Sophia Vinci-Booher

Alcohol-induced facial dysmorphology in C57BL/6 mouse models of fetal alcohol spectrum disorder

Alcohol consumption during pregnancy causes fetal alcohol spectrum disorder (FASD), which includes a range of developmental deficits. Fetal alcohol syndrome is the most severe form of FASD and can be diagnosed with pathognomonic facial features such as a smooth philtrum, short palpebral fissure, and thin upper vermilion. However, many children with developmental damage because of prenatal alcohol exposure exhibit none, or only a subset, of the above features, making diagnosis difficult. This study explored novel analyses to quantify the effect of a known dose of alcohol on specific facial measurements in substrains C57BL/B6J (B6J) and C57BL/6NHsd (B6N) mice. Mouse dams were provided alcohol (Alc) consisting of 4.8% (vol/vol) alcohol in a liquid diet for 16 days prepregnancy and chow and water diet during mating, and then the alcohol liquid diet was reinstated on gestational days 7 (E7) to gestational day 17 (E17). Treatment controls included a pair-fed (PF) group given matched volumes of an alcohol-free liquid diet made isocalorically and a group given ad lib access to lab chow and water (Chow). Maternal diet intake (Alc and PF), blood alcohol concentrations (BACs), embryo weights, and 15 morphometric facial measurements for E17 embryos were analyzed. B6N dams drank more alcohol during pregnancy and generated higher BAC than B6J dams. Both the Alc and PF treatments induced significant reductions in embryo weights relative to Chow in both substrains. Alcohol treatments produced significant changes, relative to controls, in 4 of the 15 facial measures for the B6N substrain but only in two measures for the B6J substrain. Discriminant analysis demonstrated successful classification of the alcohol-exposed versus nonalcohol-exposed B6N embryos, with a high sensitivity of 86%, specificity 80%, and overall classification (total correct 83%), whereas B6J mice yielded sensitivity of 80%, specificity 78%, and overall correct classification in 79%. In addition, B6N mice showed significantly more effects of pair feeding on these facial measures than did B6J mice, suggesting that the B6N substrain may be more vulnerable to nutritional stress during pregnancy. Overall, these data indicate that both B6N and B6J mice were vulnerable to alcohol but show differences in the severity and location of alcohol-induced dysmorphic facial features and may parallel findings from human studies comparing different ethnic groups. Furthermore, these findings suggest that discriminant analysis may be useful in predicting alcohol exposure in either mouse substrains.

Relation Over Time Between Facial Measurements and Cognitive Outcomes in Fetal Alcohol-Exposed Children

BACKGROUND The identification of individuals exposed prenatally to alcohol can be challenging, with only those having the characteristic pattern of facial features, central nervous system abnormality, and growth retardation receiving a clinical diagnosis of fetal alcohol syndrome (FAS). METHODS Seventeen anthropometric measurements were obtained at 5 and 9 years from 125 Cape Town, South African children, studied since birth. The children were divided into 3 groups: FAS or partial FAS (PFAS), heavily exposed nonsyndromal (HE), and non-alcohol-exposed controls (C). Anthropometric measurements were evaluated for mean group differences. Logistic regression models were used to identify the subset of anthropometric measures that best predicted group membership. Anthropometric measurements were examined at the 2 ages in relation to prenatal alcohol exposure obtained prospectively from the mothers during pregnancy. Correlation of these facial measurements with key neurobehavioral outcomes including Wechsler Intelligence Scales for Children-IV IQ and eyeblink conditioning was used to assess their utility as indicators of alcohol-related central nervous system impairment. RESULTS Significant group differences were found for the majority of the anthropometric measures, with means of these measures smaller in the FAS/PFAS compared with HE or C. Upper facial widths, ear length, lower facial depth, and eye widths were consistent predictors distinguishing those exposed to alcohol from those who were not. Using longitudinal data, unique measures were identified that predicted facial anomalies at one age but not the other, suggesting the face changes as the individual matures. And 41% of the FAS/PFAS group met criteria for microtia at both ages. Three of the predictive anthropometric measures were negatively related to measures of prenatal alcohol consumption, and all were positively related to at least 1 neurobehavioral outcome. CONCLUSIONS The analysis of longitudinal data identified a common set of predictors, as well as some that are unique at each age. Prenatal alcohol exposure appears to have its primary effect on brain growth, reflected by smaller forehead widths, and may suppress neural crest migration to the branchial arches, reflected by deficits in ear length and mandibular dimensions. These results may improve diagnostic resolution and enhance our understanding of the relation between the face and the neuropsychological deficits that occur.

Visual-motor functional connectivity in preschool children emerges after handwriting experience

Abstract Handwriting letters has been shown to increase Blood Oxygen Level Dependent (BOLD) signal during letter perception in visual and motor brain regions relative to other types of training in preschool children. However, co-activation in these regions speaks neither to the presence of functional connections between them nor to the experiences by which such connections might be established. We investigated functional connectivity by applying generalized psychophysiological interactions analysis to BOLD data obtained from 4 to 6 year-old children after learning symbols through handwriting, tracing, or typing. Functional connections between (1) visual and parietal regions increased after all training conditions, (2) visual and ventral frontal regions increased after handwriting training with letters more than shapes, and (3) visual and dorsal frontal motor regions increased more after handwriting than typing letters. We conclude that visual-motor training creates functional connections among visual and motor brain regions that reflect different aspects of the handwriting experience.

The impact of multimodal-multisensory learning on human performance and brain activation patterns

The human brain is inherently a multimodal-multisensory dynamic learning system. All information that is processed by the brain must first be encoded through sensory systems and this sensory input can only be attained through motor movement. Although each sensory modality processes different signals from the environment in qualitatively different ways (e.g., sound waves, light waves, pressure, etc.), these signals are transduced into a common language in the brain. The signals are then associated and combined to produce our phenomenology of a coherent world. Therefore, the brain processes a seemingly unlimited amount of multisensory information for the purpose of interacting with the world. This interaction with the world, through the body, is multimodal. The body allows one to affect the environment through multiple motor movements (hand movements, locomotion, speech, gestures, etc.). These various actions, in turn, shape the multisensory input that the brain will subsequently receive. The feedforward-feedback loop that occurs every millisecond among sensory and motor systems is a reflection of these multisensory and multimodal interactions among the brain, body, and environment. As an aid to comprehension, readers are referred to this chapters Focus Questions and to the Glossary for a definition of terminology. In the following, we begin by delving deeper into how sensory signals are transduced in the brain and how multimodal activity shapes signal processing. We then provide samples of research that have demonstrated that multimodal interactions with the world, through action, facilitate learning. An overview of research on performance measured by overt behavioral responses in adult and developing populations is followed by examples of research on the effects that multimodal learning has on brain plasticity in adults and children. Together, the behavioral and neuroimaging literature underscore the importance of learning through multimodalmultisensory interactions throughout human development.

Neural substrates of sensorimotor processes: letter writing and letter perception

Writing and perceiving letters are thought to share similar neural substrates; however, what constitutes a neural representation for letters is currently debated. One hypothesis is that letter representation develops from sensorimotor experience resulting in an integrated set of modality-specific regions, whereas an alternative account suggests that letter representations may be abstract, independent of modality. Studies reviewed suggest that letter representation consists of a network of modality-responsive brain regions that may include an abstract component.

Facial image classification of mouse embryos for the animal model study of fetal alcohol syndrome

Fetal Alcohol Syndrome (FAS) is a developmental disorder caused by maternal drinking during pregnancy. Computerize imaging techniques have been applied to study human facial dysmorphology associated with FAS. This paper describes a new facial image analysis method based on a multi-angle image classification technique using micro-video images of mouse embryo. Images taken from several different angles are analyzed separately, and the results are combined for classifications that separate embryos with and without alcohol exposures. Analysis results from animal models provide critical references for the understanding of FAS and potential therapy solutions for human patients.

An Analysis of the Brain Systems Involved with Producing Letters by Hand

Complex visual–motor behaviors dominate human–environment interactions. Letter production, writing individual letters by hand, is an example of a complex visual–motor behavior composed of numerous behavioral components, including the required motor movements and the percepts that those motor movements create. By manipulating and isolating components of letter production, we provide experimental evidence that this complex visual–motor behavior is supported by a widespread neural system that is composed of smaller subsystems related to different sensorimotor components. Adult participants hand-printed letters with and without “ink” on an MR-safe digital writing tablet, perceived static and dynamic representations of their own handwritten letters, and perceived typeface letters during fMRI scanning. Our results can be summarized by three main findings: (1) Frontoparietal systems were associated with the motor component of letter production, whereas temporo-parietal systems were more associated with the visual component. (2) The more anterior regions of the left intraparietal sulcus were more associated with the motor component, whereas the more posterior regions were more associated with the visual component, with an area of visual–motor overlap in the posterior intraparietal sulcus. (3) The left posterior intraparietal sulcus and right fusiform gyrus responded similarly to both visual and motor components, and both regions also responded more during the perception of ones own handwritten letters compared with perceiving typed letters. These findings suggest that the neural systems recruited during complex visual–motor behaviors are composed of a set of interrelated sensorimotor subsystems that support the full behavior in different ways and, furthermore, that some of these subsystems can be rerecruited during passive perception in the absence of the full visual–motor behavior.