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Purpose: Data are limited pertaining to the long‐term benefits of aflibercept treatment for neovascular age‐related macular degeneration (nAMD). The aim of this study was to provide outcomes, safety, durability and quality‐of‐life data with aflibercept using a modified treat, extend and fixed regime over 4 years. Methods: Prospective, multicentre, single cohort observational study of treatment‐naïve nAMD participants treated with aflibercept as 2‐year extension of the MATE‐trial that compared early and late Treat‐and‐Extend for 2 years. Refracted ETDRS best corrected visual acuity (BCVA), central retinal thickness (CRT), treatment interval and adverse events were assessed. Quality‐of‐life was measured using the Macular Disease Dependent Quality of Life (MacDQoL) and Macular Disease Treatment Satisfaction Questionnaires (MacTSQ). Results: Twenty‐six of 40 participants completing the MATE‐trial were enrolled with 20 completing the total 4‐year study. Mean BCVA was 60.7 at Month 0 and 64.8 ETDRS letters at Month 48 while CRT decreased from 423.7 μm to 292.2 μm. Five participants discontinued treatment due to inactivity. The mean number of treatments and visits for the remaining participants was 27 and 30.0, respectively, with treatment intervals extended to 12 weeks in four participants at Month 48. Both AMD‐specific QoL and treatment satisfaction remained stable between Months 0 and 48 and mean BCVA significantly correlated with AMD‐specific QoL scores at Months 12, 24 and 48. Conclusions: Results suggest that BCVA can be maintained over 48 months when following a treat‐extend‐and‐fix regimen of aflibercept with intervals out to 12 weeks, while maintaining AMD‐specific QoL and treatment satisfaction. [ABSTRACT FROM AUTHOR]

Mitochondrial function declines with age, and many pathological processes in neurodegenerative diseases stem from this dysfunction when mitochondria fail to produce the necessary energy required. Photobiomodulation (PBM), long‐wavelength light therapy, has been shown to rescue mitochondrial function in animal models and improve human health, but clinical uptake is limited due to uncertainty around efficacy and the mechanisms responsible. Using 31P magnetisation transfer magnetic resonance spectroscopy (MT‐MRS) we quantify, for the first time, the effects of 670 nm PBM treatment on healthy ageing human brains. We find a significant increase in the rate of ATP synthase flux in the brain after PBM in a cohort of older adults. Our study provides initial evidence of PBM therapeutic efficacy for improving mitochondrial function and restoring ATP flux with age, but recognises that wider studies are now required to confirm any resultant cognitive benefits. [ABSTRACT FROM AUTHOR]

Using event-related potentials (ERPs), we investigated the N400 (an ERP component that occurs in response to meaningful stimuli) in children aged 8-10 years old and examined relationships between the N400 and individual differences in listening comprehension, word recognition and non-word decoding. Moreover, we tested the claim that the N400 effect provides a valuable indicator of behavioural vocabulary knowledge. Eighteen children were presented with picture-word pairs that were either "congruent" (the picture depicted the spoken word) or "incongruent" (they were unrelated). Three peaks were observed in the ERP waveform triggered to the onset of the picture-word stimuli: an N100 in fronto-central channels, an N200 in central-parietal channels and an N400 in frontal, central and parietal channels. In contrast to the N100 peak, the N200 and N400 peaks were sensitive to semantic incongruency with greater peak amplitudes for incongruent than congruent conditions. The incongruency effects for each peak correlated positively with listening comprehension but when the peak amplitudes were averaged across congruent/incongruent conditions they correlated positively with non-word decoding. These findings provide neurophysiological support for the position that sensitivity to semantic context (reflected in the N400 effect) is crucial for comprehension whereas phonological decoding skill relates to more general processing differences reflected in the ERP waveform. There were no correlations between ERP and behavioural measures of expressive or receptive vocabulary knowledge for the same items, suggesting that the N400 effect may not be a reliable estimate of vocabulary knowledge in children aged 8-10 years.

Although coronavirus disease 2019 (COVID-19) affects the respiratory system, it can also have neurological consequences leading to cognitive deficits such as memory problems. The aim of our study was to assess the impact of COVID-19 on working memory function. We developed and implemented an online anonymous survey with a working memory quiz incorporating aspects of gamification to engage participants. 5428 participants successfully completed the survey and memory quiz between 8th December 2020 and 5th July 2021 (68.6% non-COVID-19 and 31.4% COVID-19). Most participants (93.3%) completed the survey and memory quiz relatively rapidly (mean time of 8.84 minutes). Categorical regression was used to assess the contribution of COVID status, age, time post-COVID (number of months elapsed since having had COVID), symptoms, ongoing symptoms and gender, followed by non-parametric statistics. A principal component analysis explored the relationship between subjective ratings and objective memory scores. The objective memory scores were significantly correlated with participants' own assessment of their cognitive function. The factors significantly affecting memory scores were COVID status, age, time post-COVID and ongoing symptoms. Our main finding was a significant reduction in memory scores in all COVID groups (self-reported, positive-tested and hospitalized) compared to the non-COVID group. Memory scores for all COVID groups combined were significantly reduced compared to the non-COVID group in every age category 25 years and over, but not for the youngest age category (18–24 years old). We found that memory scores gradually increased over a period of 17 months post-COVID-19. However, those with ongoing COVID-19 symptoms continued to show a reduction in memory scores. Our findings demonstrate that COVID-19 negatively impacts working memory function, but only in adults aged 25 years and over. Moreover, our results suggest that working memory deficits with COVID-19 can recover over time, although impairments may persist in those with ongoing symptoms. [ABSTRACT FROM AUTHOR]

Researchers are increasingly attempting to undertake electroencephalography (EEG) recordings in novel environments and contexts outside of the traditional static laboratory setting. The term “mobile EEG,” although commonly used to describe many of these undertakings, is ambiguous, since it attempts to encompass a wide range of EEG device mobility, participant mobility, and system specifications used across investigations. To provide quantitative parameters for “mobile EEG,” we developed a Categorisation of Mobile EEG (CoME) scheme based upon scoring of device mobility (D, from 0, off-body, to 5, head-mounted with no additional equipment), participant mobility (P, from 0, static, to 5, unconstrained running), system specification (S, from 4, lowest, to 20, highest), and number of channels (C) used. The CoME scheme was applied to twenty-nine published mobile EEG studies. Device mobility scores ranged from 0D to 4D, participant mobility scores from 0P to 4P, and system specification scores from 6S to 17S. The format of the scores for the four parameters is given, for example, as (2D, 4P, 17S, 32C) and readily enables comparisons across studies. Our CoME scheme enables researchers to quantify the degree of device mobility, participant mobility, and system specification used in their “mobile EEG” investigations in a standardised way. [ABSTRACT FROM AUTHOR]

Following auditory deprivation, the remaining sense of vision has shown selective enhancement in visual cognition, especially in the area of near peripheral vision. Visual acuity is poor in the far periphery and may be an area where sound confers the greatest advantage in hearing persons. Experience with a visuospatial language such as British Sign Language (BSL) makes additional demands on the visual system. To test the different and separable effects of deafness and use of a visuo-spatial language on far peripheral visual processing, we investigated visual reaction times (RTs) and response accuracy to visual stimuli, between 30° and 85° along the four cardinal and four inter-cardinal meridians. We used three luminances of static, briefly illuminated stimuli in visually normal adults. The cohort tested included profoundly congenitally deaf adults (N = 17), hearing fluent BSL users (N = 8) and hearing non-signing adults (N = 18). All participants were tested using a peripheral forced choice paradigm designed previously to test deaf and hearing children (Codina et al., 2011a). Deaf adults demonstrated significantly faster RTs to all far peripheral stimuli and exceeded the abilities of both signing and non-signing hearing adults. Deaf adults were significantly faster than BSL interpreters, who in turn were significantly faster than hearing non-signing adults. The differences in RT demonstrated between groups were consistent across all visual field meridians and were not localized to any one region of the visual field. There were no differences found between any groups in accuracy of detecting these static stimuli at any retinal location. Early onset auditory deprivation appears to lead to a response time visual advantage in far peripheral responses to briefly presented, static LED stimuli, especially in the right visual field. Fluency in BSL facilitates faster visuo-motor responses in the peripheral visual field, but to a lesser extent than congenital, profound deafness. [ABSTRACT FROM AUTHOR]

Introduction: Macular degeneration (MD) can cause a central visual field defect. In a previous study, we found volumetric reductions along the entire visual pathways of MD patients, possibly indicating degeneration of inactive neuronal tissue. This may have important implications. In particular, new therapeutic strategies to restore retinal function rely on intact visual pathways and cortex to reestablish visual function. Here we reanalyze the data of our previous study using surface-based morphometry (SBM) rather than voxel-based morphometry (VBM). This can help determine the robustness of the findings and will lead to a better understanding of the nature of neuroanatomical changes associated with MD. Methods: The metrics of interest were acquired by performing SBM analysis on T1-weighted MRI data acquired from 113 subjects: patients with juvenile MD (JMD; n = 34), patients with age-related MD (AMD; n = 24) and healthy age-matched controls (HC; n = 55). Results: Relative to age-matched controls, JMD patients showed a thinner cortex, a smaller cortical surface area and a lower grey matter volume in V1 and V2, while AMD patients showed thinning of the cortex in V2. Neither patient group showed a significant difference in mean curvature of the visual cortex. Discussion: The thinner cortex, smaller surface area and lower grey matter volume in the visual cortex of JMD patients are consistent with our previous results showing a volumetric reduction in their visual cortex. Finding comparable results using two rather different analysis techniques suggests the presence of marked cortical degeneration in the JMD patients. In the AMD patients, we found a thinner cortex in V2 but not in V1. In contrast to our previous VBM analysis, SBM revealed no volumetric reductions of the visual cortex. This suggests that the cortical changes in AMD patients are relatively subtle, as they apparently can be missed by one of the methods. [ABSTRACT FROM AUTHOR]

The occipital lobe contains retinotopic representations of the visual field. The representation of the central retina in early visual areas (V1-3) is found at the occipital pole. When the central retina is lesioned in both eyes by macular degeneration, this region of visual cortex at the occipital pole is accordingly deprived of input. However, even when such lesions occur in adulthood, some visually driven activity in and around the occipital pole can be observed. It has been suggested that this activity is a result of remapping of this area so that it now responds to inputs from intact, peripheral retina. We evaluated whether or not remapping of visual cortex underlies this activity. Our functional magnetic resonance imaging results provide no evidence of remapping, questioning the contemporary view that early visual areas of the adult human brain have the capacity to reorganize extensively. [ABSTRACT FROM AUTHOR]

Primary visual cortex can undergo forms of reorganization following bilateral lesions to the retinas of animals. Brain cells that originally received input from retinal tissue that was lesioned become responsive to retina that remains intact. In humans, reorganization of the primary visual cortex has been found in adult patients with congenital foveal lesions. More recent investigations of patients with macular degeneration, who acquired retinal lesions later, have yielded mixed results. In this paper we review the evidence for and characteristics of cortical reorganization in humans and animals and suggest how it might be evaluated in the context of strategies for treating retinal disease. [ABSTRACT FROM AUTHOR]

We describe a compelling demonstration of large-scale developmental reorganization in the human visual pathways. The developmental reorganization was observed in rod monochromats, a rare group of congenitally colorblind individuals who virtually lack cone photoreceptor function. Normal controls had a cortical region, spanning several square centimeters, that responded to signals initiated in the all-cone foveola but was inactive under rod viewing conditions; in rod monochromats this cortical region responded powerfully to rod-initiated signals. The measurements trace a causal pathway that begins with a genetic anomaly that directly influences sensory cells and ultimately results in a substantial central reorganization. [ABSTRACT FROM AUTHOR]

Purpose: Achromatopsia is a rare inherited disorder rendering retinal cone photoreceptors nonfunctional. As a consequence, the sizable foveal representation in the visual cortex is congenitally deprived of visual input, which prompts a fundamental question: is the cortical representation of the central visual field in patients with achromatopsia remapped to take up processing of paracentral inputs? Such remapping might interfere with gene therapeutic treatments aimed at restoring cone function., Methods: We conducted a multicenter study to explore the nature and plasticity of vision in the absence of functional cones in a cohort of 17 individuals affected by autosomal recessive achromatopsia and confirmed biallelic disease-causing CNGA3 or CNGB3 mutations. Specifically, we tested the hypothesis of foveal remapping in human achromatopsia. For this purpose, we applied two independent functional magnetic resonance imaging (fMRI)-based mapping approaches, i.e. conventional phase-encoded eccentricity and population receptive field mapping, to separate data sets., Results: Both fMRI approaches produced the same result in the group comparison of achromatopsia versus healthy controls: sizable remapping of the representation of the central visual field in the primary visual cortex was not apparent., Conclusions: Remapping of the cortical representation of the central visual field is not a general feature in achromatopsia. It is concluded that plasticity of the human primary visual cortex is less pronounced than previously assumed. A pretherapeutic imaging workup is proposed to optimize interventions.

Purpose: The aim of this study was to assess both retinal and cortical structure in a cohort of patients with long-term acquired central retinal disease in order to identify potential disease biomarkers and to explore the relationship between the anterior and posterior visual pathways., Methods: Fourteen participants diagnosed with long-term central retinal disease underwent structural assessments of the retina using spectral-domain optical coherence tomography, including macular ganglion cell layer (GCL) and peripapillary retinal nerve fiber layer (pRNFL) thickness. Structural magnetic resonance imaging was used to measure visual cortex, including cortical volume of the entire occipital lobe and cortical thickness of the occipital pole and calcarine sulcus, representing the central and peripheral retina, respectively., Results: Mean thickness was significantly reduced in both the macular GCL and the inferior temporal pRNFL across patients. Cortical thickness was significantly reduced in both the occipital pole and calcarine sulcus, representing the central and peripheral retina, respectively. Disease duration significantly correlated with GCL thickness with a large effect size, whereas a medium effect size suggests the possibility that cortical thickness in the occipital pole may correlate with visual acuity., Conclusions: Long-term central retinal disease is associated with significant structural changes to both the retina and the brain. Exploratory analysis suggests that monitoring GCL thickness may be a sensitive biomarker of disease progression and reductions in visual cortical thickness may be associated with reduced visual acuity. Although this study is limited by its heterogeneous population, larger cohort studies would be needed to better establish some of the relationships detected between disease dependent structural properties of the anterior and posterior visual pathway given the effect sizes reported in our exploratory analysis.

Autosomal recessive Achromatopsia (ACHM) is a rare inherited disorder associated with dysfunctional cone photoreceptors resulting in a congenital absence of cone input to visual cortex. This might lead to distinct changes in cortical architecture with a negative impact on the success of gene augmentation therapies. To investigate the status of the visual cortex in these patients, we performed a multi-centre study focusing on the cortical structure of regions that normally receive predominantly cone input. Using high-resolution T1-weighted MRI scans and surface-based morphometry, we compared cortical thickness, surface area and grey matter volume in foveal, parafoveal and paracentral representations of primary visual cortex in 15 individuals with ACHM and 42 normally sighted, healthy controls (HC). In ACHM, surface area was reduced in all tested representations, while thickening of the cortex was found highly localized to the most central representation. These results were comparable to more widespread changes in brain structure reported in congenitally blind individuals, suggesting similar developmental processes, i.e., irrespective of the underlying cause and extent of vision loss. The cortical differences we report here could limit the success of treatment of ACHM in adulthood. Interventions earlier in life when cortical structure is not different from normal would likely offer better visual outcomes for those with ACHM., (Copyright © 2021. Published by Elsevier Inc.)

Most individuals with congenital achromatopsia (ACHM) carry mutations that affect the retinal phototransduction pathway of cone photoreceptors, fundamental to both high acuity vision and colour perception. As the central fovea is occupied solely by cones, achromats have an absence of retinal input to the visual cortex and a small central area of blindness. Additionally, those with complete ACHM have no colour perception, and colour processing regions of the ventral cortex also lack typical chromatic signals from the cones. This study examined the cortical morphology (grey matter volume, cortical thickness, and cortical surface area) of multiple visual cortical regions in ACHM ( n = 15) compared to normally sighted controls ( n = 42) to determine the cortical changes that are associated with the retinal characteristics of ACHM. Surface-based morphometry was applied to T1-weighted MRI in atlas-defined early, ventral and dorsal visual regions of interest. Reduced grey matter volume in V1, V2, V3, and V4 was found in ACHM compared to controls, driven by a reduction in cortical surface area as there was no significant reduction in cortical thickness. Cortical surface area (but not thickness) was reduced in a wide range of areas (V1, V2, V3, TO1, V4, and LO1). Reduction in early visual areas with large foveal representations (V1, V2, and V3) suggests that the lack of foveal input to the visual cortex was a major driving factor in morphological changes in ACHM. However, the significant reduction in ventral area V4 coupled with the lack of difference in dorsal areas V3a and V3b suggest that deprivation of chromatic signals to visual cortex in ACHM may also contribute to changes in cortical morphology. This research shows that the congenital lack of cone input to the visual cortex can lead to widespread structural changes across multiple visual areas., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lowndes, Molz, Warriner, Herbik, de Best, Raz, Gouws, Ahmadi, McLean, Gottlob, Kohl, Choritz, Maguire, Kanowski, Käsmann-Kellner, Wieland, Banin, Levin, Hoffmann, Morland and Baseler.)

Is the brain able to reorganise following loss of sensory input? New work on individuals with sight loss shows that, while brain areas normally allocated to vision respond to other sensory stimuli, those responses are unlikely to mean the brain has rewired., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Previous research has shown atrophy of visual cortex can occur in retinotopic representations of retinal lesions resulting from eye disease. However, the time course of atrophy cannot be established from these cross-sectional studies, which included patients with longstanding disease of varying severity. Our aim, therefore, was to measure visual cortical structure over time in participants after onset of unilateral visual loss resulting from AMD., Methods: Inclusion criteria were onset of acute unilateral neovascular AMD with bilateral dry AMD based on clinical examination. Therefore, substantial loss of unilateral visual input to cortex was relatively well-defined in time. Changes in cortical anatomy were assessed in the occipital lobe as a whole, and in cortical representations of the lesion and intact retina, the lesion and intact projection zones, respectively. Whole brain, T1-weighted magnetic resonance imaging was taken at diagnosis (before antiangiogenic treatment to stabilize the retina), during the 3- to 4-month initial treatment period, with a long-term follow-up approximately 5 (range 3.8-6.1 years) years later., Results: Significant cortical atrophy was detected at long-term follow-up only, with a reduction in mean cortical volume across the whole occipital lobe. Importantly, this reduction was explained by cortical thinning of the lesion projection zone, which suggests additional changes to those associated with normal aging. Over the period of study, antiangiogenic treatment stabilized visual acuity and central retinal thickness, suggesting that the atrophy detected was most likely governed by long-term decreased visual input., Conclusions: Our results indicate that consequences of eye disease on visual cortex are atrophic and retinotopic. Our work also raises the potential to follow the status of visual cortex in individuals over time to inform on how best to treat patients, particularly with restorative techniques.

Purpose: To assess cortical responses in patients undergoing antiangiogenic treatment for wet age-related macular degeneration (AMD) using functional magnetic resonance imaging (fMRI) as an objective, fixation-independent measure of topographic visual function., Methods: A patient with bilateral neovascular AMD was scanned using fMRI before and at regular intervals while undergoing treatment with intravitreal antiangiogenic injections (ranibizumab). Blood oxygenation level-dependent signals were measured in the brain while the patient viewed a stimulus consisting of a full-field flickering (6 Hz) white light alternating with a uniform gray background (18 s on and 18 s off). Topographic distribution and magnitude of activation in visual cortex were compared longitudinally throughout the treatment period (<1 year) and with control patients not currently undergoing treatment. Clinical behavioral tests were also administered, including visual acuity, microperimetry, and reading skills., Results: The area of visual cortex activated increased significantly after the first treatment to include more posterior cortex that normally receives inputs from lesioned parts of the retina. Subsequent treatments yielded no significant further increase in activation area. Behavioral measures all generally showed an improvement with treatment but did not always parallel one another. The untreated control patient showed a consistent lack of significant response in the cortex representing retinal lesions., Conclusions: Retinal treatments may not only improve vision but also result in a concomitant improvement in fixation stability. Current clinical behavioral measures (e.g., acuity and perimetry) are largely dependent on fixation stability and therefore cannot separate improvements of visual function from fixation improvements. fMRI, which provides an objective and sensitive measure of visual function independent of fixation, reveals a significant increase in visual cortical responses in patients with wet AMD after treatment with antiangiogenic injections. Despite recent evidence that visual cortex degenerates subsequent to retinal lesions, our results indicate that it can remain responsive as its inputs are restored.