Individuals with Williams syndrome (WS) demonstrate an abnormally positive social bias. However, the neural substrates of this hypersociability, i.e., positive attribution bias and increased drive toward social interaction, have not fully been elucidated. Methods: We performed an event-related functional magnetic resonance imaging study while individuals with WS and typically developing controls (TD) matched positive and negative emotional faces. WS compared to TD showed reduced right amygdala activation during presentation of negative faces, as in the previous literature. In addition, WS showed a unique pattern of right orbitofrontal cortex activation. While TD showed medial orbitofrontal cortex activation in response to positive, and lateral orbitofrontal cortex activation to negative, WS showed the opposite pattern. In light of the general notion of a medial/lateral gradient of reward/punishment processing in the orbitofrontal cortex, these findings provide an additional biological explanation for, or correlate of positive attribution bias and hypersociability in WS.

There is increasing evidence that genomic imprinting, a process by which certain genes are expressed in a parent-of-origin specific manner, can influence neurogenetic and psychiatric manifestations. While some data suggest possible imprinting effects of the X-chromosome on physical and cognitive characteristics in human, there is no compelling evidence that X-linked imprinting affects brain morphology. To address this issue, we investigated regional cortical volume, thickness and surface area in 27 healthy controls and 40 prepubescent girls with Turner syndrome (TS), a condition caused by the absence of one X-chromosome. Of the young girls with TS, 23 inherited their X-chromosome from their mother (Xm) and 17 from their father (Xp). Our results confirm the existence of significant differences in brain morphology between girls with TS and controls, and reveal the presence of a putative imprinting effect among the TS groups: girls with Xp demonstrated thicker cortex than those with Xm in the temporal regions bilaterally, while Xm individuals showed bilateral enlargement of gray matter volume in the superior frontal regions in comparison to Xp. These data suggest the existence of imprinting effects of the X-chromosome that influence both cortical thickness and volume during early brain development, and help to explain variability in cognitive and behavioral manifestations of TS with regard to the parental origin of the X-chromosome.

Number sense is believed to be critical for math development. It is putatively an implicitly learned skill and may therefore have limitations in terms of being explicitly trained, particularly in individuals with altered neurodevelopment. A case series study was conducted using an adaptive, computerized program that focused on number sense and general problem solving skills was designed to investigate training effects on performance as well as brain function in a group of children with Turner syndrome who are at risk for math difficulties and altered development of math-related brain networks. Standardized measurements of math and math-related cognitive skills as well as functional magnetic resonance imaging (fMRI) were used to assess behavioral and neurobiologic outcomes following training. Participants demonstrated significantly increased basic math skills, including number sense, and calculation as well as processing speed, cognitive flexibility and visual-spatial processing skills. With the exception of calculation, increased scores also were clinically significant (i.e. recovered) based on reliable change analysis. Participants additionally demonstrated significantly increased bilateral parietal lobe activation and decreased frontal-striatal and mesial temporal activation following the training program. These findings show proof of concept for an accessible training approach that may be potentially associated with improved number sense, math and related skills, as well as functional changes in math-related neural systems, even among individuals at risk for altered brain development.

Williams syndrome (WS) is a neurodevelopmental condition caused by a hemizygous deletion of ∼26-28 genes on chromosome 7q11.23. WS is associated with a distinctive pattern of social cognition. Accordingly, neuroimaging studies show that WS is associated with structural alterations of key brain regions involved in social cognition during adulthood. However, very little is currently known regarding the neuroanatomical structure of social cognitive brain networks during childhood in WS. This study used diffusion tensor imaging to investigate the structural integrity of a specific set of white matter pathways (inferior fronto-occipital fasciculus [IFOF] and uncinate fasciculus [UF]) and associated brain regions [fusiform gyrus (FG), amygdala, hippocampus, medial orbitofrontal gyrus (MOG)] known to be involved in social cognition in children with WS and a typically developing (TD) control group. Children with WS exhibited higher fractional anisotropy (FA) and axial diffusivity values and lower radial diffusivity and apparent diffusion coefficient (ADC) values within the IFOF and UF, higher FA values within the FG, amygdala, and hippocampus and lower ADC values within the FG and MOG compared to controls. These findings provide evidence that the WS genetic deletion affects the development of key white matter pathways and brain regions important for social cognition.

BACKGROUND: Although emergence from the minimally conscious state (eMCS) is associated with symptoms including disorientation, memory and attention impairment, restlessness, and significant functional disability, the neurobehavioral profile of eMCS has not been empirically characterized. OBJECTIVE: Determine degree of cognitive impairment, presence of clinical symptoms and functional disability at time eMCS in patients with traumatic and non-traumatic brain injury (TBI, nTBI). METHODS: Retrospective observational study of 169 adults (median [interquartile range] age: 51 [29, 62] years; male: 116; TBI: 103) who emerged from MCS based on the Coma Recovery Scale-Revised while in an inpatient Disorders of Consciousness program. Outcome measures include the Confusion Assessment Protocol (CAP) and Disability Rating Scale (DRS). RESULTS: CAP administration was attempted in 54 subjects. Twenty-eight subjects had valid scores on all CAP items, with a median [interquartile range] of 4 [3-5] symptoms of confusion. Scores in 93% of this subsample were consistent with an acute confusional state. The most common symptoms were cognitive impairment (98% of subjects), disorientation (93%), and agitation (69%). The median DRS score upon emergence from MCS was 14.5 [13, 16], indicating severe disability (n = 140). CONCLUSIONS: eMCS is associated with an acute confusional state and severe disability. This finding may inform the lower boundary of confusion as well as approach to treatment and caregiver education.