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1.  Cognition–Emotion Integration in the Anterior Insular Cortex 
Cerebral Cortex (New York, NY)  2012;23(1):20-27.
Both cognitive and affective processes require mental resources. However, it remains unclear whether these 2 processes work in parallel or in an integrated fashion. In this functional magnetic resonance imaging study, we investigated their interaction using an empathy-for-pain paradigm, with simultaneous manipulation of cognitive demand of the tasks and emotional valence of the stimuli. Eighteen healthy adult participants viewed photographs showing other people's hands and feet in painful or nonpainful situations while performing tasks of low (body part judgment) and high (laterality judgment) cognitive demand. Behavioral data showed increased reaction times and error rates for painful compared with nonpainful stimuli under laterality judgment relative to body part judgment, indicating an interaction between cognitive demand and stimulus valence. Imaging analyses showed activity in bilateral anterior insula (AI) and primary somatosensory cortex (SI), but not posterior insula, for main effects of cognitive demand and stimulus valence. Importantly, cognitive demand and stimulus valence showed a significant interaction in AI, SI, and regions of the frontoparietal network. These results suggest that cognitive and emotional processes at least partially share common brain networks and that AI might serve as a key node in a brain network subserving cognition–emotion integration.
PMCID: PMC3513949  PMID: 22275476
cognition; emotion; empathy; fMRI; insula
2.  Too little, too late or too much, too early? Differential hemodynamics of response inhibition in high and low sensation seekers 
Brain research  2012;1481:1-12.
High sensation seeking is associated with strong approach behaviors and weak avoidance responses. The present study used functional magnetic resonance imaging (fMRI) to further characterize the neurobiological underpinnings of this behavioral profile using a Go/No-go task. Analysis of brain activation associated with response inhibition (No-go) versus response initiation and execution (Go) revealed the commonly reported right lateral prefrontal, insula, cingulate, and supplementary motor area network. However, right lateral activation was associated with greater No-go than Go responses only in low sensation seekers. High sensation seekers showed no differential activation in these regions but a more pronounced Go compared to No-go response in several other regions that are involved in salience detection (insula), motor initiation (anterior cingulate) and attention (inferior parietal cortex). Temporal analysis of the hemodynamic response for Go and No-go conditions revealed that the stronger response to Go than No-go trials in high sensation seekers occurred in in the earliest time window in the right middle frontal gyrus, right mid-cingulate and right precuneus. In contrast, the greater No-go than Go response in low sensation seekers occurred in the later time window in these same regions. These findings indicate that high sensation seekers more strongly attend to or process Go trials and show delayed or minimal inhibitory responses on No-go trials in regions that low sensation seekers use for response inhibition. Failure to engage such regions for response inhibition may underlie some of the risky and impulsive behaviors observed in high sensation seekers.
PMCID: PMC3637656  PMID: 22902769
Functional magnetic resonance imaging; cognitive control; personality
3.  Anterior insular cortex is necessary for empathetic pain perception 
Brain  2012;135(9):2726-2735.
Empathy refers to the ability to perceive and share another person’s affective state. Much neuroimaging evidence suggests that observing others’ suffering and pain elicits activations of the anterior insular and the anterior cingulate cortices associated with subjective empathetic responses in the observer. However, these observations do not provide causal evidence for the respective roles of anterior insular and anterior cingulate cortices in empathetic pain. Therefore, whether these regions are ‘necessary’ for empathetic pain remains unknown. Herein, we examined the perception of others’ pain in patients with anterior insular cortex or anterior cingulate cortex lesions whose locations matched with the anterior insular cortex or anterior cingulate cortex clusters identified by a meta-analysis on neuroimaging studies of empathetic pain perception. Patients with focal anterior insular cortex lesions displayed decreased discrimination accuracy and prolonged reaction time when processing others’ pain explicitly and lacked a typical interference effect of empathetic pain on the performance of a pain-irrelevant task. In contrast, these deficits were not observed in patients with anterior cingulate cortex lesions. These findings reveal that only discrete anterior insular cortex lesions, but not anterior cingulate cortex lesions, result in deficits in explicit and implicit pain perception, supporting a critical role of anterior insular cortex in empathetic pain processing. Our findings have implications for a wide range of neuropsychiatric illnesses characterized by prominent deficits in higher-level social functioning.
PMCID: PMC3437027  PMID: 22961548
anterior cingulate cortex; anterior insular cortex; empathy; meta-analysis; necessity
4.  Sensation Seeking Predicts Brain Responses in the Old-New Task: Converging Multimodal Neuroimaging Evidence 
Novel images and message content enhance visual attention and memory for high sensation seekers, but the neural mechanisms associated with this effect are unclear. To investigate the individual differences in brain responses to new and old (studied) visual stimuli, we utilized Event-related Potentials (ERP) and functional Magnetic Resonance Imaging (fMRI) measures to examine brain reactivity among high and low sensation seekers during a classic old-new memory recognition task. Twenty low and 20 high sensation seekers completed separate, but parallel, ERP and fMRI sessions. For each session, participants initially studied drawings of common images, and then performed an old-new recognition task during scanning. High sensation seekers showed greater ERP responses to new objects at the frontal N2 ERP component, compared to low sensation seekers. The ERP Novelty-N2 responses were correlated with fMRI responses in the orbitofrontal gyrus. Sensation seeking status also modulated the FN400 ERP component indexing familiarity and conceptual learning, along with fMRI responses in the caudate nucleus, which correlated with FN400 activity. No group differences were found in the late ERP positive components indexing classic old-new amplitude effects. Our combined ERP & fMRI results suggest that sensation-seeking personality affects the early brain responses to visual processing, but not the later stage of memory recognition.
PMCID: PMC3367102  PMID: 22484516
novelty seeking personality; old-new effect; recognition memory; evoked potentials; brain imaging; ERP; fMRI
5.  Parental substance abuse and function of the motivation and behavioral inhibition systems in drug-naïve youth 
Psychiatry Research  2012;201(2):128-135.
PMCID: PMC3335432  PMID: 22386967
fMRI; motivation-reward; behavioral inhibition; risk for substance abuse; ADHD
6.  Effects of motivation on reward and attentional networks: an fMRI study 
Brain and Behavior  2012;2(6):741-753.
Existing evidence suggests that reward and attentional networks function in concert and that activation in one system influences the other in a reciprocal fashion; however, the nature of these influences remains poorly understood. We therefore developed a three-component task to assess the interaction effects of reward anticipation and conflict resolution on the behavioral performance and the activation of brain reward and attentional systems. Sixteen healthy adult volunteers aged 21–45 years were scanned with functional magnetic resonance imaging (fMRI) while performing the task. A two-way repeated measures analysis of variance (ANOVA) with cue (reward vs. non-reward) and target (congruent vs. incongruent) as within-subjects factors was used to test for main and interaction effects. Neural responses to anticipation, conflict, and reward outcomes were tested. Behaviorally there were main effects of both reward cue and target congruency on reaction time. Neuroimaging results showed that reward anticipation and expected reward outcomes activated components of the attentional networks, including the inferior parietal and occipital cortices, whereas surprising non-rewards activated the frontoinsular cortex bilaterally and deactivated the ventral striatum. In turn, conflict activated a broad network associated with cognitive control and motor functions. Interaction effects showed decreased activity in the thalamus, anterior cingulated gyrus, and middle frontal gyrus bilaterally when difficult conflict trials (e.g., incongruent targets) were preceded by reward cues; in contrast, the ventral striatum and orbitofrontal cortex showed greater activation during congruent targets preceded by reward cues. These results suggest that reward anticipation is associated with lower activation in attentional networks, possibly due to increased processing efficiency, whereas more difficult, conflict trials are associated with lower activity in regions of the reward system, possibly because such trials are experienced as less rewarding.
PMCID: PMC3500461  PMID: 23170237
Attention; brain reward system; fMRI; motivation; neuroimaging; neuroscience
7.  Variability of glomerular filtration rate estimation equations in elderly Chinese patients with chronic kidney disease 
Chronic kidney disease (CKD) is recognized worldwide as a public health problem, and its prevalence increases as the population ages. However, the applicability of formulas for estimating the glomerular filtration rate (GFR) based on serum creatinine (SC) levels in elderly Chinese patients with CKD is limited.
Materials and methods
Based on values obtained with the technetium-99m diethylenetriaminepentaacetic acid (99mTc-DTPA) renal dynamic imaging method, 319 elderly Chinese patients with CKD were enrolled in this study. Serum creatinine was determined by the enzymatic method. The GFR was estimated using the Cockroft–Gault (CG) equation, the Modification of Diet in Renal Disease (MDRD) equations, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, the Jelliffe-1973 equation, and the Hull equation.
The median of difference ranged from −0.3–4.3 mL/min/1.73 m2. The interquartile range (IQR) of differences ranged from 13.9–17.6 mL/min/1.73 m2. Accuracy with a deviation less than 15% ranged from 27.6%–32.9%. Accuracy with a deviation less than 30% ranged from 53.6%–57.7%. Accuracy with a deviation less than 50% ranged from 74.9%–81.5%. None of the equations had accuracy up to the 70% level with a deviation less than 30% from the standard glomerular filtration rate (sGFR). Bland–Altman analysis demonstrated that the mean difference ranged from −3.0–2.4 mL/min/1.73 m2. However, the agreement limits of all the equations, except the CG equation, exceeded the prior acceptable tolerances defined as 60 mL/min/1.73 m2. When the overall performance and accuracy were compared in different stages of CKD, GFR estimated using the CG equation showed promising results.
Our study indicated that none of these equations were suitable for estimating GFR in the elderly Chinese population investigated. At present, based on overall performance, as well as performance in different CKD stages, the CG equation may be the most accurate for estimating GFR in elderly Chinese patients with CKD.
PMCID: PMC3474145  PMID: 23091374
elderly; equation; glomerular filtration rate; serum creatinine; Chinese
8.  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
9.  Cannabis-Dependence Risk Relates to Synergism between Neuroticism and Proenkephalin SNPs Associated with Amygdala Gene Expression: Case-Control Study 
PLoS ONE  2012;7(6):e39243.
Many young people experiment with cannabis, yet only a subgroup progress to dependence suggesting individual differences that could relate to factors such as genetics and behavioral traits. Dopamine receptor D2 (DRD2) and proenkephalin (PENK) genes have been implicated in animal studies with cannabis exposure. Whether polymorphisms of these genes are associated with cannabis dependence and related behavioral traits is unknown.
Methodology/Principal Findings
Healthy young adults (18–27 years) with cannabis dependence and without a dependence diagnosis were studied (N = 50/group) in relation to a priori-determined single nucleotide polymorphisms (SNPs) of the DRD2 and PENK genes. Negative affect, Impulsive Risk Taking and Neuroticism-Anxiety temperamental traits, positive and negative reward-learning performance and stop-signal reaction times were examined. The findings replicated the known association between the rs6277 DRD2 SNP and decisions associated with negative reinforcement outcomes. Moreover, PENK variants (rs2576573 and rs2609997) significantly related to Neuroticism and cannabis dependence. Cigarette smoking is common in cannabis users, but it was not associated to PENK SNPs as also validated in another cohort (N = 247 smokers, N = 312 non-smokers). Neuroticism mediated (15.3%–19.5%) the genetic risk to cannabis dependence and interacted with risk SNPs, resulting in a 9-fold increase risk for cannabis dependence. Molecular characterization of the postmortem human brain in a different population revealed an association between PENK SNPs and PENK mRNA expression in the central amygdala nucleus emphasizing the functional relevance of the SNPs in a brain region strongly linked to negative affect.
Overall, the findings suggest an important role for Neuroticism as an endophenotype linking PENK polymorphisms to cannabis-dependence vulnerability synergistically amplifying the apparent genetic risk.
PMCID: PMC3382183  PMID: 22745721
10.  Downregulation of Chloroplast RPS1 Negatively Modulates Nuclear Heat-Responsive Expression of HsfA2 and Its Target Genes in Arabidopsis 
PLoS Genetics  2012;8(5):e1002669.
Heat stress commonly leads to inhibition of photosynthesis in higher plants. The transcriptional induction of heat stress-responsive genes represents the first line of inducible defense against imbalances in cellular homeostasis. Although heat stress transcription factor HsfA2 and its downstream target genes are well studied, the regulatory mechanisms by which HsfA2 is activated in response to heat stress remain elusive. Here, we show that chloroplast ribosomal protein S1 (RPS1) is a heat-responsive protein and functions in protein biosynthesis in chloroplast. Knockdown of RPS1 expression in the rps1 mutant nearly eliminates the heat stress-activated expression of HsfA2 and its target genes, leading to a considerable loss of heat tolerance. We further confirm the relationship existed between the downregulation of RPS1 expression and the loss of heat tolerance by generating RNA interference-transgenic lines of RPS1. Consistent with the notion that the inhibited activation of HsfA2 in response to heat stress in the rps1 mutant causes heat-susceptibility, we further demonstrate that overexpression of HsfA2 with a viral promoter leads to constitutive expressions of its target genes in the rps1 mutant, which is sufficient to reestablish lost heat tolerance and recovers heat-susceptible thylakoid stability to wild-type levels. Our findings reveal a heat-responsive retrograde pathway in which chloroplast translation capacity is a critical factor in heat-responsive activation of HsfA2 and its target genes required for cellular homeostasis under heat stress. Thus, RPS1 is an essential yet previously unknown determinant involved in retrograde activation of heat stress responses in higher plants.
Author Summary
As a consequence of global warming, increasing temperature is a serious threat to crop production worldwide and may influence the objectives of breeding programs. As a universal cellular response to a shift up in temperature, the heat stress response represents the first line of inducible defense against imbalances in cellular homeostasis in the prokaryotic and eukaryotic kingdoms. Given that components of the photosynthetic apparatus housed in the chloroplast are the primary susceptible targets of thermal damage in plants, the chloroplasts were proposed as sensors to a shift up in temperature. However, the mechanism by which chloroplasts regulate the expression of nuclear heat stress–responsive gene expression according to the functional state of chloroplasts under heat stress remains unknown. In this study, we have identified chloroplast ribosomal protein S1 (RPS1) as a heat-responsive protein through proteomic screening of heat-responsive proteins. We have established a previously unrecognized molecular connection between the downregulation of RPS1 expression in chloroplast and the activation of HsfA2-dependent heat-responsive genes in nucleus, which is required for heat tolerance in higher plants. Our data provide new insights into the mechanisms whereby plant cells modulate nuclear gene expression to keep accordance with the current status of chloroplasts in response to heat stress.
PMCID: PMC3342936  PMID: 22570631
11.  Methamphetamine Increases LPS-Mediated Expression of IL-8, TNF-α and IL-1β in Human Macrophages through Common Signaling Pathways 
PLoS ONE  2012;7(3):e33822.
The use of methamphetamine (MA) has increased in recent years, and is a major health concern throughout the world. The use of MA has been associated with an increased risk of acquiring HIV-1, along with an increased probability of the acquisition of various sexually transmitted infections. In order to determine the potential effects of MA exposure in the context of an infectious agent, U937 macrophages were exposed to various combinations of MA and bacterial lipopolysaccharide (LPS). Treatment with MA alone caused significant increases in the levels of TNF-α, while treatment with both MA and LPS resulted in significant increases in TNF-α, IL-1β and the chemokine IL-8. The increases in cytokine or chemokine levels seen when cells were treated with both LPS and MA were generally greater than those increases observed when cells were treated with only LPS. Treatment with chemical inhibitors demonstrated that the signal transduction pathways including NF-kB, MAPK, and PI3-Akt were involved in mediating the increased inflammatory response. As discussed in the paper, these pathways appear to be utilized by both MA and LPS, in the induction of these inflammatory mediators. Since these pathways are involved in the induction of inflammation in response to other pathogens, this suggests that MA-exacerbated inflammation may be a common feature of infectious disease in MA abusers.
PMCID: PMC3315580  PMID: 22479453
12.  Bis[(1S,1′S)-1,1′-(4-amino-4H-1,2,4-triazole-3,5-di­yl)diethanol-κN 1]bis­(nitrato-κO)zinc 
In the title homochiral mononuclear compound, [Zn(NO3)2(C6H12N4O2)2], the ZnII atom is located on a twofold rotation axis and coordinated by two N atoms from two ligands and two O atoms from two NO3 − anions, adopting a distorted tetra­hedral coordination geometry. The compound is enanti­omerically pure and corresponds to the S diastereoisomer, with the optical activity originating from the chiral ligand. In the crystal, mol­ecules are connected into three-dimensional supra­molecular networks through O—H⋯O, O—H⋯N and N—H⋯O hydrogen bonds.
PMCID: PMC3274914  PMID: 22346861

Results 1-12 (12)