Breast Milk Protects Against Gastrointestinal Symptoms in Infants at High Risk for Autism During Early Development.

OBJECTIVES: Parents of children with autism spectrum disorders (ASDs) often report gastrointestinal (GI) dysfunction in their children. The objectives of the present study were to determine whether infants at high risk for developing ASD (ie, siblings of children diagnosed as having ASD) show greater prevalence of GI problems and whether this prevalence is associated with diet and age at weaning from breast milk. METHODS: Using questionnaires, diet history and GI problems were tracked prospectively and retrospectively in 57 high-risk infants and for comparison in 114 low-risk infants (infants from families without ASD history). RESULTS: In low-risk infants, prevalence of GI symptoms, in aggregate, did not vary with diet or age of weaning. By contrast, high-risk infants with GI symptoms were weaned earlier than those without symptoms (P < 0.04), and high-risk infants showed greater prevalence of GI symptoms, in aggregate, on a no breast milk diet than on an exclusive breast milk diet (P < 0.017). Constipation, in particular, was more prevalent in high-risk infants compared with low-risk infants (P = 0.01), especially on a no breast milk diet (P = 0.002). High-risk infants who completed weaning earlier than 6 months showed greater prevalence of constipation (P = 0.001) and abdominal distress (P = 0.004) than those fully weaned after 6 months. CONCLUSIONS: The greater prevalence of GI symptoms in high-risk infants suggests that GI dysfunction during early infant development may be a part of the ASD endophenotype. Late weaning and exclusive breast milk were associated with protection against GI symptoms in high-risk infants.

Effect of digestion and storage of human milk on free fatty acid concentration and cytotoxicity.

OBJECTIVES: Fat is digested in the intestine into free fatty acids (FFAs), which are detergents and therefore toxic to cells at micromolar concentration. The mucosal barrier protects cells in the adult intestine, but this barrier may not be fully developed in premature infants. Lipase-digested infant formula, but not fresh human milk, has elevated FFAs and is cytotoxic to intestinal cells, and therefore could contribute to intestinal injury in necrotizing enterocolitis (NEC), but even infants exclusively fed breast milk may develop NEC. Our objective was to determine whether stored milk and milk from donor milk (DM) banks could also become cytotoxic, especially after digestion. METHODS: We exposed cultured rat intestinal epithelial cells or human neutrophils to DM and milk collected fresh and stored at 4°C or -20°C for up to 12 weeks and then treated for 2 hours (37°C) with 0.1 or 1 mg/mL pancreatic lipase and/or trypsin and chymotrypsin. RESULTS: DM and milk stored 3 days (at 4°C or -20°C) and then digested were cytotoxic. Storage at -20°C for 8 and 12 weeks resulted in an additional increase in cytotoxicity. Protease digestion decreased, but did not eliminate cell death. CONCLUSIONS: Present storage practices may allow milk to become cytotoxic and contribute to intestinal damage in NEC.

The face inversion effect in infants is driven by high, and not low, spatial frequencies.

To investigate the mechanisms underlying development of upright face preferences in infants, the current study measured inversion effects for faces that were spatial frequency (SF) filtered, into low SF and high SF, with the notion that different SFs are analyzed by different visual mechanisms. For comparison to faces, we used object stimuli that consisted of pictures of strollers. In 4 month olds, 8 month olds, and adults, we measured the strength of the selective face inversion effect (sFIE), operationally defined as an upright over inverted looking preference that is greater for faces than objects. In Study 1, we employed unfiltered stimuli, and found a clear sFIE in both infants and adults. To determine what drove this sFIE, in Study 2, the sFIE was measured for low-SF and high-SF stimuli, with all stimuli being equated for visibility. For adults, the sFIE was equally strong for low-SF and high-SF stimuli. A different pattern was seen for infants. Infants exhibited a significantly greater sFIE for high-SF, than for low-SF, stimuli (and only for high SF was the sFIE significant). In fact, the strength of infants' upright face preference for high-SF stimuli was indistinguishable from that observed for unfiltered faces, indicating that in natural (unfiltered) stimuli, high SFs are sufficient to account for infants' upright face preferences.

Development of face discrimination abilities, and relationship to magnocellular pathway development, between childhood and adulthood.

The current study tested the development of face and object processing in young children (mean age = 5.24 years), adolescents (mean age = 15.8 years), and adults (mean age = 21.1 years) using stimuli that were equated for low-level visual characteristics (luminance, contrast, and spatial frequency make-up) and methods that equate for difficulty across ages. We also tested sensitivity to luminance and chromatic contrast (i.e., thought to be mediated primarily by the subcortical Magnocellular (M) and Parvocellular (P) pathways, respectively) to determine whether age-related improvements in face or object discrimination were driven by age-related changes in the M and/or P pathways. Results showed a selective age-related improvement in face sensitivity and a relationship between age-related increases in face sensitivity and luminance contrast sensitivity. These results add to the mounting evidence that the M pathway may influence face processing.

Effects of attention and laterality on motion and orientation discrimination in deaf signers.

Previous studies have asked whether visual sensitivity and attentional processing in deaf signers are enhanced or altered as a result of their different sensory experiences during development, i.e., auditory deprivation and exposure to a visual language. In particular, deaf and hearing signers have been shown to exhibit a right visual field/left hemisphere advantage for motion processing, while hearing nonsigners do not. To examine whether this finding extends to other aspects of visual processing, we compared deaf signers and hearing nonsigners on motion, form, and brightness discrimination tasks. Secondly, to examine whether hemispheric lateralities are affected by attention, we employed a dual-task paradigm to measure form and motion thresholds under "full" vs. "poor" attention conditions. Deaf signers, but not hearing nonsigners, exhibited a right visual field advantage for motion processing. This effect was also seen for form processing and not for the brightness task. Moreover, no group differences were observed in attentional effects, and the motion and form visual field asymmetries were not modulated by attention, suggesting they occur at early levels of sensory processing. In sum, the results show that processing of motion and form, believed to be mediated by dorsal and ventral visual pathways, respectively, are left-hemisphere dominant in deaf signers.

Delayed luminance and chromatic contrast sensitivity in infants with spontaneously regressed retinopathy of prematurity.

BACKGROUND: The current study assessed whether contrast sensitivity is affected in preterm infants with a history of spontaneously regressed retinopathy of prematurity (ROP, Stages 1-3). Specifically, we employed luminance (light/dark) and chromatic (red/green) stimuli, which are mediated by the magnocellular (M) and parvocellular (P) subcortical pathways, respectively. METHODS: Contrast sensitivity (CS) was measured using forced-choice preferential looking testing in 21 infants with a history of ROP and 41 control preterm infants who were born prematurely but did not develop ROP, tested between 8 and 47 weeks (2-11 months) postterm age. Infants were presented with chromatic and luminance drifting sinusoidal gratings, which appeared randomly on the left or right side of the monitor in each trial. The contrast of the stimuli varied across trials and was defined in terms of root mean squared cone contrast for long- and medium-wavelength cones. RESULTS: Between 8 and 25 weeks postterm, ROP infants had significantly worse CS, and there was a trend for greater impairment for luminance than chromatic CS. This delay was not seen at older ages between 26 and 47 weeks postterm. CONCLUSIONS: These findings are consistent with the concept that early maturation of the M pathway is vulnerable to biological insult, as in the case of ROP, to a greater extent than in the P pathway.

Fast development of global motion processing in human infants.

Although global motion processing is thought to emerge early in infancy, there is debate regarding the age at which it matures to an adult-like level. In the current study, we address the possibility that the apparent age-related improvement in global motion processing might be secondary to age-related increases in the sensitivity of mechanisms (i.e., local motion detectors) that provide input to global motion mechanisms. To address this, we measured global motion processing by obtaining motion coherence thresholds using stimuli that were equally detectable in terms of contrast across all individuals and ages (3-, 4-, 5-, 6-, and 7-month-olds and adults). For infants, we employed a directional eye movement (DEM) technique. For adults, we employed both DEM and a self-report method. First, contrast sensitivity was obtained for a local task, using a stochastic motion display in which all the dots moved coherently. Contrast sensitivity increased significantly between 3 and 7 months, and between infancy and adulthood. Each subject was then tested on the global motion task with the contrast of the dots set to 2.5 × each individual's contrast threshold. Coherence thresholds were obtained by varying the percentage of coherently moving "signal" versus "noise" dots in the stochastic motion display. Results revealed remarkably stable global motion sensitivity between 3 and 7 months of age, as well as between infancy and adulthood. These results suggest that the mechanisms underlying global motion processing develop to an adult-like state very quickly.

Digested formula but not digested fresh human milk causes death of intestinal cells in vitro: implications for necrotizing enterocolitis.

BACKGROUND: Premature infants fed formula are more likely to develop necrotizing enterocolitis (NEC) than those who are breastfed, but the mechanisms of intestinal necrosis in NEC and protection by breast milk are unknown. We hypothesized that after lipase digestion, formula, but not fresh breast milk, contains levels of unbound free fatty acids (FFAs) that are cytotoxic to intestinal cells. METHODS: We digested multiple term and preterm infant formulas or human milk with pancreatic lipase, proteases (trypsin and chymotrypsin), lipase + proteases, or luminal fluid from a rat small intestine and tested FFA levels and cytotoxicity in vitro on intestinal epithelial cells, endothelial cells, and neutrophils. RESULTS: Lipase digestion of formula, but not milk, caused significant death of neutrophils (ranging from 47 to 99% with formulas vs. 6% with milk) with similar results in endothelial and epithelial cells. FFAs were significantly elevated in digested formula vs. milk and death from formula was significantly decreased with lipase inhibitor pretreatment, or treatments to bind FFAs. Protease digestion significantly increased FFA binding capacity of formula and milk but only enough to decrease cytotoxicity from milk. CONCLUSION: FFA-induced cytotoxicity may contribute to the pathogenesis of NEC.

Synaesthetic associations decrease during infancy.

Early development is characterized by a period of exuberant neural connectivity followed by a retraction and reweighting of connections over the course of development. It has been proposed that this connectivity may facilitate arbitrary sensory experiences in infants that are unlike anything experienced by typical adults but are similar to the sensory experiences of adults with synaesthesia, a rare sensory phenomenon that has been associated with exuberant neural connectivity and that is characterized by strong arbitrary associations between different sensations. We provide the first evidence for this infant-synaesthesia hypothesis by showing that the presence of particular shapes influences color preferences in typical 2- and 3-month-olds, but not in 8-month-olds or adults. These results are consistent with the possibility that exuberant neural connectivity facilitates synaesthetic associations during infancy that are typically eliminated during development, but that a failure of the retraction process leads in rare cases to synaesthesia in adults.

Diminished parietal cortex activity associated with poor motion direction discrimination performance in schizophrenia.

The results of multiple investigations indicate visual motion-processing abnormalities in schizophrenia. There is little information, however, about the time course and neural correlates of motion-processing abnormalities among these subjects. For the present study, 13 schizophrenia and 13 healthy subjects performed a simple motion direction discrimination task with peripherally presented moving grating stimuli (5 or 10 deg/s). Dense-array electroencephalography data were collected simultaneously. The goal was to discern whether neural deviations associated with motion-processing abnormalities among schizophrenia patients occur early or late in the visual-processing stream. Schizophrenia patients were worse at judging the direction of motion gratings, had enhanced early neural activity (about 90 ms after stimulus onset), and deficient target detection-related late neural activity over parietal cortex (about 400 ms after stimulus onset). In addition, there was a strong association (accounting for 36% of performance variance) between poor behavioral performance and lower target detection-related brain activity among schizophrenia patients. These findings suggest that abnormalities in later stages of motion-processing mechanisms, perhaps beyond extrastriate cortex, may account for behavioral deviations among schizophrenia subjects.

Does visual modularity increase over the course of development?

Early in postnatal development, the brain produces exuberant connections, some of which are later retracted, a process that is thought to play a role in the formation of functionally segregated modules in the brain. In the case of visual development, retraction between visual areas might underlie the known psychophysical and neural segregation of processing for different aspects of vision (e.g., color, motion, form, depth) known to exist in adults. This review covers the psychophysical evidence for increasing dissociation between visual modules over the course of development, and provides insight into the possible functions of this developmental alteration.

Chromatic and luminance contrast sensitivity in fullterm and preterm infants.

In order to investigate the contributions of visual experience vs. preprogrammed mechanisms on visual development, the current study compared contrast sensitivity in preterm vs. fullterm infants. If development is tied to time since conception, preterm infants should match the developmental trajectories of fullterm infants when plotted in postterm age. By contrast, if development is influenced by visual experience, preterm and fullterm infants should match when plotted in postnatal age. Luminance (light/dark) and chromatic (red/green) contrast sensitivities (CS) were measured in 25 preterm (born, on average, 6.6 weeks early) and 77 fullterm infants, between 1 and 6 months postterm. In the first few months, luminance CS was found to be predicted by postterm age, suggesting that preprogrammed development is sufficient to account for luminance CS. By contrast, chromatic CS exceeded that predicted by postterm age, which suggests that time since birth confers a benefit on chromatic CS. The preterms' 6.6 weeks of additional time since birth is roughly equivalent to 3.7 weeks of development in chromatic CS. In sum, these results suggest that chromatic CS is more influenced by early postnatal visual experience than luminance CS, which may have implications for development of parvocellular and magnocellular pathways.

Effects of gestational length, gender, postnatal age, and birth order on visual contrast sensitivity in infants.

To investigate effects of visual experience versus preprogrammed mechanisms on visual development, we used multiple regression analysis to determine the extent to which a variety of variables (that differ in the extent to which they are tied to visual experience) predict luminance and chromatic (red/green) contrast sensitivity (CS), which are mediated by the magnocellular (M) and parvocellular (P) subcortical pathways, respectively. Our variables included gestational length (GL), birth weight (BW), gender, postnatal age (PNA), and birth order (BO). Two-month-olds (n = 60) and 6-month-olds (n = 122) were tested. Results revealed that (1) at 2 months, infants with longer GL have higher luminance CS; (2) at both ages, CS significantly increases over a approximately 21-day range of PNA, but this effect is stronger in 2- than 6-month-olds and stronger for chromatic than luminance CS; (3) at 2 months, boys have higher luminance CS than girls; and (4) at 2 months, firstborn infants have higher CS, while at 6 months, non-firstborn infants have higher CS. The results for PNA/GL are consistent with the possibility that P pathway development is more influenced by variables tied to visual experience (PNA), while M pathway development is more influenced by variables unrelated to visual experience (GL). Other variables, including prenatal environment, are also discussed.

Analysis of the visual spatiotemporal properties of American Sign Language.

Careful measurements of the temporal dynamics of speech have provided important insights into phonetic properties of spoken languages, which are important for understanding auditory perception. By contrast, analytic quantification of the visual properties of signed languages is still largely uncharted. Exposure to sign language is a unique experience that could shape and modify low-level visual processing for those who use it regularly (i.e., what we refer to as the Enhanced Exposure Hypothesis). The purpose of the current study was to characterize the visual spatiotemporal properties of American Sign Language (ASL) so that future studies can test the enhanced exposure hypothesis in signers, with the prediction that altered vision should be observed within, more so than outside, the range of properties found in ASL. Using an ultrasonic motion tracking system, we recorded the hand position in 3-dimensional space over time during sign language production of signs, sentences, and narratives. From these data, we calculated several metrics: hand position and eccentricity in space and hand motion speed. For individual signs, we also measured total distance travelled by the dominant hand and total duration of each sign. These metrics were found to fall within a selective range, suggesting that exposure to signs is a specific and unique visual experience, which might alter visual perceptual abilities in signers for visual information within the experienced range, even for non-language stimuli.

Abnormal magnocellular pathway visual processing in infants at risk for autism.

BACKGROUND: A wealth of data has documented impairments in face processing in individuals with autism spectrum disorders (ASD). Recently, the suggestion has been made that these impairments may arise from abnormal development of a subcortical system involved in face processing that originates in the magnocellular pathway of the primate visual system. METHODS: To test this developmental hypothesis, we obtained visual perceptual data from 6-month-old infants who were at risk for ASD because they had an older sibling diagnosed with the disorder ("high-risk infants"). To measure sensitivity of the magnocellular (M) pathway and, for comparison, of the parvocellular (P) visual pathway, we employed visual stimuli designed to selectively stimulate the two. Sensitivity data from high-risk infants (n = 13) were compared with data from matched control infants (i.e., "low-risk" infants with no family history of ASD, n = 26). RESULTS: On the P pathway stimulus, high-risk infants exhibited sensitivities that were identical to those of control infants. By contrast, on the M pathway stimulus, high-risk infants exhibited sensitivities nearly twofold greater than those of control infants. CONCLUSIONS: Given that ASD and its symptoms are known to run in families, these preliminary results suggest that ASD may be associated with abnormal M pathway function early in infancy, which may aid in early diagnosis of the disorder.

Compromised speed discrimination among schizophrenia patients when viewing smooth pursuit targets.

Schizophrenia subjects' smooth pursuit abnormalities may reflect a problem with perception of motion, although evidence comes primarily from reports using stimuli that differ from standard smooth pursuit stimuli (i.e. moving gratings or coherent dots). This study presented schizophrenia and healthy subjects with a forced-choice speed discrimination paradigm using smooth pursuit-like stimuli. The schizophrenia subject's motion processing was impaired, as evidenced by their significantly higher speed discrimination thresholds (a difference that was 1.7 larger for the patient group). Abnormalities of motion perception in schizophrenia, even for simple stimuli, suggest a problem with motion processing in area MT.

Effects of spatial attention and salience cues on chromatic and achromatic motion processing.

While several previous psychophysical and neurophysiological studies have demonstrated chromatic (red/green) input to motion processing, the nature of this input is still a matter of debate. In particular, there exists controversy as to whether chromatic motion processing is mediated by low-level motion mechanisms versus higher-level, attention- or salience-based mechanisms. To address the role of attention, in Experiment 1, we asked whether spatial attention exerts larger effects on chromatic (red/green), as compared to achromatic, motion. To this end, we employed a motion after-effect (MAE) paradigm, and measured attention effects by comparing MAE duration between conditions where subjects attended to the adapting moving grating stimulus versus ignored that stimulus because they were required to perform an attentionally demanding vowel detection task at the center of gaze. The results from these experiments revealed equal effects of spatial attention on chromatic and achromatic motion processing, which were essentially constant (roughly 1.4-fold) across a wide range of stimulus contrasts (3.2-25% cone contrast). These findings suggest that chromatic motion processing is not affected disproportionally by higher-level spatial attention mechanisms. To address the role of salience, in Experiment 2, we investigated the effects of bottom-up salience cues on the strength of chromatic and achromatic motion, as measured with the MAE. Salience was manipulated by varying the relationship between the moving gratings and the background color. The results of these experiments revealed small and insignificant effects of salience cues on chromatic and achromatic motion processing. These findings suggest that mechanisms sensitive to feature salience do not influence low-level chromatic motion mechanisms mediating the motion after-effect.

Increased Prevalence of Unusual Sensory Behaviors in Infants at Risk for, and Teens with, Autism Spectrum Disorder.

The current study investigated the prevalence and pattern of unusual sensory behaviors (USBs) in teens with Autism Spectrum Disorder (ASD) and infants (3-36 months) at risk for ASD. From two different sites (UCSD and UConn), caregivers of infants at high (n = 32) and low risk (n = 33) for ASD, and teenagers with (n = 12) and without ASD (n = 11), completed age-appropriate Sensory Profile questionnaires (Infant/Toddler Sensory Profile; Dunn 2002; Adolescent/Adult Sensory Profile; Brown and Dunn 2002). The results show that high-risk infants and teenagers with ASD exhibit higher-than-typical prevalence of USBs. Results of our distribution analyses investigating the direction of sensory atypicalities (greater-than-typical vs. less-than-typical) revealed a fair degree of consistency amongst teens, however, USB patterns were more varied in high-risk infants.

Integration of one- and two-dimensional motion signals in infants: evidence from the barber-pole illusion.

Several previous studies in adults have investigated how one- and two-dimensional moving features are integrated into a coherent global motion percept by studying the "barber-pole illusion"; when a one-dimensional moving grating is presented within a rectangular aperture, the two-dimensional line terminators at the edges of the aperture bias the perceived direction of motion toward the longer axis of the aperture. In the current study, we used barber-pole stimuli to investigate the development of motion mechanisms that integrate one- and two-dimensional motion signals. Using a directional eye movement technique, we measured responses to obliquely moving gratings presented within horizontally vs. vertically oriented apertures, in infants (ages 2-5 months) and adults. For all ages, we found that horizontal eye movements were significantly stronger when gratings were presented within horizontal than within vertical apertures, as predicted by the barber-pole illusion. Additionally, we devised a way to infer the "effective shift" in eye movement direction produced by the barber-pole illusion. Using a simple motion integration model, effective shift values were then used to calculate the relative weightings of one- and two-dimensional motion signals to direction coding. The results show that by 2 months of age, infants integrate one- and two-dimensional motion signals, and that the relative weighting of one- and two-dimensional signals remains roughly constant from 2 months of age into adulthood.

Attentional effects on contrast discrimination in humans: evidence for both contrast gain and response gain.

In order to understand how attention affects visual processing, we investigated the degree to which attention effects can be accounted for by increases in the contrast gain of the contrast response function, CRF (represented by an increase in effective contrast) vs. increases in the response gain (represented by an overall amplification of response). To this end, we used a dual-task paradigm to compare psychophysical "threshold vs. pedestal contrast" (TvC) curves obtained under conditions of full- vs. poor-attention. The attention effect, defined as the ratio of thresholds for poor- vs. full-attention conditions, was roughly four-fold at a pedestal contrast of 0% (i.e., at detection threshold) and there was a significant decrease in attention effect with increasing pedestal contrast, from approximately ten-fold at the lowest non-zero pedestal contrast tested (0.25%) to three-fold at the highest pedestal contrast tested (64%). These findings are consistent with the existence of both contrast gain effects of attention (needed to account for the substantial attention effect at detection threshold and the decrease in attention effect with increasing pedestal contrast) as well as response gain effects of attention (needed to account for the fact that attention was beneficial across all pedestal contrasts-rather than harmful at some contrasts, as a pure contrast gain model would predict). The results of a model fitting Naka-Rushton CRF equations to the TvC data also support this conclusion. Here we found a two-fold increase in contrast gain and a five-fold increase in response gain in the CRF for the full-attention, as compared to the poor-attention, condition. Because pure contrast gain effects, on the order of two-fold, have been observed at early stages of visual processing (for example in areas V4 and MT), our psychophysical results suggest a hybrid model of attention; contrast gain control at an early stage of visual processing, followed by response gain control at a later stage.