Aberrant brain activation during gaze processing in boys with fragile X syndrome.

Context: Eye contact is a fundamental component of human social behavior. Individuals with fragile X syndrome (fraX), particularly male subjects, avoid eye contact and display other social deficits. To date (to our knowledge), this behavior in fraX has been studied only in female subjects, who show lesser degrees of gaze aversion.

Association between cerebral shape and social use of language in Williams syndrome.

Williams syndrome (WS) is a neurogenetic disorder resulting from a hemizygous microdeletion at band 7q11.23. It is characterized by aberrant development of the brain and a unique profile of cognitive and behavioral features.

Neuroanatomical abnormalities in adolescents with attention-deficit/hyperactivity disorder.

Objective: Several neuroanatomic abnormalities have been reported in patients with attention-deficit/hyperactivity disorder (ADHD). However, findings are not always consistent, perhaps because of heterogeneous subject samples. Studying youths with documented familial ADHD provides an opportunity to examine a more homogeneous population.

Morphometric spatial patterns differentiating boys with fragile X syndrome, typically developing boys, and developmentally delayed boys aged 1 to 3 years.

Context: Brain maturation starts well before birth and occurs as a unified process with developmental interaction among different brain regions. Gene and environment play large roles in such a process. Studies of individuals with genetic disorders such as fragile X syndrome (FXS), which is a disorder caused by a single gene mutation resulting in abnormal dendritic and synaptic pruning, together with healthy individuals may provide valuable information.

Anomalous hypothalamic responses to humor in cataplexy.

Background: Cataplexy is observed in a subset of patients with narcolepsy and affects approximately 1 in 2,000 persons. Cataplexy is most often triggered by strong emotions such as laughter, which can result in transient, yet debilitating, muscle atonia. The objective of this study was to examine the neural systems underlying humor processing in individuals with cataplexy.

Neural phenotypes of common and rare genetic variants.

Neuroimaging methods offer a powerful way to bridge the gaps between genes, neurobiology and behavior. Such investigations may be further empowered by complementary strategies involving chromosomal abnormalities associated with particular neurobehavioral phenotypes, which can help to localize causative genes and better understand the genetics of complex traits in the general population. Here we review the evidence from studies using these convergent approaches to investigate genetic influences on brain structure: (1) studies of common genetic variations associated with particular neuroanatomic phenotypes, and (2) studies of possible 'genetic subtypes' of neuropsychiatric disorders with very high penetrance, with a focus on neuroimaging studies using novel computational brain mapping algorithms.

Longitudinal changes in intellectual development in children with Fragile X syndrome.

Structural equation modeling (SEM) was used to examine the development of intellectual functioning in 145 school-age pairs of siblings. Each pair included one child with Fragile X syndrome (FXS) and one unaffected sibling. All pairs of children were evaluated on the Wechsler Intelligence Scale for Children-Third Edition (WISC-III) at time 1 and 80 pairs of children received a second evaluation at time 2 approximately 4 years later.

Brain volume reductions within multiple cognitive systems in male preterm children at age twelve.

Objectives: To more precisely examine regional and subregional microstructural brain changes associated with preterm birth.

Study Design: We obtained brain volumes from 29 preterm children, age 12 years, with no ultrasound scanning evidence of intraventricular hemorrhage or cystic periventricular leukomalacia in the newborn period, and 22 age- and sex-matched term control subjects.

Results: Preterm male subjects demonstrated significantly lower white matter volumes in bilateral cingulum, corpus callosum, corticospinal tract, prefrontal cortex, superior and inferior longitudinal fasciculi compared with term male subjects.

Persistent default-mode network connectivity during light sedation.

The default-mode network (DMN) is a set of specific brain regions whose activity, predominant in the resting-state, is attenuated during cognitively demanding, externally-cued tasks. The cognitive correlates of this network have proven difficult to interrogate, but one hypothesis is that regions in the network process episodic memories and semantic knowledge integral to internally-generated mental activity. Here, we compare default-mode functional connectivity in the same group of subjects during rest and conscious sedation with midazolam, a state characterized by anterograde amnesia and a reduced level of consciousness.

Gender differences in the mesocorticolimbic system during computer game-play.

Little is known about the underlying neural processes of playing computer/video games, despite the high prevalence of its gaming behavior, especially in males. In a functional magnetic resonance imaging study contrasting a space-infringement game with a control task, males showed greater activation and functional connectivity compared to females in the mesocorticolimbic system. These findings may be attributable to higher motivational states in males, as well as gender differences in reward prediction, learning reward values and cognitive state during computer video games.

Autism and the development of face processing.

Autism is a pervasive developmental condition, characterized by impairments in non-verbal communication, social relationships and stereotypical patterns of behavior. A large body of evidence suggests that several aspects of face processing are impaired in autism, including anomalies in gaze processing, memory for facial identity and recognition of facial expressions of emotion. In search of neural markers of anomalous face processing in autism, much interest has focused on a network of brain regions that are implicated in social cognition and face processing.

Compulsive, self-injurious, and autistic behavior in children and adolescents with fragile X syndrome.

Compulsive, self-injurious, and autistic behaviors were examined in 31 boys and 29 girls with fragile X syndrome aged 5 to 20 years. Self-injurious behavior occurred in 58% of boys and 17% of girls, whereas compulsive behavior occurred in 72% of boys and 55% of girls and did not appear to be associated with self-injurious behavior. Fifty percent of boys and 20% of girls met diagnostic criteria for autism on the ADOS-G.

More is not always better: increased fractional anisotropy of superior longitudinal fasciculus associated with poor visuospatial abilities in Williams syndrome.

We used diffusion tensor imaging to examine white matter integrity in the dorsal and ventral streams among individuals with Williams syndrome (WS) compared with two control groups (typically developing and developmentally delayed) and using three separate analysis methods (whole brain, region of interest, and fiber tractography). All analysis methods consistently showed that fractional anisotropy (FA; a measure of microstructural integrity) was higher in the right superior longitudinal fasciculus (SLF) in WS compared with both control groups. There was a significant association with deficits in visuospatial construction and higher FA in WS individuals.

Brain, skull, and cerebrospinal fluid volumes in adult posttraumatic stress disorder.

Children and adolescents with maltreatment-related posttraumatic stress disorder (PTSD) exhibit smaller intracranial tissue volume than controls. Linear relationships have also been observed between intracranial tissue volume and the age of maltreatment onset. The authors explored associations among adult PTSD, early trauma, and cerebral volumes in 99 combat veterans.

Neuroanatomy of fragile X syndrome is associated with aberrant behavior and the fragile X mental retardation protein (FMRP).

Objective: To determine how neuroanatomic variation in children and adolescents with fragile X syndrome is linked to reduced levels of the fragile X mental retardation-1 protein and to aberrant cognition and behavior.

Methods: This study included 84 children and adolescents with the fragile X full mutation and 72 typically developing control subjects matched for age and sex. Brain morphology was assessed with volumetric, voxel-based, and surface-based modeling approaches.

Craniofacioskeletal syndrome: an X-linked dominant disorder with early lethality in males.

A syndrome with multisystem manifestations has been observed in three generations of a Caucasian family. The findings in seven females provide a composite clinical picture of microcephaly, short stature, small retroverted ears, full tip of the nose overhanging the columella, short philtrum, thin upper lip, soft tissue excrescences at the angle of the mouth, small mandible, small hands and feet with brachydactyly, finger V clinodactyly, flat feet, an excessive number of fingerprint arches, and mild impairment of cognitive function. Two males were more severely affected and died in the initial months of life.

Developmental trajectories of brain structure in adolescents with 22q11.2 deletion syndrome: a longitudinal study.

The 22q11.2 deletion syndrome (22q11.2DS) is associated with very high rates of schizophrenia-like psychosis and cognitive deficits.

ADHD- and medication-related brain activation effects in concordantly affected parent-child dyads with ADHD.

Background: Several studies have documented fronto-striatal dysfunction in children and adolescents with attention deficit/hyperactivity disorder (ADHD) using response inhibition tasks. Our objective was to examine functional brain abnormalities among youths and adults with ADHD and to examine the relations between these neurobiological abnormalities and response to stimulant medication.

Method: A group of concordantly diagnosed ADHD parent-child dyads was compared to a matched sample of normal parent-child dyads.

Posttraumatic stress symptoms and brain function during a response-inhibition task: an fMRI study in youth.

Youth who experience interpersonal trauma and have posttraumatic stress symptoms (PTSS) can exhibit difficulties in executive function and physiological hyperarousal. Response inhibition has been identified as a core component of executive function. In this study, we investigate the functional neuroanatomical correlates of response inhibition in youth with PTSS.

Prediction of children's reading skills using behavioral, functional, and structural neuroimaging measures.

The ability to decode letters into language sounds is essential for reading success, and accurate identification of children at high risk for decoding impairment is critical for reducing the frequency and severity of reading impairment. We examined the utility of behavioral (standardized tests), and functional and structural neuroimaging measures taken with children at the beginning of a school year for predicting their decoding ability at the end of that school year. Specific patterns of brain activation during phonological processing and morphology, as revealed by voxel-based morphometry (VBM) of gray and white matter densities, predicted later decoding ability.

Fragile X syndrome: assessment and treatment implications.

Fragile X syndrome (FraX) is the most common known cause of inherited mental impairment. FMR1 gene mutations, the cause of FraX, lead to reduced expression of FMR1 protein and an increased risk for a particular profile of cognitive, behavioral, and emotional dysfunction. The study of individuals with FraX provides a unique window of understanding into important disorders such as autism, social phobia, cognitive disability, and depression.

Reduced parietal and visual cortical activation during global processing in Williams syndrome.

Several lines of investigation suggest that individuals with Williams syndrome (WS), a neurodevelopmental disorder of well-characterized genetic etiology, have selective impairments in integrating local image elements into global configurations. We compared global processing abilities in 10 clinically and genetically diagnosed participants with WS (eight females, two males; mean age 31y 10mo [SD 9y 7mo], range 15y 5mo-48y 4mo) with a typically developed (TD) age- and sex-matched comparison group (seven females, one male; mean age 35y 2mo [SD 10y 10mo], range 24y-54y 7mo) using functional magnetic resonance imaging (fMRI). Behavioral data showed participants with WS to be significantly less accurate (p<0.

3D pattern of brain abnormalities in Williams syndrome visualized using tensor-based morphometry.

Unlabelled: Williams syndrome (WS) is a neurodevelopmental disorder associated with deletion of approximately 20 contiguous genes in chromosome band 7q11.23. Individuals with WS exhibit mild to moderate mental retardation, but are relatively more proficient in specific language and musical abilities.