Reconstructing 3D Face of Infants in Social Interactions Using Morphable Models of Non-Infants.

3D morphable models (3DMMs) simultaneously reconstruct facial morphology, expression and pose from 2D images, and thus could be an invaluable tool for capturing and characterizing the face and facial behavior in early childhood. However, 3DMM fitting on infants is a largely unexplored problem. All publicly available 3DMMs are developed for adults, and it is unclear if and to what extent they can be used on videos of infants. In this paper, we compare five state-of-the-art 3DMM fitting methods on data from naturalistic infant-caregiver interactions. Results suggest that it is possible to produce consistent and subject-specific reconstructions of 3D shape identity from multiple frames, but not from a single frame. Qualitative evaluation highlights that facial regions with high texture variation, such as eyes, brows and mouth, are captured with higher accuracy compared to the rest of the face. Thus, even though a 3DMM developed for adults has significant limitations when reconstructing the morphology of the entire facial region of infants, applications that involve analysis of facial behavior can be feasible. Our encouraging results, combined with the unique ability of 3DMMs to disentangle two major sources of noise for expression analysis (i.e., identity bias and pose variations), motivate future research on using 3DMMs to measure the facial behavior of infants.

Infants later diagnosed with autism have lower canonical babbling ratios in the first year of life.

BACKGROUND: Canonical babbling-producing syllables with a mature consonant, full vowel, and smooth transition-is an important developmental milestone that typically occurs in the first year of life. Some studies indicate delayed or reduced canonical babbling in infants at high familial likelihood for autism spectrum disorder (ASD) or who later receive an ASD diagnosis, but evidence is mixed. More refined characterization of babbling in the first year of life in infants with high likelihood for ASD is needed. METHODS: Vocalizations produced at 6 and 12 months by infants (n = 267) taking part in a longitudinal study were coded for canonical and non-canonical syllables. Infants were categorized as low familial likelihood (LL), high familial likelihood diagnosed with ASD at 24 months (HL-ASD) or not diagnosed (HL-Neg). Language delay was assessed based on 24-month expressive and receptive language scores. Canonical babble ratio (CBR) was calculated by dividing the number of canonical syllables by the number of total syllables. Generalized linear (mixed) models were used to assess the relationship between group membership and CBR, controlling for site, sex, and maternal education. Logistic regression was used to assess whether canonical babbling ratios at 6 and 12 months predict 24-month diagnostic outcome. RESULTS: No diagnostic group differences in CBR were detected at 6 months, but HL-ASD infants produced significantly lower CBR than both the HL-Neg and LL groups at 12 months. HL-Neg infants with language delay also showed reduced CBR at 12 months. Neither 6- nor 12-month CBR was significant predictors of 24-month diagnostic outcome (ASD versus no ASD) in logistic regression. LIMITATIONS: Small numbers of vocalizations produced by infants at 6 months may limit the reliability of CBR estimates. It is not known if results generalize to infants who are not at high familial likelihood, or infants from more diverse racial and socioeconomic backgrounds. CONCLUSIONS: Lower canonical babbling ratios are apparent by the end of the first year of life in ASD regardless of later language delay, but are also observed for infants with later language delay without ASD. Canonical babbling may lack specificity as an early marker when used on its own.

Atypicalities of Gesture Form and Function in Autistic Adults.

While well-represented on clinical measures, co-speech gesture production has never been formally studied in autistic adults. Twenty-one verbally fluent autistic adults and 21 typically developing controls engaged in a controlled conversational task. Group differences were observed in both semantic/pragmatic and motoric features of spontaneously produced co-speech gestures. Autistic adults prioritized different functions of co-speech gesture. Specifically, they used gesture more than controls to facilitate conversational turn-taking, demonstrating a novel nonverbal strategy for regulating conversational dynamics. Autistic adults were more likely to gesture unilaterally than bilaterally, a motoric feature of gesture that was individually associated with autism symptoms. Co-speech gestures may provide a link between nonverbal communication symptoms and known differences in motor performance in autism.

Language delay aggregates in toddler siblings of children with autism spectrum disorder.

BACKGROUND: Language delay is extremely common in children with autism spectrum disorder (ASD), yet it is unclear whether measurable variation in early language is associated with genetic liability for ASD. Assessment of language development in unaffected siblings of children with ASD can inform whether decreased early language ability aggregates with inherited risk for ASD and serves as an ASD endophenotype. METHODS: We implemented two approaches: (1) a meta-analysis of studies comparing language delay, a categorical indicator of language function, and language scores, a continuous metric, in unaffected toddlers at high and low familial risk for ASD, and (2) a parallel analysis of 350 unaffected 24-month-olds in the Infant Brain Imaging Study (IBIS), a prospective study of infants at high and low familial risk for ASD. An advantage of the former was its detection of group differences from pooled data across unique samples; an advantage of the latter was its sensitivity in quantifying early manifestations of language delay while accounting for covariates within a single large sample. RESULTS: Meta-analysis showed that high-risk siblings without ASD (HR-noASD) were three to four times more likely to exhibit language delay versus low-risk siblings without ASD (LR-noASD) and had lower mean receptive and expressive language scores. Analyses of IBIS data corroborated that language delay, specifically receptive language delay, was more frequent in the HR-noASD (n = 235) versus LR-noASD group (n = 115). IBIS language scores were continuously and unimodally distributed, with a pathological shift towards decreased language function in HR-noASD siblings. The elevated inherited risk for ASD was associated with lower receptive and expressive language scores when controlling for sociodemographic factors. For receptive but not expressive language, the effect of risk group remained significant even when controlling for nonverbal cognition. CONCLUSIONS: Greater frequency of language delay and a lower distribution of language scores in high-risk, unaffected toddler-aged siblings support decreased early language ability as an endophenotype for ASD, with a more pronounced effect for receptive versus expressive language. Further characterization of language development is warranted to refine genetic investigations of ASD and to elucidate factors influencing the progression of core autistic traits and related symptoms.

Neural correlates of naturalistic social cognition: brain-behavior relationships in healthy adults.

Being able to infer the thoughts, feelings and intentions of those around us is indispensable in order to function in a social world. Despite growing interest in social cognition and its neural underpinnings, the factors that contribute to successful mental state attribution remain unclear. Current knowledge is limited because the most widely used tasks suffer from two main constraints: (i) They fail to capture individual variability due to ceiling effects and (ii) they use highly simplistic, often artificial stimuli inapt to mirror real-world socio-cognitive demands. In the present study, we address these problems by employing complex depictions of naturalistic social interactions that vary in both valence (positive vs negative) and ambiguity (high vs low). Thirty-eight healthy participants (20 female) made mental state judgments while brain responses were obtained using functional magnetic resonance imaging (fMRI). Accuracy varied based on valence and ambiguity conditions and women were more accurate than men with highly ambiguous social stimuli. Activity of the orbitofrontal cortex predicted performance in the high ambiguity condition. The results shed light on subtle differences in mentalizing abilities and associated neural activity.

Network inefficiencies in autism spectrum disorder at 24 months.

Autism spectrum disorder (ASD) is a developmental disorder defined by behavioral symptoms that emerge during the first years of life. Associated with these symptoms are differences in the structure of a wide array of brain regions, and in the connectivity between these regions. However, the use of cohorts with large age variability and participants past the generally recognized age of onset of the defining behaviors means that many of the reported abnormalities may be a result of cascade effects of developmentally earlier deviations. This study assessed differences in connectivity in ASD at the age at which the defining behaviors first become clear. There were 113 24-month-old participants at high risk for ASD, 31 of whom were classified as ASD, and 23 typically developing 24-month-old participants at low risk for ASD. Utilizing diffusion data to obtain measures of the length and strength of connections between anatomical regions, we performed an analysis of network efficiency. Our results showed significantly decreased local and global efficiency over temporal, parietal and occipital lobes in high-risk infants classified as ASD, relative to both low- and high-risk infants not classified as ASD. The frontal lobes showed only a reduction in global efficiency in Broca's area. In addition, these same regions showed an inverse relation between efficiency and symptom severity across the high-risk infants. The results suggest delay or deficits in infants with ASD in the optimization of both local and global aspects of network structure in regions involved in processing auditory and visual stimuli, language and nonlinguistic social stimuli.

Oxytocin plasma concentrations after single intranasal oxytocin administration - a study in healthy men.

The neuropeptide oxytocin has become a subject of great interest in studies investigating human social cognition. Single intranasal administration of the hormone has been reported to have positive behavioral effects, such as increasing trust or facilitating social approach, 45-80 min after administration. However, little is still known about the long-term pharmacokinetics of oxytocin nasal spray application in humans. This study addressed the question how long oxytocin plasma levels remain elevated following nasal spray administration. Another goal was to examine the influence of oxytocin administration on endogenous steroid hormones since such alterations might modulate social behavior via an indirect way. Eight healthy Caucasian men were challenged with a single intranasal application of 26 international units of oxytocin. Changes in oxytocin blood plasma levels, as well as steroid hormone levels of progesterone, testosterone and estradiol were assessed at 5 consecutive time points over a period of 3.5 h (-5, +30, +90, +150, +210 min relative to oxytocin administration). Results gave evidence for a substantial rise of oxytocin plasma levels 30 min after intranasal administration, observed in 7 of 8 participants. Group mean oxytocin plasma level was found to have returned to baseline already 90 min post administration, though in some individuals the plasma levels was still elevated relative to sampling at post 150 min. Steroid hormone analyses yielded a slight augmentation of endogenous testosterone levels 210 min after oxytocin administration. Our data confirms previous findings that oxytocin administered as a nasal spray enters the blood circulation, elevating oxytocin plasma levels for a limited time. Our findings suggest that this time window differs between individuals, but that, for the used dose, it does not extend beyond 150 min post administration. The data further provides preliminary evidence that intranasal oxytocin has an enhancing effect on testosterone in healthy men.

A placebo-controlled trial of risperidone in Tourette syndrome.

OBJECTIVE: To evaluate the efficacy and safety of risperidone in children and adults with Tourette syndrome. METHODS: This was an 8-week, randomized, double-blind, placebo-controlled trial. The primary outcome measure was the Total Tic score of the Yale Global Tic Severity Scale (YGTSS). RESULTS: Thirty-four medication-free subjects (26 children and 8 adults) ranging in age from 6 to 62 years (mean = 19.7 +/- 17.0 years) participated. YGTSS Total Tic scores were similar at baseline (26.0 +/- 5.1 for risperidone vs 27.4 +/- 8.5 for placebo). After 8 weeks of treatment (mean daily dose of 2.5 +/- 0.85), the 16 subjects on risperidone showed a 32% reduction in tic severity from baseline, compared to a 7% reduction for placebo patients (n = 18) (F[2,64] = 6.07; p = 0.004). The 12 children randomized to risperidone showed a 36% reduction in tic symptoms compared to an 11% decrease in the 14 children on placebo (F[2,48] = 6.38; p = 0.004). Two children on risperidone showed acute social phobia, which resolved with dose reduction in one subject but resulted in medication discontinuation in the other. A mean increase in body weight of 2.8 kg was observed in the risperidone group compared to no change in placebo (F[2,64] = 10.68; p = 0.0001). No extrapyramidal symptoms and no clinically significant alterations in cardiac conduction times or laboratory measures were observed. CONCLUSION: Risperidone appears to be safe and effective for short-term treatment of tics in children or adults with Tourette syndrome. Longer-term studies are needed to evaluate the durability of efficacy and safety over time.

A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder.

OBJECTIVE: This study evaluated the efficacy and safety of guanfacine in treating children with tic disorders and attention deficit hyperactivity disorder (ADHD). METHOD: Subjects from a specialty tic disorders clinic were randomly assigned to receive 8 weeks of treatment with guanfacine or placebo under double-blind conditions. Follow-up visits occurred every 2 weeks for safety monitoring and dose adjustment. RESULTS: Thirty-four medication-free subjects (31 boys and three girls with a mean age of 10.4 years) with ADHD, combined type, and a tic disorder participated. After 8 weeks of treatment, guanfacine was associated with a mean improvement of 37% in the total score on the teacher-rated ADHD Rating Scale, compared to 8% improvement for placebo. Nine of 17 subjects who received guanfacine were blindly rated on the Clinical Global Improvement scale as either much improved or very much improved, compared with none of 17 subjects who received placebo. The mean score on the parent-rated hyperactivity index improved by 27% in the guanfacine group and 21% in the placebo group, not a significant difference. On the Continuous Performance Test, commission errors decreased by 22% and omission errors by 17% in the guanfacine group, compared with increases of 29% in commission errors and of 31% in omission errors in the placebo group. Tic severity decreased by 31% in the guanfacine group, compared to 0% in the placebo group. One guanfacine subject with sedation withdrew at week 4. Guanfacine was associated with insignificant decreases in blood pressure and pulse. CONCLUSIONS: Guanfacine appears to be a safe and effective treatment for children with tic disorders and ADHD.

Abnormal ventral temporal cortical activity during face discrimination among individuals with autism and Asperger syndrome.

BACKGROUND: Recognition of individual faces is an integral part of both interpersonal interactions and successful functioning within a social group. Therefore, it is of considerable interest that individuals with autism and related conditions have selective deficits in face recognition (sparing nonface object recognition). METHOD: We used functional magnetic resonance imaging (fMRI) to study face and subordinate-level object perception in 14 high-functioning individuals with autism or Asperger syndrome (the autism group), in comparison with 2 groups of matched normal controls (normal control group ] [NC1] and normal control group 2 [NC2]) (n = 14 for each). Regions of interest (ROIs) were defined in NC1 and then applied in comparisons between NC2 and the autism group. Regions of interest were also defined in NC2 and then applied to comparisons between NC1 and the autism group as a replication study. RESULTS: In the first set of comparisons, we found significant task x group interactions for the size of activation in the right fusiform gyrus (FG) and right inferior temporal gyri (ITG). Post hoc analyses showed that during face (but not object) discrimination, the autism group had significantly greater activation than controls in the right ITG and less activation of the right FG. The replication study showed again that the autism group used the ITG significantly more for processing faces than the control groups, but for these analyses, the effect was now on the left side. Greater ITG activation was the pattern found in both control groups during object processing. CONCLUSIONS: Individuals with autism spectrum disorders demonstrate a pattern of brain activity during face discrimination that is consistent with feature-based strategies that are more typical of nonface object perception.

Social and emotional adjustment in children affected with Gilles de la Tourette's syndrome: associations with ADHD and family functioning. Attention Deficit Hyperactivity Disorder.

This study examined social-emotional functioning in children with Gilles de la Tourette's syndrome (TS) alone and children with TS and Attention Deficit Hyperactivity Disorder (ADHD). In addition, the contribution of family functioning to social competence was examined. Children with a clinical diagnosis of TS were recruited from the Yale Child Study Center TS specialty clinic. Unaffected control children were recruited through newspaper advertisements and announcements within the university and at area schools. The final sample consisted of 72 children (45 boys and 27 girls) between the ages of 8 and 14. Sixteen children met DMS-III-R criteria for TS, 33 children met criteria for TS and ADHD, and 23 children had no psychiatric diagnoses. Children with TS and ADHD evidenced more externalizing and internalizing behavior problems and poorer social adaptation than children with TS only or unaffected controls. Children with TS only were not significantly different from unaffected controls on most measures of externalizing behaviors and social adaptation but did exhibit more internalizing symptoms. Tic symptom severity was not associated with social, behavioral, or emotional functioning among children with TS, even after stratifying by medication status. However, ADHD diagnosis, obsessional symptom severity, and family functioning were significantly associated with social and emotional adjustment among TS children. Moreover, family functioning was associated with social and emotional adjustment even after controlling for TS and ADHD diagnostic status. These findings demonstrate that much of the social and behavioral dysfunction in children with TS is ADHD-specific and children with TS alone have a very different social-emotional profile than do those with TS plus ADHD. Finally, social-emotional adjustment in children with TS is best understood within the family context.

Neuropsychological models of childhood obsessive-compulsive disorder.

Neuropsychological models of obsessive-compulsive disorder (OCD) point to a fairly consistent pattern of deficits in response inhibition, visual memory, and visuoperceptual functioning. However, little is known about these areas of functioning with respect to child onset OCD because most studies to date have focused on adults. Data from adult OCD studies nevertheless provide valuable heuristic models of functioning that need to be systematically assessed in children. Moreover, combining neuro-psychological assessment with neuroimaging methods is a particularly powerful approach that promises to delineate the pathobiology of these disorders more precisely and to determine the degree of overlap between child and adult onset forms of OCD.

Segmentation and measurement of the cortex from 3-D MR images using coupled-surfaces propagation.

The cortex is the outermost thin layer of gray matter in the brain; geometric measurement of the cortex helps in understanding brain anatomy and function. In the quantitative analysis of the cortex from MR images, extracting the structure and obtaining a representation for various measurements are key steps. While manual segmentation is tedious and labor intensive, automatic reliable efficient segmentation and measurement of the cortex remain challenging problems, due to its convoluted nature. Here we present a new approach of coupled-surfaces propagation, using level set methods to address such problems. Our method is motivated by the nearly constant thickness of the cortical mantle and takes this tight coupling as an important constraint. By evolving two embedded surfaces simultaneously, each driven by its own image-derived information while maintaining the coupling, a final representation of the cortical bounding surfaces and an automatic segmentation of the cortex are achieved. Characteristics of the cortex, such as cortical surface area, surface curvature, and cortical thickness, are then evaluated. The level set implementation of surface propagation offers the advantage of easy initialization, computational efficiency, and the ability to capture deep sulcal folds. Results and validation from various experiments on both simulated and real three-dimensional (3-D) MR images are provided.

Lateral intertransverse process single-level fusion for salvage of the unstable failed posterior lumbar interbody fusion.

Our study was an attempt to salvage severely unstable posterior lumbar interbody fusions (PLIFs) by using the lateral bilateral intertransverse single-level (floating) fusion. A retrospective review of six patients with failed L4-L5 PLIFs was carried out. These patients underwent reoperation between 2 weeks and 2 years after the initial surgery. All patients had persistent symptoms, including low back pain and sciatica, interfering with activities of daily living. Computed tomography (CT) scans revealed extrusion of the bone plug into the spinal canal in five patients. All six had a nonunion of the PLIF, and three patients had grade 3 or 4 iatrogenic spondylolisthesis caused by the PLIF. The operation involved decompression followed by lateral intertransverse process fusion with autogenous bone graft. All patients were placed in external immobilization after the procedure for 3 months. Follow-up averaged 38.5 months (range, 21-55), at which time five had substantial pain improvement. Five were radiographically fused. One had a second nonunion, which subsequently healed after reoperation with repeat lateral fusion and Luque plate hardware. Our fusion rate was 83% without the use of instrumentation. In conclusion, we recommend the simplistic procedure of lateral bilateral intertransverse process single-level fusion along with liberal external immobilization for the difficult problem of salvage of failed PLIFs.

Brain morphology in normal and dyslexic children: the influence of sex and age.

Morphometric magnetic resonance imaging techniques were used to compare the convolutional surface area of the planum temporale, temporal lobe volume and superior surface area, and an estimate of overall brain volume in a homogeneous sample of 17 dyslexic children (7 girls) and 14 nonimpaired children (7 girls). Substantial sex differences were apparent for all measured regions, with all the measurements in boys being significantly larger. Age, even within the narrow range employed here (7.5-9.7 years), was positively correlated with the size of each brain region. While initial analyses suggested smaller left hemisphere structures in dyslexics compared to control subjects, subsequent analyses controlling for age and overall brain size revealed no significant differences between dyslexics and nonimpaired children on a variety of measures, in particular surface area and symmetry of the planum temporale. We suggest that differences in subject characteristics (i.e., sex, age, handedness, and definition of dyslexia) as well as procedural variations in the methods used to acquire images and to define and measure anatomical regions of interest such as the planum temporale all may play an important role in explaining apparent discrepant results in the neuroimaging literature on dyslexia.

Subjective utility ratings of neuroleptics in treating schizophrenia.

This study developed a method for measuring subjective costs and benefits of psychiatric treatments. Forty-one patients rates the relative bothersomeness of symptoms of schizophrenia and side effects of neuroleptics. Thirty-four psychiatrists made parallel ratings from the perspective of the average patient (individual utility) and of the patient's family and society (institutional utility). Psychiatrists predicted patients' ratings moderately well, but misjudged the bothersomeness to patients of 24% of side effects and 20% of symptoms. When considering the patient's perspective, both schizophrenic patients and psychiatrists rated symptoms as no more bothersome than side effects. However, psychiatrists saw side effects as significantly less bothersome than symptoms when considering costs to society. The subjective utility of neuroleptic medications for schizophrenia is most justifiable from an institutional perspective.

Nutrition and the rheumatoid hand patient.

The incidence of nutritional depletion in 40 rheumatoid patients and the factors that influence these patients' nutritional status were investigated. More than half of the patients (52.5%) were found to be nutritionally deficient.

Relation of the hepatic and splenic microcirculations to the development of lesions in experimental amyloidosis.

By the use of a perfusion technique for identifying blood vessels, it was found that amyloid lesions in mice have a close relation to the underlying microcirculation. The earliest lesions develop about arteriolar capillaries. With the onset of the lesions, circulation of plasma not only continues through the affected vessels but also extends into the entire volume of the surrounding lesions. Progression of the lesions follows the underlying microcirculation, and there is a continuing presence of circulating proteins. Other observations, from tracer studies using labeled plasma proteins and studies of unfixed, frozen, tissue sections following saline extraction, indicate that much of the early amyloid lesions in these animals is circulating plasma. It would appear that the onset and site of formation of the lesions is determined by arteriolar capillary injury rather than by polymorphism of SAA proteins. Structural amyloid fibril proteins may gain access to the lesions by either entry from the circulation or local formation.