this feature has not yet received attention. Neuroscientific methods can be used to assess the impact of LDWs on the human reward system, to assess the claim that these events are a reinforcing and contributing factor in the development of harmful play. Positive findings would provide further persuasive evidence in support of strategies to minimise gambling harm through the regulation of machine design., (© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Objective: Treatment options for seizure clusters are limited; the need for easy-to-administer treatments remains. The Staccato system delivers drug deep into the lung via inhalation. In this phase 2a study, we investigated the ability of three different doses of Staccato alprazolam to suppress the electroencephalographic (EEG) photoparoxysmal response (PPR) compared with placebo in participants with photosensitive seizures., Methods: Adults (18-60 years) with a diagnosis and history of PPR on EEG with or without an epilepsy diagnosis were eligible to participate. Participants received Staccato alprazolam 0.5, 1.0, and 2.0 mg, and Staccato placebo (twice) in random order. Intermittent photic stimulation and clinical assessments were performed at one predose and seven postdose time points. The primary endpoint of the study was the change in standardized photosensitivity range (SPR) in participants receiving each dose of Staccato alprazolam., Results: Fifteen participants with a prior epilepsy diagnosis were screened; five were enrolled, randomized, and completed the study. All participants were white females with a mean (SD) age of 27.2 (6.8) years. All doses of Staccato alprazolam reduced the SPR at 2 minutes; the effect was sustained through 4 hours for the 0.5-mg dose and 6 hours for the 1.0- and 2.0-mg doses. The magnitude and duration of sedation and sleepiness were dose-related. Four participants (80%) experienced ≥1 adverse event (AE); none was severe or serious. Cough, diarrhea, dysgeusia, oral dysesthesia, sedation, and somnolence were experienced by two participants (40%) each., Significance: This proof-of-concept study demonstrated that Staccato alprazolam 0.5, 1.0, and 2.0 mg rapidly suppressed epileptiform activity in photosensitive participants with epilepsy. The AE profile of Staccato alprazolam was similar to what has been reported for alprazolam for other indications. The results support further development of Staccato alprazolam as a rescue medication for the acute treatment of seizures., (© 2019 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.)

Individual differences in neural response to appetitive and aversive stimuli may confer vulnerability to stress-related psychopathology, including depression and anxiety. However, the specificity of this association with symptoms of depression and anxiety within the context of real-world stress is not well understood. The present study examined whether neural responses to appetitive and aversive images, measured by the late positive potential (LPP), prospectively predict symptoms of depression and/or anxiety during the transition to university-a common, major life stressor-in 70 female emerging adults. A blunted LPP to appetitive stimuli at the start of the university year was uniquely associated with greater symptoms of depression six weeks later, after controlling for time one depressive symptoms and neural responses to aversive and neutral stimuli. These findings suggest that a blunted LPP to appetitive images may be biomarker of risk for developing symptoms of depression, and not anxiety, following life stress., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Past events, particularly emotional experiences, are often vividly recollected. However, it remains unclear how qualitative information, such as low-level visual salience, is reconstructed and how the precision and bias of this information relate to subjective memory vividness. Here, we tested whether remembered visual salience contributes to vivid recollection. In three experiments, participants studied emotionally negative and neutral images that varied in luminance and color saturation, and they reconstructed the visual salience of each image in a subsequent test. Results revealed, unexpectedly, that memories were recollected as less visually salient than they were encoded, demonstrating a novel memory-fading effect, whereas negative emotion increased subjective memory vividness and the precision with which visual features were encoded. Finally, memory vividness tracked both the precision and remembered salience (bias) of visual information. These findings provide evidence that low-level visual information fades in memory and contributes to the experience of vivid recollection.

Objective: This study investigated a potential association between visual factors and symptoms related to migraine. It was predicted that photophobia and visual aura would be positively associated with interictal light sensitivity and visual headache triggers (flicker, glare, and eyestrain), and that these 2 visual symptoms would also be associated., Background: Previous studies have found independent neurophysiological associations between several visual factors and symptoms related to headache disorders. Many of these connections appear to be associated with increased cortical hypersensitivity, a phenomenon that might be in part due to repeated avoidance and reduced tolerance to triggers. If true, and if associations between visual factors and symptoms can be established, this may have implications for an exposure-based treatment for migraine symptoms., Methods: Four hundred and ninety-one participants (411 female, 80 male) were recruited through Griffith University (AUS), Headache Australia, Pain Australia, and through social media. Participants were grouped based on the presence of headache disorder symptoms and the presence or absence of photophobia and/or visual aura. A cross-sectional online survey design was utilized to gather information pertaining to interictal light sensitivity, visual triggers, and visual symptoms., Results: With respect to interictal light sensitivity and photophobia, a significant difference (P < .001, eta squared [η 2 ] = 0.084) was found between the 3 groups, where headache disorder participants with photophobia (group A1; mean [M] = 2.5, standard deviation [SD] = 0.97) reported significantly greater light sensitivity than participants with headache disorder and no photophobia (A2; M = 1.68, SD = 0.62) and control group participants (A3; M = 1.82, SD = 0.85). This pattern was repeated for participants reporting flicker as a headache trigger (P < .001, η 2 = 0.061), with group A1 (M = 2.45, SD = 1.24) significantly higher than groups A2 (M = 1.68, SD = 0.83) and A3 (M = 1.68, SD = 0.89), and was also seen for glare as a headache trigger (P < .001, η 2 = 0.092), with group A1 (M = 2.92, SD = 0.96) significantly higher than A2 (M = 2.31, SD = 0.89) and A3 (M = 2.09, SD = 0.93). This pattern of results was not replicated for headache disorder participants with and without visual aura. A significant association (P < .001) was found between photophobia and visual aura in headache disorder participants based on a chi-square test of independence, with 86/136 participants reporting either both or neither visual symptom., Conclusions: This study supports a link between certain visual phenomena in headache disorder populations, and supports future research into exposure-based treatments for migraine symptoms., (© 2019 American Headache Society.)

Photosensitive epilepsy is the most common subset of reflex epilepsy in humans. It is characterized by an abnormal electroencephalogram trait known as photoparoxysmal response (PPR) corresponding to ictal symptomology in response to intermittent photic stimulation. Increased exposure to photic stimulation through technological and societal advance has had a significant impact on the incidence and interest in photosensitive epilepsy. Paralleled scientific developments have deepened our understanding of the neurophysiology underlying photosensitivity, especially in the context of deep genomic sequencing and neuroimaging. Furthermore, given the relatively predictable nature of photosensitive epilepsy, there is substantial interest in translating advancements in this field to epilepsy as a whole. Herein, we comprehensively review the epidemiology, clinical features and novel insights into the mechanism behind photosensitive epilepsy with a focus on the clinical implications of new advancements., (Published by Elsevier B.V.)

3,3'-Diindolylmethane (DIM) is a phytochemical that presents health benefits (antitumor, antioxidant, and anti-inflammatory effects). However, it is water insoluble and thermo- and photolabile, restraining its pharmaceutical applications. As a strategy to overcome such limitations, this study aimed the development and characterization of DIM-loaded nanocapsules (NCs) prepared with different compositions as well as the in vitro assessment of scavenging activity and cytotoxicity. The formulations were obtained using the interfacial deposition of preformed polymer method and were composed by Eudragit® RS100 or ethylcellulose as polymeric wall and primula or apricot oil as the core. All the formulations had adequate physicochemical characteristics: nanometric size (around 190 nm), low polydispersity index (< 0.2), pH value at acid range, high values of zeta potential, drug content, and encapsulation efficiency (~ 100%). Besides, nanoencapsulation protected DIM against UVC-induced degradation and increased the scavenging activity assessed by the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) and 1-1-diphenyl-2-picrylhydrazyl methods. The developed DIM-loaded nanocapsules were further evaluated regarding the in vitro release profile and cytotoxicity against a human glioblastoma cell line (U87 cells). The results demonstrated that the nanoencapsulation promoted a sustained release of the bioactive compound (in the range of 58-78% after 84 h) in comparison to its free form (86% after 12 h), as well as provided a superior cytotoxic effect against the U87 cells in the highest concentrations. Therefore, our results suggest that nanoencapsulation could be a promising approach to overcome the DIM physicochemical limitations and potentialize its biological properties.

Preconditioning with lipopolysaccharide (LPS) or opioid antagonists has a neuroprotective effect in ischemic insults. However, the co‑preconditioning effect of toll‑like receptor ligands and opioid antagonists has not been investigated. In this study we examined the neuroprotective effect of LPS and naltrexone (NTX) preconditioning and co‑preconditioning in unilateral selective hippocampal ischemia in rats to assess for possible synergistic protective effects. LPS and NTX were injected unilaterally into the left cerebral ventricle of male rats. Forty‑eight hours after LPS and twenty‑four hours after NTX injection, ipsilateral selective hippocampal ischemia was induced using a modified version of the photothrombotic method. Protective effects for LPS and NTX were assessed by evaluating infarct volume (using 2,3,5‑triphenyltetrazolium chloride staining), and cognitive function (using radial arm water maze and passive avoidance tests). Animals in the ischemic group had an infarct lesion and considerable cognitive impairment, compared with the sham group. LPS or NTX preconditioning significantly reduced the infarct size and improved cognitive function. Moreover, co‑preconditioning with LPS and NTX increased the protective effect compared with preconditioning with LPS or NTX alone. Our data showed that LPS and NTX preconditioning resulted in a neuroprotective effect in hippocampal ischemia. Furthermore, co‑preconditioning with LPS and NTX resulted in a synergistic protective effect.

Retinal pigment epithelium (RPE) is an important part of the blood-retina barrier (BRB) that separates the retina from the choroid. Although melanin granules contribute to the mechanical stability of the BRB complex, it is unknown if the age pigment lipofuscin affects mechanical properties of the tissue. To address this issue the effect of sub-lethal photic stress mediated by phagocytized lipofuscin granules, isolated from RPE of human donors, on morphology and mechanical properties of ARPE-19 cells was investigated. Nanomechanical analysis using atomic force spectroscopy revealed that irradiation of cells containing lipofuscin granules with blue light induced significant softening of the cells, which was accompanied by substantial reorganization of the cell cytoskeleton due to peroxidation of cellular proteins. Our results indicate that lipofuscin-mediated photic stress can cause significant modification of the RPE cells with the potential to disturb biological function of the BRB complex.

Numerous studies have focused on the deteriorate role of amyloid-β (Aβ) on retina, implying the potential pathogenic mechanism underlying age-related macular degeneration (AMD). However, the mechanism underlying the Aβ deposition in AMD patients remains unknown. Beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1), rate-limiting enzyme for Aβ production, plays an important role in Aβ deposition in the brain. In the current study, we aimed to clarify the regulation mechanism of BACE1 and explore potential drug targets using a lipofuscinfluorophore A2E-mediated photo-oxidation model. In this model, Aβ 1-40 and Aβ 1-42 levels increased simultaneously with the enhanced BACE1 expression. These changes were associated with the hypomethylation of specific loci within the BACE1 gene promoter and the decreased levels of DNA methyltransferase 1 (DNMT1). Furthermore, we noticed overlapping regions of differentially methylated CpG islands and specificity protein (Sp1) binding sites within the BACE1 promoter. We employed chromatin immunoprecipitation (ChIP) assay to verify that the decreased BACE1 promoter methylation by DNMT1 enabled increased binding between Sp1 and the BACE1 promoter, which further enhanced BACE1 transcription. The inhibition of Sp1 with mithramycin A (MTM) could down-regulate the expression of BACE1 as well as alleviate the RPE barrier morphology and function impairment. Our results for the first time show the competitive regulation of BACE1 by transcription factor Sp1 and DNMT1 after photo-oxidation and confirm the potential novel protective role of MTM on RPE cells., (Copyright © 2018. Published by Elsevier Ltd.)

Enhanced sensitivity to light (photophobia) and patterns is common in migraine and can be regarded as visual allodynia. We aimed to develop and validate a questionnaire to easily quantify sensitivity to light and patterns in large populations, and to assess and compare visual allodynia across different migraine subtypes and states. We developed the Leiden Visual Sensitivity Scale (L-VISS), a 9-item scale (score range 0-36 points), based on literature and patient interviews, and examined its construct validity. Furthermore, we assessed ictal and interictal visual sensitivity in episodic migraine with (n = 67) and without (n = 66) aura and chronic migraine with (n = 20) and without (n = 19) aura, and in healthy controls (n = 86). Differences between migraine subtypes and states were tested using a linear mixed model with 3 fixed factors (episodic/chronic, with/without aura, and ictal/interictal). Test-retest reliability and construct validity of L-VISS were good. Leiden Visual Sensitivity Scale scores correlated in the expected direction with light discomfort (Kendall's τ = -0.25) and pattern glare tests (τ = 0.35). Known-group comparisons confirmed its construct validity. Within migraine subtypes, L-VISS scores were higher in migraine with aura versus without aura and in chronic versus episodic migraine. The linear mixed model showed all factors affected the outcome (P < 0.001). The L-VISS is an easy-to-use scale to quantify and monitor the burden of bothersome visual sensitivity to light and patterns in large populations. There are remarkable ictal and interictal differences in visual allodynia across migraine subtypes, possibly reflecting dynamic differences in cortical excitability.

Background: Proper patterning of dendritic and axonal arbors is a critical step in the formation of functional neuronal circuits. Developing circuits rely on an array of molecular cues to shape arbor morphology, but the underlying mechanisms guiding the structural formation and interconnectivity of pre- and postsynaptic arbors in real time remain unclear. Here we explore how Down syndrome cell adhesion molecule (DSCAM) differentially shapes the dendritic morphology of central neurons and their presynaptic retinal ganglion cell (RGC) axons in the developing vertebrate visual system., Methods: The cell-autonomous role of DSCAM, in tectal neurons and in RGCs, was examined using targeted single-cell knockdown and overexpression approaches in developing Xenopus laevis tadpoles. Axonal arbors of RGCs and dendritic arbors of tectal neurons were visualized using real-time in vivo confocal microscopy imaging over the course of 3 days., Results: In the Xenopus visual system, DSCAM immunoreactivity is present in RGCs, cells in the optic tectum and the tectal neuropil at the time retinotectal synaptic connections are made. Downregulating DSCAM in tectal neurons significantly increased dendritic growth and branching rates while inducing dendrites to take on tortuous paths. Overexpression of DSCAM, in contrast, reduced dendritic branching and growth rate. Functional deficits mediated by tectal DSCAM knockdown were examined using visually guided behavioral assays in swimming tadpoles, revealing irregular behavioral responses to visual stimulus. Functional deficits in visual behavior also corresponded with changes in VGLUT/VGAT expression, markers of excitatory and inhibitory transmission, in the tectum. Conversely, single-cell DSCAM knockdown in the retina revealed that RGC axon arborization at the target is influenced by DSCAM, where axons grew at a slower rate and remained relatively simple. In the retina, dendritic arbors of RGCs were not affected by the reduction of DSCAM expression., Conclusions: Together, our observations implicate DSCAM in the control of both pre- and postsynaptic structural and functional connectivity in the developing retinotectal circuit, where it primarily acts as a neuronal brake to limit and guide postsynaptic dendrite growth of tectal neurons while it also facilitates arborization of presynaptic RGC axons cell autonomously.

Motor cortex (M1) lesions result in motor impairments, yet how M1 contributes to the control of movement remains controversial. To investigate the role of M1 in sensory guided motor coordination, we trained mice to navigate a virtual corridor using a spherical treadmill. This task required directional adjustments through spontaneous turning, while unexpected visual offset perturbations prompted induced turning. We found that M1 is essential for execution and learning of this visually guided task. Turn-selective layer 2/3 and layer 5 pyramidal tract (PT) neuron activation was shaped differentially with learning but scaled linearly with turn acceleration during spontaneous turns. During induced turns, however, layer 2/3 neurons were activated independent of behavioral response, while PT neurons still encoded behavioral response magnitude. Our results are consistent with a role of M1 in the detection of sensory perturbations that result in deviations from intended motor state and the initiation of an appropriate corrective response., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Motion sickness is thought to occur when the brain's assumptions about incoming sensory information do not match the actual signals received. These signals must involve the vestibular system for motion sickness to occur. In this paper, we describe an experiment in which subjects experienced unexpected visual motions, or perturbations, as they navigated a virtual environment (VE) while standing and wearing a head mounted display (HMD) or while viewing a monitor. We found that postural instability, as measured by a balance board, increased with time only when perturbations were present. HMD users exhibited greater sway when exposed to visual perturbations than did monitor users. Yet motion sickness increased only when an HMD was used and occurred with or without participants undergoing perturbations. These results suggest that the postural instability which is generated by unexpected visual perturbation does not necessarily increase the likelihood of motion sickness in a virtual environment., (Published by Elsevier Ltd.)

Fear of snakes and spiders are common animal phobias. Emotion regulation can change the response to emotional stimuli, including snakes and spiders. It is well known that emotion regulation modulates the late positive potential (LPP), which reflects sustained motivated attention. However, research concerning the effect of emotion regulation on the early posterior negativity (EPN), which reflects early selective attention, is scarce. The present research question was whether the EPN and LPP amplitudes are modulated by regulation of emotional responses to snake and spider stimuli. Emotion up- and down-regulation were expected to enhance and reduce the LPP amplitude, respectively, but emotion regulation was not expected to modulate the EPN amplitude. Female participants passively viewed snake, spider, and bird pictures, and up- and down-regulated their emotional responses to the snake and spider pictures using self-focused reappraisal, while their electroencephalogram was recorded. There were EPNs for snakes and spiders vs. birds, as well as for snakes vs. spiders. The LPP amplitude tended to be enhanced for snakes and spiders compared to birds. Most importantly, the LPP amplitude was larger in the up-regulate than in the down-regulate condition for both snakes and spiders, but there was no evidence that the EPN amplitude was modulated by emotion regulation. This suggests that emotion regulation modulated sustained motivated attention, but not early selective attention, to snakes and spiders. The findings are in line with the notion that the emotional modulation of the EPN is more automatic than the emotional modulation of the LPP., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Visual stimuli are often used for obsessive-compulsive (OC) symptom provocation in research studies. We tested the induction of anxiety and OC checking symptoms across different types of checking provocation stimuli in three populations: individuals with obsessive compulsive disorder (OCD), individuals with checking symptoms but without a diagnosis of OCD, and control individuals with neither checking symptoms nor a clinical diagnosis. One set of provocative images depicted objects that are commonly associated with checking anxiety. Another set ('enhanced provocative images') depicted similar objects but also included contextual cues suggesting a specific harmful scenario that could occur. As expected, the enhanced provocative images were more effective at inducing anxiety and OC symptoms than the standard provocative images. Future studies requiring checking symptom provocation should therefore consider incorporating similarly suggestive images. Individuals with clinical OCD reported the greatest provocation in response to these images, followed by those with nonclinical checking, followed by control individuals. Thus, these stimuli are able to provoke OC checking symptoms and anxiety differentially across groups, with the intensity of provocation reflecting diagnostic status. All groups demonstrated a similar qualitative pattern of provocation across images. Finally, in all groups, reported anxiety closely tracked intrusive thoughts and checking urges., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We assessed the neuroprotective effects of Lycium barbarum Polysaccharides (LBP) on photoreceptor degeneration and the mechanisms involved in oxidative stress in light-exposed mouse retinas. Mice were given a gavage of LBP (150 mg/kg or 300 mg/kg) or phosphate buffered saline (PBS) for 7 days before exposure to light (5000 lx for 24 h). We found that LBP significantly improved the electroretinography (ERG) amplitudes of the a- and b-waves that had been attenuated by light exposure. In addition, changes caused by light exposure including photoreceptor cell loss, nuclear condensation, an increased number of mitochondria vacuoles, outer membrane disc swelling and cristae fractures were distinctly ameliorated by LBP. LBP treatment also significantly prevented the generation of reactive oxygen species (ROS) compared with PBS treatment. The levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and thioredoxin reductase (TrxR1) mRNA were decreased in PBS-treated mice compared with controls but increased remarkably in LBP-treated mice. The mRNA levels of the DNA repair gene Poly (ADP-ribose) polymerase (PARP14) was increased in PBS-treated mice but decreased significantly in the LBP-treated mice. Our findings indicate that pretreatment with LBP effectively protected photoreceptor cells against light-induced retinal damage probably through the up-regulation of the antioxidative genes Nrf2 and TrxR1, the elimination of oxygen free radicals, and the subsequent reduction in the mitochondrial reaction to oxidative stress and enhancement in antioxidant capacity. In addition, the decreased level of PARP14 mRNA in LBP-treated mice also indicated a protective effect of LBP on delaying photoreceptor in the light-damaged retina., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: How experience and individuality shape action selection remains a major question in neuroscience. Visually-evoked escape behavior within Drosophila melanogaster provides a robust model to study these mechanisms within neural circuits but requires novel assays to circumvent limitations of current behavior assays., Method: Here we describe and characterize a simple, low to moderate cost, and flexible assay for studying visually-evoked escape responses in tethered flies. This assay consists of a DLP projector, cylindrical rear projection screen, and an automated flight interruption motor all controlled within a MATLAB environment., Results: We find this assay effectively recapitulates fly behaviors previously observed in free behavior assays, and provides a novel opportunity to investigate the behavior of individual flies over the course of numerous stimulus presentations., Comparison to Existing Methods: Current Drosophila escape assays do not permit multiple stimulus presentations and can be highly complex and expensive to implement., Conclusions: This assay provides an effective system to further identify neural components and mechanisms underlying action selection within parallel sensorimotor pathways., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Visually induced motion sickness (VIMS) is a common discomfort response associated with vection-provoking stimuli. It has been suggested that susceptibility to VIMS depends on the ability to regulate visual performance during vection. To test this, 29 participants, with VIMS susceptibility assessed by Motion Sickness Susceptibility Questionnaire, were recruited to undergo three series of sustained attention to response tests (SARTs) while watching dot pattern stimuli known to provoke roll-vection. In general, SARTs performance was impaired in the central visual field (CVF), but improved in peripheral visual field (PVF), suggesting the reallocation of attention during vection. Moreover, VIMS susceptibility was negatively correlated with the effect sizes, suggesting that participants who were less susceptible to VIMS showed better performance in attention re-allocation. Finally, when trained to re-allocation attention from the CVF to the PVF, participants experienced more stable vection. Findings provide a better understanding of VIMS and shed light on possible preventive measures. Practitioner Summary: Allocating less visual attention to central visual field during visual motion stimulation is associated with stronger vection and higher resistance to motion sickness. Virtual reality application designers may utilise the location of visual tasks to strengthen and stabilise vection, while reducing the potential of visually induced motion sickness.

Introduction: Photosensitivity, which is a main feature of Jeavons syndrome, can be seen in other types of idiopathic or genetic epilepsies with focal or generalized seizures and tends to disappear spontaneously usually in the second decade. Although it responds well to antiepileptic treatment, especially to valproic acid, it may continue into adulthood in rare cases., Case Report: We describe a 63-year-old male patient with eyelid myoclonia with absences, generalized tonic-clonic seizures, and severe photosensitivity accompanied by eyelid myoclonia. Seizures were treated with antiepileptic treatment, whereas photosensitivity still continued on electroencephalogram without clinical findings., Conclusion: Our elderly patient with Jeavons syndrome with ongoing remarkable photosensitivity demonstrated that it may continue to older ages, although it is uncommon.

Purpose: To develop an objective psychophysical method to quantify light-induced visual discomfort, and to measure the effects of viewing condition and stimulus wavelength., Methods: Eleven visually normal subjects participated in the study. Their pupils were dilated (2.5% phenylephrine) before the experiment. A Ganzfeld system presented either red (1.5, 19.1, 38.2, 57.3, 76.3, 152.7, 305.3 cd/m2) or blue (1.4, 7.1, 14.3, 28.6, 42.9, 57.1, 71.4 cd/m2) randomized light intensities (1 s each) in four blocks. Constant white-light stimuli (3 cd/m2, 4 s duration) were interleaved with the chromatic trials. Participants reported each stimulus as either "uncomfortably bright" or "not uncomfortably bright." The experiment was done binocularly and monocularly in separate sessions, and the order of color/viewing condition sequence was randomized across participants. The proportion of "uncomfortable" responses was used to generate individual psychometric functions, from which 50% discomfort thresholds were calculated., Results: Light-induced discomfort was higher under blue compared with red light stimulation, both during binocular (t(10) = 3.58, P < 0.01) and monocular viewing (t(10) = 3.15, P = 0.01). There was also a significant difference in discomfort between viewing conditions, with binocular viewing inducing more discomfort than monocular viewing for blue (P < 0.001), but not for red light stimulation., Conclusions: The light-induced discomfort characteristics reported here are consistent with features of the melanopsin-containing intrinsically photosensitive retinal ganglion cell light irradiance pathway, which may mediate photophobia, a prominent feature in many clinical disorders. This is the first psychometric assessment designed around melanopsin spectral properties that can be customized further to assess photophobia in different clinical populations.

The vestibulo-ocular reflex (VOR) adaptation is an ideal model for investigating how the neurosteroid 17 beta-estradiol (E2) contributes to the modification of behavior by regulating synaptic activities. We hypothesized that E2 impacts VOR adaptation by affecting cerebellar synaptic plasticity at the parallel fiber-Purkinje cell (PF) synapse. To verify this hypothesis, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in adaptation of the VOR in male rats using an oral dose (2.5 mg/kg) of the aromatase inhibitor letrozole. We also assessed the effect of letrozole on synaptic plasticity at the PF synapse in vitro, using cerebellar slices from male rats. We found that letrozole acutely impaired both gain increases and decreases adaptation of the VOR without altering basal ocular-motor performance. Moreover, letrozole prevented long-term potentiation at the PF synapse (PF-LTP) without affecting long-term depression (PF-LTD). Thus, in male rats neurosteroid E2 has a relevant impact on VOR adaptation and affects exclusively PF-LTP. These findings suggest that E2 might regulate changes in VOR adaptation by acting locally on cerebellar and extra-cerebellar synaptic plasticity sites.

Degeneration of the human retinal pigmented epithelium (hRPE) is involved in several eye disorders such as age-related macular degeneration (AMD). In this study, we investigated the protective effect of IGF-1 on human primary cultured RPE cells and its underlying mechanism. IGF-1 dose- and time-dependently promoted the survival of RPE cells from serum deprivation. Western blot showed that IGF-1 stimulated the activation of the PI3K/Akt and MAPK pathways in hRPE. Inhibition of the PI3K/Akt pathway by the PI3K-specific inhibitor, LY294002 or inhibition of Akt by Akt-specific inhibitors Akt inhibitor VIII or SN-38, or downregulation Akt with siRNA specific for Akt blocked the effect of IGF-1 on hRPE. In contrast, blockade of the MAPK pathway with a specific inhibitor PD98059 had no effect. Interestingly, vitreous IGF-1 injection reversed the inhibitory effect of light exposure (a dry AMD model) on both a wave and b wave. Immunocytochemistry showed that vitreous IGF-1 injections promoted the survival of RPE cells in rat retina and the expression of RPE65 in RPE cells from light injury. These results indicate that IGF-1 is able to protect hRPE cell from different insults in vivo and in vitro. Further detailed studies may lead the way to a therapeutic intervention for retinal diseases in which cell death is an underlying contributory mechanism.

We examined whether the optogenetic noise-photostimulation (ONP) of the barrel cortex (BC) of anesthetized Thy1-ChR2-YFP transgenic mice increases the neuronal multiunit-activity response evoked by whisker mechanical stimulation (whisker-evoked MUA). In all transgenic mice, we found that the signal-to-noise ratio (SNR) of such whisker-evoked MUA signals exhibited an inverted U-like shape as a function of the ONP level. Numerical simulations of a ChR2-expressing neuron model qualitatively support our experimental data. These results show that the application of an intermediate intensity of ONP in the brain can increase cortical somatosensory spike responses to whisker protraction. These findings suggest that ONP of the mice-BC could produce improvements in somatosensory perception to whisker stimulation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The use of electronic devices with light-emitting screens has increased exponentially in the last decade. As a result, humans are continuously exposed to unintentional artificial light. We explored the effects of acute and chronic exposure to artificial light at night (ALAN) via screen illumination on sleep, circadian rhythms, and related functional outcomes. Nineteen participants (11 female and 8 males, mean age 28.1 ± 7.2 years) underwent a six-night study with three experimental conditions using a repeated-measures design: baseline (first night, no light exposure), acute ALAN exposure (second night), and chronic ALAN exposure (third to sixth nights). Each light exposure lasted for 2 hours (21:00-23:00). Participants underwent an overnight polysomnography at the end of each condition (nights 1, 2, and 6). We collected urine samples (for melatonin metabolite analysis), while body (oral) temperatures were measured before and after exposure. Each morning, the participants filled out questionnaires and conducted a computerized attention test. Both acute and chronic illumination significantly disrupted sleep continuity and architecture and led to greater self-reported daytime sleepiness, negative emotions, and attention difficulties. Both exposure types also altered circadian rhythms, subduing the normal nocturnal decline in body temperature and dampening nocturnal melatonin secretion. In sum, ALAN exposure from electronic screens has an immediate, detrimental, yet stable effect on sleep, circadian regulation, and next-day functional outcomes. Given the widespread use of electronic devices today, our findings suggest that even one night of screen light exposure may be sufficient to cause adverse effects on health and performance.

Transcranial direct current stimulation (tDCS) is a neuromodulatory technique which has garnered recent interest in the potential treatment for emotion-based psychopathology. While accumulating evidence suggests that tDCS may attenuate emotional vulnerability, critically, little is known about underlying mechanisms of this effect. The present study sought to clarify this by examining the possibility that tDCS may affect emotional vulnerability via its capacity to modulate attentional bias towards threatening information. Fifty healthy participants were randomly assigned to receive either anodal tDCS (2 mA/min) stimulation to the left dorsolateral prefrontal cortex (DLPFC), or sham. Participants were then eye tracked during a dual-video stressor task designed to elicit emotional reactivity, while providing a concurrent in-vivo measure of attentional bias. Greater attentional bias towards threatening information was associated with greater emotional reactivity to the stressor task. Furthermore, the active tDCS group showed reduced attentional bias to threat, compared to the sham group. Importantly, attentional bias was found to statistically mediate the effect of tDCS on emotional reactivity, while no direct effect of tDCS on emotional reactivity was observed. The findings are consistent with the notion that the effect of tDCS on emotional vulnerability may be mediated by changes in attentional bias, holding implications for the application of tDCS in emotion-based psychopathology. The findings also highlight the utility of in-vivo eye tracking measures in the examination of the mechanisms associated with DLPFC neuromodulation in emotional vulnerability., (Copyright © 2017 Elsevier Ltd. All rights reserved.)