Explore the vast range of titles available.

Background Multifocal visual evoked potential (MF-VEP) assesses a wider visual field than full-field VEP (FF-VEP) and potentially offers a more precise analysis of optic nerve injury and repair following optic neuritis. MF-VEP may offer advantages over FF-VEP as an endpoint in clinical trials of remyelinating therapies. Objective MF-VEP testing was used to study changes in visual pathways in 48% of RENEW [phase II, opicinumab (anti-LINGO-1; BIIB033) vs. placebo after first acute unilateral optic neuritis] participants. Methods This exploratory MF-VEP RENEW substudy compared mean outcomes at weeks 24 and 32 among participants in the intent-to-treat (ITT; n  = 39; 72% female; mean age: 32.3 years) and per-protocol (PP; n  = 31; 71% female; mean age: 32.2 years) populations in affected and fellow eye latency from fellow eye baseline latency and affected and fellow eye amplitude from their own baselines. Treatment differences were evaluated using analysis of covariance (week 24) and a mixed-effect model of repeated measures (week 32). Last observation carried forward was used to impute missing data at week 24. Results A trend for improvement in affected eye MF-VEP latency with opicinumab versus placebo was seen in the ITT and PP populations at weeks 24 and 32. Both treatment groups in the ITT population experienced partial recovery of amplitude in the affected eye at week 32. Notably, the mean change in fellow eye amplitude at weeks 24 and 32 was − 17.57 and − 31.41 nanovolts (nV) in placebo but only − 0.59 and 1.93 nV in the opicinumab group [differences at weeks 24 and 32: 16.98 nV ( p  = 0.050) and 33.33 nV ( p  < 0.01), respectively]. Conclusion Results from this substudy showed advantages of MF-VEP over FF-VEP in multicenter studies of central nervous system reparative therapies and provide novel evidence that fellow eye visual pathway amplitude loss occurs after optic neuritis but can potentially be prevented by opicinumab treatment. Registration ClinicalTrials.gov identifier NCT01721161.

•N, N-dimethyltryptamine (DMT), a psychedelic tryptamine acting on 5-HT2A serotonin receptors induces perceptual distortions in visual space.•Inhaled DMT induces strong perceptual effects as shown by the Hallucinogen Rating Scale.•Inhaled DMT leads to increases in visual population receptive field sizes in V1. N, N-dimethyltryptamine (DMT) is a psychedelic tryptamine acting on 5-HT2A serotonin receptors, which is associated with intense visual hallucinatory phenomena and perceptual changes such as distortions in visual space. The neural underpinnings of these effects remain unknown. We hypothesised that changes in population receptive field (pRF) properties in the primary visual cortex (V1) might underlie visual perceptual experience. We tested this hypothesis using magnetic resonance imaging (MRI) in a within-subject design. We used a technique called pRF mapping, which measures neural population visual response properties and retinotopic maps in early visual areas. We show that in the presence of visual effects, as documented by the Hallucinogen Rating Scale (HRS), the mean pRF sizes in V1 significantly increase in the peripheral visual field for active condition (inhaled DMT) compared to the control. Eye and head movement differences were absent across conditions. This evidence for short-term effects of DMT in pRF may explain perceptual distortions induced by psychedelics such as field blurring, tunnel vision (peripheral vision becoming blurred while central vision remains sharp) and the enlargement of nearby visual space, particularly at the visual locations surrounding the fovea. Our findings are also consistent with a mechanistic framework whereby gain control of ongoing and evoked activity in the visual cortex is controlled by activation of 5-HT2A receptors.

Genetically encoded optical neuromodulators create an opportunity for circuit-specific intervention in neurological diseases. One of the diseases most amenable to this approach is retinal degeneration, where the loss of photoreceptors leads to complete blindness. To restore photosensitivity, we genetically targeted a light-activated cation channel, channelrhodopsin-2, to second-order neurons, ON bipolar cells, of degenerated retinas in vivo in the Pde6b rd1 (also known as rd1 ) mouse model. In the absence of 'classical' photoreceptors, we found that ON bipolar cells that were engineered to be photosensitive induced light-evoked spiking activity in ganglion cells. The rescue of light sensitivity was selective to the ON circuits that would naturally respond to increases in brightness. Despite degeneration of the outer retina, our intervention restored transient responses and center-surround organization of ganglion cells. The resulting signals were relayed to the visual cortex and were sufficient for the animals to successfully perform optomotor behavioral tasks.

Here the authors report that repeated presentations of a visual sequence over a course of days causes evoked response potentiation in mouse V1 that is highly specific for stimulus order and timing. After V1 is trained to recognize a sequence, cortical activity regenerates the full sequence even when individual stimulus elements are omitted. Learning to recognize and predict temporal sequences is fundamental to sensory perception and is impaired in several neuropsychiatric disorders, but little is known about where and how this occurs in the brain. We discovered that repeated presentations of a visual sequence over a course of days resulted in evoked response potentiation in mouse V1 that was highly specific for stimulus order and timing. Notably, after V1 was trained to recognize a sequence, cortical activity regenerated the full sequence even when individual stimulus elements were omitted. Our results advance the understanding of how the brain makes 'intelligent guesses' on the basis of limited information to form visual percepts and suggest that it is possible to study the mechanistic basis of this high-level cognitive ability by studying low-level sensory systems.

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.

Restoring vision in inherited retinal degenerations remains an unmet medical need. In mice exhibiting a genetically engineered block of the visual cycle, vision was recently successfully restored by oral administration of 9-cis-retinyl acetate (QLT091001). Safety and visual outcomes of a once-daily oral dose of 40 mg/m2/day QLT091001 for 7 consecutive days was investigated in an international, multi-center, open-label, proof-of-concept study in 18 patients with RPE65- or LRAT-related retinitis pigmentosa. Eight of 18 patients (44%) showed a ≥20% increase and 4 of 18 (22%) showed a ≥40% increase in functional retinal area determined from Goldmann visual fields; 12 (67%) and 5 (28%) of 18 patients showed a ≥5 and ≥10 ETDRS letter score increase of visual acuity, respectively, in one or both eyes at two or more visits within 2 months of treatment. In two patients who underwent fMRI, a significant positive response was measured to stimuli of medium contrast, moving, pattern targets in both left and right hemispheres of the occipital cortex. There were no serious adverse events. Treatment-related adverse events were transient and the most common included headache, photophobia, nausea, vomiting, and minor biochemical abnormalities. Measuring the outer segment length of the photoreceptor layer with high-definition optical coherence tomography was highly predictive of treatment responses with responders having a significantly larger baseline outer segment thickness (11.7 ± 4.8 μm, mean ± 95% CI) than non-responders (3.5 ± 1.2 μm). This structure-function relationship suggests that treatment with QLT091001 is more likely to be efficacious if there is sufficient photoreceptor integrity. ClinicalTrials.gov NCT01014052.

Anesthetics are widely used in electrophysiological tests to assess retinal and visual system functions to avoid experimental errors caused by movement and stress in experimental animals. To determine the most suitable anesthetic for visual electrophysiological tests, excluding ketamine and chloral hydrate due to regulatory and side effect concerns, this study investigated the effects of ethyl carbamate (EC), avertin (AR), and pentobarbital sodium (PS) on visual signal conduction in the retina and primary visual cortex. Assessments included flash electroretinogram (FERG), pattern electroretinogram (PERG), pattern visual evoked potentials (PVEP), and flash visual evoked potentials (FVEP), FERG and FVEP were used to evaluate the responses of the retina and visual cortex to flash stimuli, respectively, while PERG and PVEP assessed responses to pattern stimuli. The research showed that AR demonstrates the least disruption to the visual signal pathway, as evidenced by consistently high characteristic peaks in the AR group across various tests. In contrast, mice given EC exhibited the lowest peak values in both FERG and FVEP, while subjects anesthetized with PS showed suppressed oscillatory potentials and PERG responses. Notably, substantial PVEP characteristic peaks were observed only in mice anesthetized with AR. Consequently, among the three anesthetics tested, AR is the most suitable for visual electrophysiological studies.

Background Preclinical trials have shown beneficial effects of nerve growth factor (NGF) administration on visual function in animal models of retinitis pigmentosa (RP). The aim of this pilot study was to explore the potential efficacy of short term NGF eye drops treatment in patients affected by RP. Methods The trial consisted in 10 days daily administration of murine NGF as eye-drops for a total dose of 1 mg NGF/pt. Eight RP patients at an advanced stage of the disease were included in the trial. To monitor safety and potential adverse effects subjects underwent standard clinical measures and were requested to report any general or topic alterations following NGF assumption. Retinal function was assessed at baseline and after treatment by best-corrected visual acuity measurement (BCVA), macular focal electroretinogram (fERG) recording and Goldmann visual field testing. Results A transient tolerable local corneal irritation was the only adverse effect reported. fERG and BCVA remained within the limits determined by test–retest analysis of a large cohort of RP patients. Three patients reported a subjective feeling of improved visual performance. This was associated to a temporary enlargement of the visual field in all three patients and to improved fERG in two of the three. Conclusions Short-term administration of NGF eye-drops caused neither significant adverse effects nor visual function losses in the tested RP patients. A minority of patients experienced an improvement of visual performance as shown by Goldmann visual field and fERG. This study supports the safety and possible efficacy of NGF eye-drops administration in RP patients. Trial registration: EudraCT n. 2008-004561-26

•Cannabis is thought to modulate GABAergic interneuronal signaling in the cortex.•GABAergic networks support cortical gamma oscillations and functional connectivity.•MEG based visual entrainment tasks were used to probe gamma circuit integrity.•Gamma oscillations in early visual cortex remain intact with regular cannabis use.•Higher-order gamma functional connectivity was disrupted in those who use cannabis. Cannabis is a widely-used illicit substance in the United States, and heavy cannabis use has been linked to deficits across multiple cognitive domains. Mechanistically, cannabis affects endocannabinoid receptors densely distributed among GABAergic interneurons throughout the cortex and cerebellum. Such interneuronal networks are known to be crucial in the generation of fast neural gamma-band responses, which support perceptual and cognitive processing and have been frequently implicated in cannabis use. However, studies to date have tended to focus on higher-order processing supported by gamma oscillations, with limited work examining more fundamental aspects of gamma circuit integrity. Herein, 84 adults who regularly use cannabis and 90 demographically-matched nonusers underwent high-density magnetoencephalography during a visual entrainment task involving three gamma-band flicker frequencies (32, 40, and 48 Hz). The resulting data were imaged in the time-frequency domain and the dynamic neural time series were extracted and tested for effects of hemisphere, frequency, and group, and then used to compute whole-brain dynamic functional connectivity. Our results indicated strong gamma entrainment in the bilateral primary visual cortices (V1), with 32 Hz responses being the strongest across both groups (p < .001) and right V1 activity being stronger than left across groups and frequencies (p = .002). Additionally, there were group-by-condition interactions in connectivity maps (p < .005), with the cannabis group having elevated 32 Hz connectivity between V1 and higher-order visual regions relative to controls. These findings suggest that basic gamma circuitry remains intact despite heavy cannabis use, while gamma functional connectivity is preferentially affected and this may lead to the higher-order deficits.

Multiple sclerosis is a degenerative inflammatory disease of the CNS characterised by immune-mediated destruction of myelin and progressive neuroaxonal loss. Myelin in the CNS is a specialised extension of the oligodendrocyte plasma membrane and clemastine fumarate can stimulate differentiation of oligodendrocyte precursor cells in vitro, in animal models, and in human cells. We aimed to analyse the efficacy and safety of clemastine fumarate as a treatment for patients with multiple sclerosis. We did this single-centre, 150-day, double-blind, randomised, placebo-controlled, crossover trial (ReBUILD) in patients with relapsing multiple sclerosis with chronic demyelinating optic neuropathy on stable immunomodulatory therapy. Patients who fulfilled international panel criteria for diagnosis with disease duration of less than 15 years were eligible. Patients were randomly assigned (1:1) via block randomisation using a random number generator to receive either clemastine fumarate (5·36 mg orally twice daily) for 90 days followed by placebo for 60 days (group 1), or placebo for 90 days followed by clemastine fumarate (5·36 mg orally twice daily) for 60 days (group 2). The primary outcome was shortening of P100 latency delay on full-field, pattern-reversal, visual-evoked potentials. We analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT02040298. Between Jan 1, 2014, and April 11, 2015, we randomly assigned 50 patients to group 1 (n=25) or group 2 (n=25). All patients completed the study. The primary efficacy endpoint was met with clemastine fumarate treatment, which reduced the latency delay by 1·7 ms/eye (95% CI 0·5–2·9; p=0·0048) when analysing the trial as a crossover. Clemastine fumarate treatment was associated with fatigue, but no serious adverse events were reported. To our knowledge, this is the first randomised controlled trial to document efficacy of a remyelinating drug for the treatment of chronic demyelinating injury in multiple sclerosis. Our findings suggest that myelin repair can be achieved even following prolonged damage. University of California, San Francisco and the Rachleff Family.