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1.  Influence of the COMT val108/158met polymorphism on Continuous Performance Task Indices 
Neuropsychologia  2014;61:45-55.
The Continuous Performance Task (CPT) is a widely-used measure of sustained attention and impulsivity. Deficits in CPT performance have been found in several psychiatric disorders, such as Attention-Deficit/hyperactivity disorder (ADHD) and schizophrenia. Molecular genetic studies of CPT performance are currently limited and have generally revealed inconsistent findings. The current study tested the associations of the COMT val108/158met polymorphism with AX-CPT indices (i.e., omission and commission errors, d′, and lnβ), as well as the variability of these indices across blocks, in a sample of clinic-referred and non-referred children (N = 380). We found significant associations between COMT and variability in the Signal Detection Theory (SDT) indices d′ and lnβ across blocks, as well as a statistical trend for association between COMT and commission errors. Higher externalizing psychopathology was associated with general impairment on AX-CPT performance, and for some indices (i.e., d′ variability and lnβ variability) the effect of COMT was stronger at higher levels of psychopathology. Our findings support the role of COMT in components of CPT performance and highlight the potential utility of using SDT indices, particularly in relation to variability in performance. Moreover, our results suggest that for some indices the effect of COMT is stronger at higher levels of externalizing psychopathology. Our study yields some preliminary insights regarding the neurobiology of CPT performance, which may elucidate the mechanisms by which specific genes confer risk for various cognitive deficits, as well as relevant disorders characterized by these deficits.
PMCID: PMC4122640  PMID: 24946318
COMT; Dopamine; Continuous Performance Task; CPT; Endophenotype; ADHD
2.  Abnormal autonomic and associated brain activities during rest in autism spectrum disorder 
Brain  2014;137(1):153-171.
Autism spectrum disorders are associated with social and emotional deficits, the aetiology of which are not well understood. A growing consensus is that the autonomic nervous system serves a key role in emotional processes, by providing physiological signals essential to subjective states. We hypothesized that altered autonomic processing is related to the socio-emotional deficits in autism spectrum disorders. Here, we investigated the relationship between non-specific skin conductance response, an objective index of sympathetic neural activity, and brain fluctuations during rest in high-functioning adults with autism spectrum disorder relative to neurotypical controls. Compared with control participants, individuals with autism spectrum disorder showed less skin conductance responses overall. They also showed weaker correlations between skin conductance responses and frontal brain regions, including the anterior cingulate and anterior insular cortices. Additionally, skin conductance responses were found to have less contribution to default mode network connectivity in individuals with autism spectrum disorders relative to controls. These results suggest that autonomic processing is altered in autism spectrum disorders, which may be related to the abnormal socio-emotional behaviours that characterize this condition.
PMCID: PMC3891443  PMID: 24424916
autism; autonomic nervous system; emotion; skin conductance; resting state
3.  Preclinical Efficacy and Mechanisms of Mesenchymal Stem Cells in Animal Models of Autoimmune Diseases 
Immune Network  2014;14(2):81-88.
Mesenchymal stem cells (MSCs) are present in diverse tissues and organs, including bone marrow, umbilical cord, adipose tissue, and placenta. MSCs can expand easily in vitro and have regenerative stem cell properties and potent immunoregulatory activity. They inhibit the functions of dendritic cells, B cells, and T cells, but enhance those of regulatory T cells by producing immunoregulatory molecules such as transforming growth factor-β, hepatic growth factors, prostaglandin E2, interleukin-10, indolamine 2,3-dioxygenase, nitric oxide, heme oxygenase-1, and human leukocyte antigen-G. These properties make MSCs promising therapeutic candidates for the treatment of autoimmune diseases. Here, we review the preclinical studies of MSCs in animal models for systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease, and experimental autoimmune encephalomyelitis, and summarize the underlying immunoregulatory mechanisms.
PMCID: PMC4022782  PMID: 24851097
Mesenchymal stem cells; Immunoregulation; Autoimmune diseases
4.  Cue contrast modulates the effects of exogenous attention on appearance 
Vision research  2009;49(14):1825-1837.
Exogenous spatial attention can be automatically engaged by a cue presented in the visual periphery. To investigate the effects of exogenous attention, previous studies have generally used highly salient cues that reliably trigger attention. However, the cueing threshold of exogenous attention has been unexamined. We investigated whether the attentional effect varies with cue salience. We examined the magnitude of the attentional effect on apparent contrast [Carrasco, M., Ling, S., & Read, S. (2004). Attention alters appearance. Nature Neuroscience, 7(3), 308–313.] elicited by cues with negative Weber contrast between 6% and 100%. Cue contrast modulated the attentional effect, even at cue contrasts above the level at which observers can perfectly localize the cue; hence, the result is not due to an increase in cue visibility. No attentional effect is observed when the 100% contrast cue is presented after the stimuli, ruling out cue bias or sensory interaction between cues and stimuli as alternative explanations. A second experiment, using the same paradigm with high contrast motion stimuli gave similar results, providing further evidence against a sensory interaction explanation, as the stimuli and task were defined on a visual dimension independent from cue contrast. Although exogenous attention is triggered automatically and involuntarily, the attentional effect is gradual.
PMCID: PMC3684626  PMID: 19393260
Attention; Appearance; Perceived contrast; Perceived speed; Exogenous cue; Threshold; Cue salience
5.  Functional Neural Correlates of Attentional Deficits in Amnestic Mild Cognitive Impairment 
PLoS ONE  2013;8(1):e54035.
Although amnestic mild cognitive impairment (aMCI; often considered a prodromal phase of Alzheimer’s disease, AD) is most recognized by its implications for decline in memory function, research suggests that deficits in attention are present early in aMCI and may be predictive of progression to AD. The present study used functional magnetic resonance imaging to examine differences in the brain during the attention network test between 8 individuals with aMCI and 8 neurologically healthy, demographically matched controls. While there were no significant behavioral differences between groups for the alerting and orienting functions, patients with aMCI showed more activity in neural regions typically associated with the networks subserving these functions (e.g., temporoparietal junction and posterior parietal regions, respectively). More importantly, there were both behavioral (i.e., greater conflict effect) and corresponding neural deficits in executive control (e.g., less activation in the prefrontal and anterior cingulate cortices). Although based on a small number of patients, our findings suggest that deficits of attention, especially the executive control of attention, may significantly contribute to the behavioral and cognitive deficits of aMCI.
PMCID: PMC3543395  PMID: 23326568
6.  Functional deficits of the attentional networks in autism 
Brain and Behavior  2012;2(5):647-660.
Attentional dysfunction is among the most consistent observations of autism spectrum disorders (ASD). However, the neural nature of this deficit in ASD is still unclear. In this study, we aimed to identify the neurobehavioral correlates of attentional dysfunction in ASD. We used the Attention Network Test-Revised and functional magnetic resonance imaging to examine alerting, orienting, and executive control functions, as well as the neural substrates underlying these attentional functions in unmedicated, high-functioning adults with ASD (n = 12) and matched healthy controls (HC, n = 12). Compared with HC, individuals with ASD showed increased error rates in alerting and executive control, accompanied by lower activity in the mid-frontal gyrus and the caudate nucleus for alerting, and by the absence of significant functional activation in the anterior cingulate cortex (ACC) for executive control. In addition, greater behavioral deficiency in executive control in ASD was correlated with less functional activation of the ACC. These findings of behavioral and neural abnormalities in alerting and executive control of attention in ASD may suggest core attentional deficits, which require further investigation.
PMCID: PMC3489817  PMID: 23139910
Alerting; anterior cingulate cortex; attentional networks; autism; executive control
7.  Involvement of the anterior cingulate and frontoinsular cortices in rapid processing of salient facial emotional information 
NeuroImage  2010;54(3):2539-2546.
The anterior cingulate cortex (ACC) and frontoinsular cortex (FI) have been implicated in processing information across a variety of domains, including those related to attention and emotion. However, their role in rapid information processing, for example, as required for timely processing of salient stimuli, is not well understood. Here, we designed an emotional face priming paradigm and employed functional magnetic resonance imaging to elucidate their role in these mechanisms. Target faces with either neutral or fearful emotion were briefly primed by either neutral or fearful faces, or by blank ovals. Activation in the pregenual ACC and the FI, together with other regions, such as the amygdala, were preferentially activated in response to fearful face priming, suggesting that these regions are involved in the rapid processing of salient facial emotional information.
PMCID: PMC3006498  PMID: 20937394
anterior cingulate cortex; emotion; fMRI; frontoinsular cortex; priming

Results 1-7 (7)