Atypical hemispheric specialization for faces in infants at risk for autism spectrum disorder

Among the many experimental findings that tend to distinguish those with and without autism spectrum disorder (ASD) are face processing deficits, reduced hemispheric specialization, and atypical neurostructural and functional connectivity. To investigate the earliest manifestations of these features, we examined lateralization of event-related gamma-band coherence to faces during the first year of life in infants at high risk for autism (HRA; defined as having an older sibling with ASD) who were compared with low-risk comparison (LRC) infants, defined as having no family history of ASD. Participants included 49 HRA and 46 LRC infants who contributed a total of 127 data sets at 6 and 12 months. Electroencephalography was recorded while infants viewed images of familiar/unfamiliar faces. Event-related gamma-band (30-50 Hz) phase coherence between anterior-posterior electrode pairs for left and right hemispheres was computed. Developmental trajectories for lateralization of intra-hemispheric coherence were significantly different in HRA and LRC infants: by 12 months, HRA infants showed significantly greater leftward lateralization compared with LRC infants who showed rightward lateralization. Preliminary results indicate that infants who later met criteria for ASD were those that showed the greatest leftward lateralization. HRA infants demonstrate an aberrant pattern of leftward lateralization of intra-hemispheric coherence by the end of the first year of life, suggesting that the network specialized for face processing may develop atypically. Further, infants with the greatest leftward asymmetry at 12 months where those that later met criteria for ASD, providing support to the growing body of evidence that atypical hemispheric specialization may be an early neurobiological marker for ASD.R01 DC010290 - NIDCD NIH HHS; R01-DC010290 - NIDCD NIH HH

Developmental Trajectories of Resting EEG Power: An Endophenotype of Autism Spectrum Disorder

Current research suggests that autism spectrum disorder (ASD) is characterized by asynchronous neural oscillations. However, it is unclear whether changes in neural oscillations represent an index of the disorder or are shared more broadly among both affected and unaffected family members. Additionally, it remains unclear how early these differences emerge in development and whether they remain constant or change over time. In this study we examined developmental trajectories in spectral power in infants at high- or low-risk for ASD. Spectral power was extracted from resting EEG recorded over frontal regions of the scalp when infants were 6, 9, 12, 18 and 24 months of age. We used multilevel modeling to assess change over time between risk groups in the delta, theta, low alpha, high alpha, beta, and gamma frequency bands. The results indicated that across all bands, spectral power was lower in high-risk infants as compared to low-risk infants at 6-months of age. Furthermore high-risk infants showed different trajectories of change in spectral power in the subsequent developmental window indicating that not only are the patterns of change different, but that group differences are dynamic within the first two years of life. These findings remained the same after removing data from a subset of participants who displayed ASD related behaviors at 24 or 36 months. These differences in the nature of the trajectories of EEG power represent important endophenotypes of ASD

Personal Familiarity Influences the Processing of Upright and Inverted Faces in Infants

Infant face processing becomes more selective during the first year of life as a function of varying experience with distinct face categories defined by species, race, and age. Given that any individual face belongs to many such categories (e.g. A young Caucasian man's face) we asked how the neural selectivity for one aspect of facial appearance was affected by category membership along another dimension of variability. 6-month-old infants were shown upright and inverted pictures of either their own mother or a stranger while event-related potentials (ERPs) were recorded. We found that the amplitude of the P400 (a face-sensitive ERP component) was only sensitive to the orientation of the mother's face, suggesting that “tuning” of the neural response to faces is realized jointly across multiple dimensions of face appearance

Dental complications in homocystinurias

Background: Cystathionine beta synthase deficiency (causing classical homocystinuria) has been associated with high-arched palates and crowded teeth, but little has been said about other oral health complications. Other homocystinurias (e.g., the remethylation defects) also have had little reported in terms of oral health. Individuals with the homocystinurias have been described as having bone density issues which can correlate with oral health. Moreover, elevations in homocysteine have a theoretical impact on tooth health and the paucity of clinical reports of oral health issues in homocystinuria may be the consequence of lack of attention by the medical community. Significance: Oral health is essential to overall health. If inadequate attention is paid to the oral health complications which can be seen in homocystinurias, then appropriate referrals and attention in therapeutic guidelines will not reflect the importance of oral health. Specific aims/research question: What oral health complications are reported by individuals with homocystinurias? Do these differ according to diagnosis? Methods: Data were collected from patients with homocystinurias by a series of questionnaires using the RARE-X platform. All subjects were consented prior to the collection of their data. All research was performed in accordance with the Declaration of Helsinki. Demographic data were collected as the initial questionnaire and other data were collected via the oral health questionnaire. Analysis: Questionnaires were opened to the community in mid-2022 and collection of data for this study ended with data submitted up to November 2022. Descriptive statistics were done. Due to the small size of the cohort, additional statistical analyses were not attempted. Results: Patients with homocystinuria, not related to cystathionine beta synthase deficiency, are reporting some tooth structure differences. The cohort taken as a whole does not have increased risk for gingivitis, but there appears to be a risk for long-term gum disease possibly due to the rate of osteoporosis/osteopenia in this population. A large number of individuals have malalignment and malocclusion of the teeth. These data highlight oral health as an important component of care in individuals with the homocystinurias as is true of the general population at large

Resting and task-modulated high-frequency brain rhythms measured by scalp encephalography in infants with tuberous sclerosis complex.

The electrophysiological correlates of cognitive deficits in tuberous sclerosis complex (TSC) are not well understood, and modulations of neural dynamics by neuroanatomical abnormalities that characterize the disorder remain elusive. Neural oscillations (rhythms) are a fundamental aspect of brain function, and have dominant frequencies in a wide frequency range. The spatio-temporal dynamics of these frequencies in TSC are currently unknown. Using a novel signal decomposition approach this study investigated dominant cortical frequencies in 10 infants with TSC, in the age range 18-30 months, and 12 age-matched healthy controls. Distinct spectral characteristics were estimated in the two groups. High-frequency [in the high-gamma (>50 Hz) and ripple (>80 Hz) ranges], non-random EEG components were identified in both TSC and healthy infants at 18 months. Additional components in the lower gamma (30-50 Hz) ranges were also identified, with higher characteristic frequencies in TSC than in controls. Lower frequencies were statistically identical in both sub-groups. A significant shift in the high-frequency spectral content of the EEG was observed as a function of age, independently of task performance, possibly reflecting an overall maturation of developing neural circuits. This shift occurred earlier in healthy infants than in TSC, i.e., by age 20 months the highest dominant frequencies were in the high gamma range, whereas in TSC dominant frequencies above 100 Hz were still measurable. At age 28-30 months a statistically significant decrease in dominant high frequencies was observed in both TSC and healthy infants, possibly reflecting increased myelination and neuronal connection strengthening with age. Although based on small samples, and thus preliminary, the findings in this study suggest that dominant cortical rhythms, a fundamental aspect of neurodynamics, may be affected in TSC, possibly leading to impaired information processing in the brain

Fearful Faces but Not Fearful Eyes Alone Delay Attention Disengagement in 7-Month-Old Infants

Adult-like attentional biases toward fearful faces can be observed in 7-month-old infants. It is possible, however, that infants merely allocate attention to simple features such as enlarged fearful eyes. In the present study, 7-month-old infants (n = 15) were first shown individual emotional faces to determine their visual scanning patterns of the expressions. Second, an overlap task was used to examine the latency of attention disengagement from centrally presented faces. In both tasks, the stimuli were fearful, happy, and neutral facial expressions, and a neutral face with fearful eyes. Eye tracking data from the first task showed that infants scanned the eyes more than other regions of the face, however, there were no differences in scanning patterns across expressions. In the overlap task, infants were slower in disengaging attention from fearful as compared to happy and neutral faces and also to neutral faces with fearful eyes. Together, these results provide evidence that threat-related stimuli tend to hold attention preferentially in 7-month-old infants and that the effect does not reflect a simple response to differentially salient eyes in fearful faces

Visual evoked potentials detect cortical processing deficits in Rett syndrome

ObjectiveRett syndrome (RTT) is a neurodevelopmental disorder caused by mutation of the X-linked MECP2 gene and characterized by developmental regression during the first few years of life. The objective of this study was to investigate if the visual evoked potential (VEP) could be used as an unbiased, quantitative biomarker to monitor brain function in RTT. MethodsWe recorded pattern-reversal VEPs in Mecp2 heterozygous female mice and 34 girls with RTT. The amplitudes and latencies of VEP waveform components were quantified, and were related to disease stage, clinical severity, and MECP2 mutation type in patients. Visual acuity was also assessed in both mice and patients by modulating the spatial frequency of the stimuli. ResultsMecp2 heterozygous female mice and RTT patients exhibited a similar decrease in VEP amplitude that was most striking in the later stages of the disorder. RTT patients also displayed a slower recovery from the principal peak of the VEP response that was impacted by MECP2 mutation type. When the spatial frequency of the stimulus was increased, both patients and mice displayed a deficit in discriminating smaller patterns, indicating lower visual spatial acuity in RTT. InterpretationVEP is a method that can be used to assess brain function across species and in children with severe disabilities like RTT. Our findings support the introduction of standardized VEP analysis in clinical and research settings to probe the neurobiological mechanism underlying functional impairment and to longitudinally monitor progression of the disorder and response to treatmen

Mean standard composite scores on the Mullen Scales of Early Learning MSEL for infants at low and high risk for autism.

<p>Standard deviation in parentheses.</p>*<p>Indicates significant at p<0.05.</p

Estimates of fixed and random effects from individual growth models in which ASD risk predicts initial status and the rate of change in spectral power in infants between 6 and 24 months.

<p>∼ p<.10; * p<.05; ** p<.01; *** p<.001.</p