Steady-State Contrast Response Functions Provide a Sensitive and Objective Index of Amblyopic Deficits

Purpose. Visual deficits in amblyopia are neural in origin, yet are difficult to characterize with functional magnetic resonance imagery (fMRI). Our aim was to develop an objective electroencephalography (EEG) paradigm that can be used to provide a clinically useful index of amblyopic deficits. Methods. We used steady-state visual evoked potentials (SSVEPs) to measure full contrast response functions in both amblyopic (n = 10, strabismic or mixed amblyopia, mean age: 44 years) and control (n = 5, mean age: 31 years) observers, both with and without a dichoptic mask. Results. At the highest target contrast, the ratio of amplitudes across the weaker and stronger eyes was highly correlated (r = 0.76) with the acuity ratio between the eyes. We also found that the contrast response function in the amblyopic eye had both a greatly reduced amplitude and a shallower slope, but that surprisingly dichoptic masking was weaker than in controls. The results were compared with the predictions of a computational model of amblyopia and suggest a modification to the model whereby excitatory (but not suppressive) signals are attenuated in the amblyopic eye. Conclusions. We suggest that SSVEPs offer a sensitive and objective measure of the ocular imbalance in amblyopia and could be used to assess the efficacy of amblyopia therapies currently under development

Similarities and differences between behavioral and electrophysiological visual acuity thresholds in healthy infants during the second half of the first year of life

Purpose Behavioral and electrophysiological methods for visual acuity estimation typically correlate well in children and adult populations, but this relationship remains unclear in infants, particularly during the second half of the first year of life. It has been suggested that the agreement between both methods mostly relies on age and/or subjective acuity factors. The present study aimed at comparing acuity thresholds obtained with both approaches in a sample of healthy infants in a relatively narrow age range, that is 6–10 months old. Methods Acuity thresholds were assessed in 61 healthy infants aged between 6 and 10 months using the Teller acuity cards (TAC) and sweep visual evoked potentials (sVEP). The TAC stimuli (stationary vertical gratings displayed on laminated cards) ranged from 0.31 to 38 cycles per degree (cpd). The TAC acuity threshold was estimated according to the highest spatial frequency scored by the experimenter as seen by the infant. The sVEP stimuli (high-contrast vertical gratings counter-phased at 12 reversals/s) ranged from 13.5 to 1 cpd. sVEP were recorded at Oz and acuity threshold was estimated using regression linear fitting. Results Considering the entire sample, sVEP acuity thresholds (8.97 ± 2.52 cpd) were significantly better than TAC scores (5.58 ± 2.95 cpd), although the difference was within 1 octave for 64% of the infants. Neither Pearson nor intra-class correlations between the two methods were significant (0.18 and 0.03, respectively). While age at assessment was not related to any dependent variable (TAC, sVEP, sVEP–TAC difference score), subjective (behavioral) acuity was found to underlie the difference between the two methods. The difference between sVEP and TAC scores decreased as a function of subjective acuity, and at the highest subjective acuity level (>10 cpd), TAC acuity slightly exceeded sVEP acuity. Conclusions The superiority of sVEP acuity often reported in the literature was evident in our infant sample when subjective acuity (TAC) was low or moderate, but not when it was high (>10 cpd). The relationship between the two estimation methods was not dependent on age, but on subjective acuity

Lutein and zeaxanthin intake during pregnancy and visual function in offspring at 11-12 years of age

Funding: This study has been funded by Instituto de Salud Carlos III through the projects “CP14/00108, PI16/00261 and PI21/00266” (Co-funded by European Regional Development Fund “A way to make Europe”). Jordi Julvez holds the Miguel Servet-II contract (CPII19/00015) awarded by the Instituto de Salud Carlos III (co-funded by the European Social Fund “Investing in your future”). This study was also funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds; PI12/01890 incl. FEDER funds; CP13/00054 incl. FEDER funds; PI15/00118 incl. FEDER funds; CP16/00128 incl. FEDER funds; PI16/00118 incl. FEDER funds; PI16/00261 incl. FEDER funds; PI17/01340 incl. FEDER funds; PI18/00547 incl. FEDER funds), CIBERESP, Generalitat de Catalunya-CIRIT 1999SGR 00241, Generalitat de Catalunya-AGAUR (2009 SGR 501, 2014 SGR 822), Fundació La marató de TV3 (090430), Spanish Ministry of Economy and Competitiveness (SAF2012-32991 incl. FEDER funds), Agence Nationale de Securite Sanitaire de l’Alimentation de l’Environnement et du Travail (1262C0010; EST-2016 RF-21), EU Commission (261357, 308333, 603794 and 634453). We acknowledge support from the Spanish Ministry of Science and Innovation and the State Research Agency through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program.(1) Background: Lutein and zeaxanthin (L&Z) are essential dietary nutrients that are a crucial component of the human macula, contributing to visual functioning. They easily cross the placental barrier, so that retinal deposition commences during foetal development. This study aims to assess associations between maternal L&Z intake during pregnancy and offspring visual function at 11-12 years. (2) Methods: Using the Spanish INfancia y Medio Ambiente Project (INMA) Sabadell birth cohort, 431 mother-child pairs were analysed. L&Z data were obtained from food frequency questionnaires (FFQ) at week 12 and 32 of pregnancy, alongside other nutritional and sociodemographic covariates. Contrast vision (CS) and visual acuity (VA) were assessed using the automated Freiburg Acuity and Contrast Testing (FRACT) battery. Low CS and VA were defined as being below the 20th cohort centile. Associations were explored using multiple logistic regression. (3) Results: After controlling for potential confounders, L&Z intake during the 1st and 3rd trimester did not reveal any statistically significant association with either CS or VA in offspring at age 11/12 years. (4) Conclusions: No evidence of a long-term association between L&Z intake during pregnancy and visual function in offspring was found. Further larger long-term studies including blood L&Z levels are required to confirm this result.Publisher PDFPeer reviewe

Urban environment during pregnancy and childhood and white matter microstructure in preadolescence in two European birth cohorts

Growing evidence suggests that urban environment may influence cognition and behavior in children, but the underlying pollutant and neurobiological mechanisms are unclear. We evaluated the association of built environment and urban natural space indicators during pregnancy and childhood with brain white matter microstructure in preadolescents, and examined the potential mediating role of air pollution and road-traffic noise. We used data of the Generation R Study, a population-based birth cohort in Rotterdam, the Netherlands (n = 2725; 2002-2006) for the primary analyses. Replication of the main findings was attempted on an independent neuroimaging dataset from the PELAGIE birth cohort, France (n = 95; 2002-2006). We assessed exposures to 12 built environment and 4 urban natural spaces indicators from conception up to 9 years of age. We computed 2 white matter microstructure outcomes (i.e., average of fractional anisotropy (FA) and mean diffusivity (MD) from 12 white matte tracts) from diffusion tensor imaging data. Greater distance to the nearest major green space during pregnancy was associated with higher whole-brain FA (0.001 (95%CI 0.000; 0.002) per 7 m increase), and higher land use diversity during childhood was associated with lower whole-brain MD (-0.001 (95%CI -0.002; -0.000) per 0.12-point increase), with no evidence of mediation by air pollution nor road-traffic noise. Higher percentage of transport and lower surrounding greenness during pregnancy were associated with lower whole-brain FA, and road-traffic noise mediated 19% and 52% of these associations, respectively. We found estimates in the same direction in the PELAGIE cohort, although confidence intervals were larger and included the null. This study suggests an association between urban environment and white matter microstructure, mainly through road-traffic noise, indicating that greater access to green space nearby might promote white matter development

Response Inhibition and Error Monitoring during a Visual Go/No-Go Task in Inuit Children Exposed to Lead, Polychlorinated Biphenyls, and Methylmercury

Background: Lead (Pb) and polychlorinated biphenyls (PCBs) are neurotoxic contaminants that have been related to impairment in response inhibition

Neurobehavioral Function in School-Age Children Exposed to Manganese in Drinking Water

Background: Manganese neurotoxicity is well documented in individuals occupationally exposed to airborne particulates, but few data are available on risks from drinking-water exposure. Objective: We examined associations of exposure from concentrations of manganese in water and hair with memory, attention, motor function, and parent- and teacher-reported hyperactive behaviors. Methods: We recruited 375 children and measured manganese in home tap water (MnW) and hair (MnH). We estimated manganese intake from water ingestion. Using structural equation modeling, we estimated associations between neurobehavioral functions and MnH, MnW, and manganese intake from water. We evaluated exposure–response relationships using generalized additive models. Results: After adjusting for potential confounders, a 1-SD increase in log10 MnH was associated with a significant difference of –24% (95% CI: –36, –12%) SD in memory and –25% (95% CI: –41, –9%) SD in attention. The relations between log10 MnH and poorer memory and attention were linear. A 1-SD increase in log10 MnW was associated with a significant difference of –14% (95% CI: –24, –4%) SD in memory, and this relation was nonlinear, with a steeper decline in performance at MnW > 100 μg/L. A 1-SD increase in log10 manganese intake from water was associated with a significant difference of –11% (95% CI: –21, –0.4%) SD in motor function. The relation between log10 manganese intake and poorer motor function was linear. There was no significant association between manganese exposure and hyperactivity. Conclusion: Exposure to manganese in water was associated with poorer neurobehavioral performances in children, even at low levels commonly encountered in North America. Citation: Oulhote Y, Mergler D, Barbeau B, Bellinger DC, Bouffard T, Brodeur ME, Saint-Amour D, Legrand M, Sauvé S, Bouchard MF. 2014. Neurobehavioral function in school-age children exposed to manganese in drinking water. Environ Health Perspect 122:1343–1350; http://dx.doi.org/10.1289/ehp.130791

Motor Learning Improvement Remains 3 Months After a Multisession Anodal tDCS Intervention in an Aging Population

Healthy aging is associated with decline of motor function that can generate serious consequences on the quality of life and safety. Our studies aim to explore the 3-month effects of a 5-day multisession anodal transcranial direct current stimulation (a-tDCS) protocol applied over the primary motor cortex (M1) during motor sequence learning in elderly. The present sham-controlled aging study investigated whether tDCS-induced motor improvements previously observed 1 day after the intervention persist beyond 3 months. A total of 37 cognitively-intact aging participants performed five consecutive daily 20-min sessions of the serial-reaction time task (SRTT) concomitant with either anodal (n = 18) or sham (n = 19) tDCS over M1. All participants performed the Purdue Pegboard Test and transcranial magnetic stimulation (TMS) measures of cortical excitability were collected before, 1 day after and 3 months after the intervention. The last follow-up session also included the execution of the trained SRTT. The main findings are the demonstration of durable effects of a 5-day anodal tDCS intervention at the trained skill, while the active intervention did not differ from the sham intervention at both the untrained task and on measures of M1-disinhibition. Thus, the current article revealed for the first time the durability of functional effects of a-tDCS combined with motor training after only 5 days of intervention in an aging population. This finding provides evidence that the latter treatment alternative is effective in achieving our primary motor rehabilitation goal, that is to allow durable motor training effects in an aging population

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Attention Modulation of Stimulus Rivalry under Swapping Paradigm

Stimulus rivalry refers to the sustained periods of perceptual dominance that occur when different visual stimuli are swapped at a regular rate between eyes. This phenomenon is thought to involve mainly eye-independent mechanisms. Although several studies have reported that attention can increase image predominance in conventional binocular rivalry, it is unknown whether attention can specifically modulate stimulus rivalry. We addressed this question and manipulated the spatial characteristic of the stimuli to assess whether such an attention modulation could depend on visual processing hierarchy. The results showed that selective attention of stimulus rivalry significantly increased the predominance of the attended stimulus, regardless of the stimulus' spatial characteristics. No effect was observed on the swapping percept. The findings are discussed in the context of recent models attempting to characterize stimulus rivalry between eye-dependent and eye-independent levels