ω-3 and ω-6 Fatty Acid Supplementation May Reduce Autism Symptoms Based on Parent Report in Preterm Toddlers.

Background: Children born preterm are at increased risk of autism spectrum disorder (ASD). n-3 (ω-3) Combined with n-6 (ω-6) fatty acids including γ-linolenic acid (GLA) may benefit children born preterm showing early signs of ASD. Previous trials have reported that docosahexaenoic acid (DHA) promotes cognitive development in preterm neonates and n-3 fatty acids combined with GLA improve attention-deficit-hyperactivity disorder. Objectives: The objectives of the pilot Preemie Tots Trial were 1) to confirm the feasibility of a full-scale trial in toddlers born very preterm and exhibiting ASD symptoms and 2) to explore the effects of supplementation on parent-reported ASD symptoms and related behaviors. Methods: This was a 90-d randomized, fully blinded, placebo-controlled trial in 31 children 18-38 mo of age who were born at ≤29 wk of gestation. One group was assigned to daily Omega-3-6-9 Junior (Nordic Naturals, Inc.) treatment (including 338 mg eicosapentaenoic acid, 225 mg DHA, and 83 mg GLA), and the other group received canola oil (124 mg palmitic acid, 39 mg stearic acid, 513 mg linoleic acid, 225 mg α-linolenic acid, and 1346 mg oleic acid). Mixed-effects regression analyses followed intent-to-treat analysis and explored effects on parent-reported ASD symptoms and related behaviors. Results: Of 31 children randomly assigned, 28 had complete outcome data. After accounting for baseline scores, those assigned to treatment exhibited a greater reduction in ASD symptoms per the Brief Infant Toddler Social Emotional Assessment ASD scale than did those assigned to placebo (difference in change = - 2.1 points; 95% CI: - 4.1, - 0.2 points; standardized effect size = - 0.71). No other outcome measure reflected a similar magnitude or a significant effect. Conclusions: This pilot trial confirmed adequate numbers of children enrolled and participated fully in the trial. No safety concerns were noted. It also found clinically-significant improvements in ASD symptoms for children randomly assigned to receive Omega-3-6-9 Junior, but effects were confined to one subscale. A future full-scale trial is warranted given the lack of effective treatments for this population. This trial was registered at www.clinicaltrials.gov as NCT01683565.

Learning to recognize letters in the periphery: Effects of repeated exposure, letter frequency, and letter complexity.

Patients with central vision loss must rely on their peripheral vision for reading. Unfortunately, limitations of peripheral vision, such as crowding, pose significant challenges to letter recognition. As a result, there is a need for developing effective training methods for improving crowded letter recognition in the periphery. Several studies have shown that extensive practice with letter stimuli is beneficial to peripheral letter recognition. Here, we explore stimulus-related factors that might influence the effectiveness of peripheral letter recognition training. Specifically, we examined letter exposure (number of letter occurrences), frequency of letter use in English print, and letter complexity and evaluated their contributions to the amount of improvement observed in crowded letter recognition following training. We analyzed data collected across a range of training protocols. Using linear regression, we identified the best-fitting model and observed that all three stimulus-related factors contributed to improvement in peripheral letter recognition with letter exposure being the most important factor. As an important explanatory variable, pretest accuracy was included in the model as well to avoid estimate biases and was shown to have influence on the relationship between training improvement and letter exposure. When developing training protocols for peripheral letter recognition, it may be beneficial to not only consider the overall length of training, but also to tailor the number of stimulus occurrences for each letter according to its initial performance level, frequency, and complexity.

Breastfeeding and dietary variety among preterm children aged 1-3 years.

Among infants born at term, breastfeeding is associated with increased dietary variety in childhood. Preterm birth can limit early feeding options while simultaneously increasing risk for negative health outcomes that could benefit from dietary-based preventative measures. We assessed whether breastfeeding is associated with increased dietary variety at 1-3 years amongst children born preterm. We analyzed baseline data from two clinical trials investigating cognitive development after fatty-acid supplementation for 10-39 month-old children born before 35 weeks gestation (n = 189). At baseline, mothers reported breastfeeding history and completed a 161-item food-frequency questionnaire for their child. Dietary variety was assessed via 3 measures: (1) proportion items consumed at least once per month, (2) servings of a given item consumed relative to total monthly food servings, (3) daily probability of consuming a given item. Overall, 88% of children were ever breastfed (median duration = 89 days, range = 0-539), and 48% of children were ever exclusively breastfed (median duration = 59 days, range = 3-240). Exclusive breastfeeding duration was associated with dietary variety increases of 0.9% (95% CI = 0.1-1.7) for vegetables, 1.6% (95% CI = 0.2-3.0) for meat/fish, and 1.3% (95% CI = 0.2-2.4) for grain/starch, for each additional month of exclusive breastfeeding after adjustment for key confounders. Correspondingly, the variety of sweets consumed decreased by 1.2% (CI: -2.1, -0.3) per month of any breastfeeding after adjustment. These results are consistent with those in children born at term, and if causal, could provide additional support for exclusive breastfeeding to improve diet and health in children born preterm.

Breastfeeding and Autism Spectrum Disorder in the National Survey of Children's Health.

BACKGROUND: Breastfeeding is thought to promote healthy cognitive development. A small number of studies have also reported a protective association between breastfeeding and autism spectrum disorder (ASD). The National Survey of Children's Health (2007, 2011), a large nationally representative survey of US children, was examined to determine whether breastfeeding of infants is associated with later development of ASD. METHODS: Respondents with a child ages 2-5 years (n = 37,901) were queried about whether their child was currently diagnosed with ASD and about their child's breastfeeding history. Additional information was available about child and family health history and family demographics. Survey-weighted logistic regressions were employed to examine ASD diagnosis as associated with several breastfeeding exposure metrics including a history of partial or exclusive breastfeeding for the first 3 or 6 months, and duration of partial or exclusive breastfeeding. RESULTS: Across models, a current diagnosis of ASD (n = 391) was unassociated with any measure of breastfeeding history. Adjusted odds ratios for categorical breastfeeding exposures ranged from 0.68 (confidence interval [CI] = 0.4, 1.3) for any partial breastfeeding to 0.74 (CI = 0.3, 1.7) for 6 months of exclusive breastfeeding. When exposure was measured continuously, adjusted odds ratios were 1.03 (CI = 0.97, 1.10) for each additional month of partial breastfeeding and 1.04 (CI = 0.96, 1.13) for each additional month of exclusive breastfeeding. CONCLUSION: These findings call into question the results from the small body of research that has examined this issue to date.

The efficiency of second order orientation coherence detection.

Neurons in early visual cortex respond to both luminance- (1st order) and contrast-modulated (2nd order) local features in the visual field. In later extra-striate areas neurons with larger receptive fields integrate information across the visual field. For example, local luminance-defined features can be integrated into contours and shapes. Evidence for the global integration of features defined by contrast-modulation is less well established. While good performance in some shape tasks has been demonstrated with 2nd order stimuli, the integration of contours fails with 2nd order elements. Recently we developed a global orientation coherence task that is more basic than contour integration, bearing similarity to the well-established global motion coherence task. Similar to our previous 1st order result for this task, we find 2nd order coherence detection to be scale-invariant. There was a small but significant threshold elevation for 2nd order relative to 1st order. We used a noise masking approach to compare the efficiency of orientation integration for the 1st and 2nd order. We find a significant deficit for 2nd order detection at both the local and global level, however the small size of this effect stands in stark contrast against previous results from contour-integration experiments, which are almost impossible with 2nd order stimuli.

The effect of motion on crowding: zooming text.

Crowding is the major sensory factor responsible for the slow reading speeds exhibited in peripheral vision. Past attempts to improve peripheral reading via crowding reduction have generally focused on applying spatial changes to the stimulus and have been largely ineffective. Recent evidence indicates that dynamic approaches have good potential for reducing crowding in peripheral reading. We tested this hypothesis by introducing "zooming" motion (smooth letter resizing across the presentation duration) to trigram stimuli (groups of three randomly selected letters) presented at 10° in the lower visual field and evaluating recognition of the middle letter. Crowding was alleviated in the presence of this motion, both when dynamic cues were introduced to all letters in the trigram simultaneously and when they were applied to individual letters alone. The magnitude and direction of crowding reduction depended on the amplitude and direction of motion. These results suggest that dynamic presentation may be a useful tool for improving peripheral reading through reducing letter crowding. Zooming motion, in particular, has the additional advantage of conserving text layout, making it a good candidate for such an application.

A two-stage model of orientation integration for Battenberg-modulated micropatterns.

The visual system pools information from local samples to calculate textural properties. We used a novel stimulus to investigate how signals are combined to improve estimates of global orientation. Stimuli were 29 × 29 element arrays of 4 c/deg log Gabors, spaced 1° apart. A proportion of these elements had a coherent orientation (horizontal/vertical) with the remainder assigned random orientations. The observer's task was to identify the global orientation. The spatial configuration of the signal was modulated by a checkerboard pattern of square checks containing potential signal elements. The other locations contained either randomly oriented elements ("noise check") or were blank ("blank check"). The distribution of signal elements was manipulated by varying the size and location of the checks within a fixed-diameter stimulus. An ideal detector would only pool responses from potential signal elements. Humans did this for medium check sizes and for large check sizes when a signal was presented in the fovea. For small check sizes, however, the pooling occurred indiscriminately over relevant and irrelevant locations. For these check sizes, thresholds for the noise check and blank check conditions were similar, suggesting that the limiting noise is not induced by the response to the noise elements. The results are described by a model that filters the stimulus at the potential target orientations and then combines the signals over space in two stages. The first is a mandatory integration of local signals over a fixed area, limited by internal noise at each location. The second is a task-dependent combination of the outputs from the first stage.

Global processing of orientation in amblyopia.

We set out to determine whether extra-striate ventral stream function was compromised in amblyopia and to compare any observed deficit with previous data on comparable dorsal stream function. We devised a multi-element orientation task where orientation coherence sensitivity could be measured in a comparable way to motion coherence. The use of spatial frequency narrowband elements allowed for accurate correction of any upstream contrast sensitivity influence and ensured that the orientation bandwidth of our elements did not covary with the measured coherence. Using a standard equivalent noise analysis, we varied both the local orientation bandwidth of individual elements as well as the global orientation bandwidth of the element array to obtain estimates of both local and global internal noise and efficiency. The results show that for this ventral stream task there is only a subtle amblyopic deficit in processing global orientation relative to control observers. This deficit is present for both amblyopic and fixing eyes, and appears to reflect poorer efficiency in processing local orientation, suggesting a subtle deficit at the input stage to extra-striate cortex where orientation coherence is processed.

Orientation coherence sensitivity.

We developed a global orientation coherence task for the assessment of global form processing along similar lines to the global motion coherence task. The task involved judgments of global orientation for an array of limited duration 1-D Gabors, some of which were signal (signal orientation) and some of which were noise (random orientation). We address two issues. First: Do motion and form global processing have similar dependencies? And second: Can global sensitivity be explained solely in terms of integrative function? While most dependencies (e.g., contrast, spatial scale, and field size) are similar for form and motion processing, there is a greater dependence on eccentricity for form processing. Sensitivity for global tasks involves more than just integration by filters broadly tuned for orientation. Results are best modeled by filters with narrowband orientation tuning that effectively segregate as well as integrate global information.

Amblyopic deficits in processing structure-from-motion.

Amblyopic observers exhibit a range of low- and high-level cortical deficits, and there is strong evidence that the extrastriate cortex is selectively affected for signal/noise tasks but not for simple integration tasks. We tested amblyopic and control observers on a structure-from-motion (SFM) task involving signal integration to gauge whether extrastriate processing is compromised at a level where dorsal and ventral information is combined. SFM tasks require integration of local elements to perceive the global structure using motion-defined depth cues. Observers were monocularly presented with a 2-IFC shape discrimination task and asked to indicate whether two consecutive SFM stimuli represented the same or different depth-defined shapes. Amblyopic observers had higher depth thresholds than control observers, even after controlling for low-level differences in contrast thresholds across eyes and observers. Combined with the presence of the deficit in both the amblyopic and fellow-fixing eyes, this suggests a high-level locus for the SFM deficit.

Healthy aging delays scalp EEG sensitivity to noise in a face discrimination task.

We used a single-trial ERP approach to quantify age-related changes in the time-course of noise sensitivity. A total of 62 healthy adults, aged between 19 and 98, performed a non-speeded discrimination task between two faces. Stimulus information was controlled by parametrically manipulating the phase spectrum of these faces. Behavioral 75% correct thresholds increased with age. This result may be explained by lower signal-to-noise ratios in older brains. ERP from each subject were entered into a single-trial general linear regression model to identify variations in neural activity statistically associated with changes in image structure. The fit of the model, indexed by R(2), was computed at multiple post-stimulus time points. The time-course of the R(2) function showed significantly delayed noise sensitivity in older observers. This age effect is reliable, as demonstrated by test-retest in 24 subjects, and started about 120 ms after stimulus onset. Our analyses suggest also a qualitative change from a young to an older pattern of brain activity at around 47 ± 4 years old.

Age-related delay in information accrual for faces: evidence from a parametric, single-trial EEG approach.

BACKGROUND: In this study, we quantified age-related changes in the time-course of face processing by means of an innovative single-trial ERP approach. Unlike analyses used in previous studies, our approach does not rely on peak measurements and can provide a more sensitive measure of processing delays. Young and old adults (mean ages 22 and 70 years) performed a non-speeded discrimination task between two faces. The phase spectrum of these faces was manipulated parametrically to create pictures that ranged between pure noise (0% phase information) and the undistorted signal (100% phase information), with five intermediate steps. RESULTS: Behavioural 75% correct thresholds were on average lower, and maximum accuracy was higher, in younger than older observers. ERPs from each subject were entered into a single-trial general linear regression model to identify variations in neural activity statistically associated with changes in image structure. The earliest age-related ERP differences occurred in the time window of the N170. Older observers had a significantly stronger N170 in response to noise, but this age difference decreased with increasing phase information. Overall, manipulating image phase information had a greater effect on ERPs from younger observers, which was quantified using a hierarchical modelling approach. Importantly, visual activity was modulated by the same stimulus parameters in younger and older subjects. The fit of the model, indexed by R2, was computed at multiple post-stimulus time points. The time-course of the R2 function showed a significantly slower processing in older observers starting around 120 ms after stimulus onset. This age-related delay increased over time to reach a maximum around 190 ms, at which latency younger observers had around 50 ms time lead over older observers. CONCLUSION: Using a component-free ERP analysis that provides a precise timing of the visual system sensitivity to image structure, the current study demonstrates that older observers accumulate face information more slowly than younger subjects. Additionally, the N170 appears to be less face-sensitive in older observers.

Time course and robustness of ERP object and face differences.

Conflicting results have been reported about the earliest "true" ERP differences related to face processing, with the bulk of the literature focusing on the signal in the first 200 ms after stimulus onset. Part of the discrepancy might be explained by uncontrolled low-level differences between images used to assess the timing of face processing. In the present experiment, we used a set of faces, houses, and noise textures with identical amplitude spectra to equate energy in each spatial frequency band. The timing of face processing was evaluated using face-house and face-noise contrasts, as well as upright-inverted stimulus contrasts. ERP differences were evaluated systematically at all electrodes, across subjects, and in each subject individually, using trimmed means and bootstrap tests. Different strategies were employed to assess the robustness of ERP differential activities in individual subjects and group comparisons. We report results showing that the most conspicuous and reliable effects were systematically observed in the N170 latency range, starting at about 130-150 ms after stimulus onset.

Inverting houses and textures: investigating the characteristics of learned inversion effects.

Faces, more than other objects, are identified more accurately when upright than inverted. This inversion effect may be linked to differences in expertise. Here, we explore how stimulus characteristics and expertise interact to determine the magnitude of inversion effects. Observers were trained to identify houses or textures. Inversion effects were not found with either stimulus before training, but were found following 5 days of practice. Additionally, the learning-induced inversion effects showed partial transfer to novel exemplars. Although similar amounts of learning were observed with both types of stimuli, inversion effects were significantly larger for textures. Our results suggest that the size of the inversion effect is not a reliable index of face-specific processing.

Single-trial EEG dynamics of object and face visual processing.

There has been extensive work using early event-related potentials (ERPs) to study visual object processing. ERP analyses focus traditionally on mean amplitude differences, with the implicit assumption that all of the neuronal activity of interest is evoked by the stimulus in a time-locked manner from trial to trial. However, several recent studies have suggested that visual ERP components might be explained to a large extent by the partial phase resetting of ongoing activity in restricted frequency bands. Here we apply that approach to the neural processing of visual objects. We examine the single-trial dynamics of the EEG signal elicited by the presentation of noise textures, houses and faces. We show that the brain response to those stimuli is best explained by amplitude increase that is maximal in the 5- to 15-Hz frequency band. The results indicate also the presence of a substantial increase in phase coherence in the same frequency band. However, analyses of residual activity, after subtracting the mean from single trials, show that this increase in phase coherence is not due to phase resetting per se, but rather to the presence of the ERP+noise in each trial. In keeping with this idea, a simulation demonstrates that a purely evoked model of the ERP produces quantitatively very similar results. Finally, the stronger response to faces compared to other objects (the 'N170 face effect') can be explained by a pure modulation of amplitude centered in the 5- to 15-Hz band.

Spatial scaling factors explain eccentricity effects on face ERPs.

Event-related potential (ERP) studies consistently have described a strong, face-sensitive response termed the N170. This component is maximal at the fovea and decreases strongly with eccentricity, a result that could suggest a foveal bias in the cortical generators responsible for face processing. Here we demonstrate that scaling stimulus size according to V1 cortical magnification factor can virtually eliminate face-related eccentricity effects, indicating that eccentricity effects on face ERPs are largely due to low-level visual factors rather than high-level cortical specialization for foveal stimuli.