Visual attention in autism families: ‘unaffected’ sibs share atypical frontal activation

Background: In addition to their more clinically evident abnormalities of social cognition, people with autism spectrum conditions (ASC) manifest perturbations of attention and sensory perception which may offer insights into the underlying neural abnormalities. Similar autistic traits in ASC relatives without a diagnosis suggest a continuity between clinically affected and unaffected family members

Sex differences in the brain: implications for explaining autism

‘Empathizing’ is the capacity to predict and to respond to the behavior of agents (usually people) by inferring their mental states and responding to these with an appropriate emotion. ‘Systemizing’ is the capacity to predict and to respond to the behavior of non-agentive, deterministic systems, by analyzing input-operation-output relations and inferring the rules that govern such systems. At a population level, females are stronger empathizers and males stronger systemizers. The ‘extreme male brain’ theory posits that autism represents an extreme of the male pattern (impaired empathizing and enhanced systemizing). Here we suggest that specific aspects of autistic neuropathology may also be extremes of typical male neuroanatomy

Neural endophenotypes of social behaviour in autism spectrum conditions

Autism is characterized by qualitative impairments in social interaction, communication, and stereotyped repetitive behaviors and/or restricted interests. Beyond these diagnostic criteria, autism is viewed as a neurodevelopmental condition with possibly several etiologies that manifest in complex patterns of atypical structural and functional brain development, cognition, and behavior. Despite the multidimensional nature of and substantial variation within the autism spectrum, impairments in social interaction remain among the most visible hallmarks of the condition. It is this profound developmental deficit in the social domain that makes autism a unique case in the field of social neuroscience. This chapter contributes to the dialogue amongst both the fields of autism research and social neuroscience by deliberately taking the stance of asking how we can understand more about the etiological mechanisms underlying social behavior in autism. It presents a multi-level overview of the literature on the behavioral, neural, and genetic underpinnings of social functioning in autism spectrum conditions (ASC). The main objective is to highlight the current state of the field regarding theory of mind/empathy difficulties in ASC, and then to suggest distinct candidate neural endophenotypes that can bridge the gap between social behavior and genetic mechanisms

Change detection in children with autism: an auditory event-related fMRI study

Autism involves impairments in communication and social interaction, as well as high levels of repetitive, stereotypic and ritualistic behaviours, and extreme resistance to change. This latter dimension, whilst required for a diagnosis, has received less research attention. We hypothesise that this extreme resistance to change in autism is rooted in atypical processing of unexpected stimuli. We tested this using auditory event-related fMRI to determine regional brain activity associated with passive detection of infrequently occurring frequency-deviant and complex novel sounds in a no-task condition. Participants were twelve 10 to 15-year-old children with autism, and a group of 12 age- and sex-matched healthy controls

Protection of rat renal vitamin E levels by ischemic-preconditioning

BACKGROUND: During renal transplantation, the kidney remains without blood flow for a period of time. The following reperfusion of this ischemic kidney causes functional and structural injury. Formation of oxygen-derived free radicals (OFR) and subsequent lipid peroxidation (LP) has been implicated as the causative factors of these injuries. Vitamin E is known to be the main endogenous antioxidant that stabilizes cell membranes by interfering with LP. The present study was designed to examine the role of ischemic-preconditioning (repeated brief periods of ischemia, IPC) in prevention of renal injury caused by ischemia-reperfusion (IR) in rats. METHODS: IPC included sequential clamping of the right renal artery for 5 min and release of the clamp for another 5 min for a 3 cycles. IR was induced by 30 min ischemia followed by 10 min reperfusion. Four groups of male rats were used: Control, IPC, IR and IPC-IR. Vitamin E, an endogenous antioxidant and as an index of LP, was measured by HPLC and UV detection in renal venous plasma and tissue. Renal function was assessed by serum creatinine and BUN levels. Renal damage was assessed in sections stained with Haematoxylin and Eosin. RESULTS: In the IR group, there was a significant decrease in vitamin E in plasma and tissue compared to a control group (p,0.05). In the IPC-IR group, vitamin E concentration was significantly higher than in the IR group (p,0.01). The results showed that 30 min ischemia in the IR group significantly (p,0.05) reduced renal function demonstrated by an increase in serum creatinine levels as compared with the control group. These results in the IPC group also showed a significant difference with the IR group but no significant difference in serum BUN and creatinine between IR and IPC-IR group were detected. Histological evaluation showed no structural damage in the IPC group and an improvement in the IPC-IR group compared to IR alone. CONCLUSIONS: In this study, IPC preserved vitamin E levels, but it could not markedly improve renal function in the early phase (1–2 h) of reperfusion. IPC may be a useful method for antioxidant preservation in organ transplantation

Recognition memory, self-other source memory, and theory-of-mind in children with autism spectrum disorder.

This study investigated semantic and episodic memory in autism spectrum disorder (ASD), using a task which assessed recognition and self-other source memory. Children with ASD showed undiminished recognition memory but significantly diminished source memory, relative to age- and verbal ability-matched comparison children. Both children with and without ASD showed an “enactment effect”, demonstrating significantly better recognition and source memory for self-performed actions than other-person-performed actions. Within the comparison group, theory-of-mind (ToM) task performance was significantly correlated with source memory, specifically for other-person-performed actions (after statistically controlling for verbal ability). Within the ASD group, ToM task performance was not significantly correlated with source memory (after controlling for verbal ability). Possible explanations for these relations between source memory and ToM are considered

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Is there a role for expectation maximization imputation in addressing missing data in research using WOMAC questionnaire? Comparison to the standard mean approach and a tutorial

<p>Abstract</p> <p>Background</p> <p>Standard mean imputation for missing values in the Western Ontario and Mc Master (WOMAC) Osteoarthritis Index limits the use of collected data and may lead to bias. Probability model-based imputation methods overcome such limitations but were never before applied to the WOMAC. In this study, we compare imputation results for the Expectation Maximization method (EM) and the mean imputation method for WOMAC in a cohort of total hip replacement patients.</p> <p>Methods</p> <p>WOMAC data on a consecutive cohort of 2062 patients scheduled for surgery were analyzed. Rates of missing values in each of the WOMAC items from this large cohort were used to create missing patterns in the subset of patients with complete data. EM and the WOMAC's method of imputation are then applied to fill the missing values. Summary score statistics for both methods are then described through box-plot and contrasted with the complete case (CC) analysis and the true score (TS). This process is repeated using a smaller sample size of 200 randomly drawn patients with higher missing rate (5 times the rates of missing values observed in the 2062 patients capped at 45%).</p> <p>Results</p> <p>Rate of missing values per item ranged from 2.9% to 14.5% and 1339 patients had complete data. Probability model-based EM imputed a score for all subjects while WOMAC's imputation method did not. Mean subscale scores were very similar for both imputation methods and were similar to the true score; however, the EM method results were more consistent with the TS after simulation. This difference became more pronounced as the number of items in a subscale increased and the sample size decreased.</p> <p>Conclusions</p> <p>The EM method provides a better alternative to the WOMAC imputation method. The EM method is more accurate and imputes data to create a complete data set. These features are very valuable for patient-reported outcomes research in which resources are limited and the WOMAC score is used in a multivariate analysis.</p

Visuo-tactile integration in autism: atypical temporal binding may underlie greater reliance on proprioceptive information

BackgroundEvidence indicates that social functioning deficits and sensory sensitivities in autism spectrum disorder (ASD) are related to atypical sensory integration. The exact mechanisms underlying these integration difficulties are unknown; however, two leading accounts are (1) an over-reliance on proprioception and (2) atypical visuo-tactile temporal binding. We directly tested these theories by selectively manipulating proprioceptive alignment and visuo-tactile synchrony to assess the extent that these impact upon body ownership.MethodsChildren with ASD and typically developing controls placed their hand into a multisensory illusion apparatus, which presented two, identical live video images of their own hand in the same plane as their actual hand. One virtual hand was aligned proprioceptively with the actual hand (the veridical hand), and the other was displaced to the left or right. While a brushstroke was applied to the participants’ actual (hidden) hand, they observed the two virtual images of their hand also being stroked and were asked to identify their real hand. During brushing, one of three different temporal delays was applied to either the displaced hand or the veridical hand. Thus, only one virtual hand had synchronous visuo-tactile inputs.ResultsResults showed that visuo-tactile synchrony overrides incongruent proprioceptive inputs in typically developing children but not in autistic children. Evidence for both temporally extended visuo-tactile binding and a greater reliance on proprioception are discussed.ConclusionsThis is the first study to provide definitive evidence for temporally extended visuo-tactile binding in ASD. This may result in reduced processing of amodal inputs (i.e. temporal synchrony) over modal-specific information (i.e. proprioception). This would likely lead to failures in appropriately binding information from related events, which would impact upon sensitivity to sensory stimuli, body representation and social processes such as empathy and imitation