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1.  Hippocampal neuronal cyclooxygenase-2 downstream signaling imbalance in a rat model of chronic aluminium gluconate administration 
Background
Acute and chronic brain damages including neurodegenerative diseases are a group of neuroinflammation-associated diseases characterized by cognitive function defect and progressive neuron loss. The pathophysiological procession of brain damages involves the overexpression of cyclooxygenase (COX)-2. Owing to the limited benefit to chronic brain damage and the late adverse effect of COX-2 inhibitors, the COX downstream signaling pathway has become a focus in neurological research. In order to explore the mechanism of aluminum neurotoxicity and the importance of COX2 downstream signaling pathways to chronic brain damage, the present study was designed to simultaneously observe the prostaglandin (PG) contents, and the expressions of PG synthases and PG receptors of hippocampus in a rat model induced by chronic administration of aluminium gluconate.
Methods
A rat model of chronic brain damage was established by chronic intragastric administration of aluminium gluconate (Al3+ 200 mg/kg per day, 5d a week for 20 weeks). PG contents, the expressions of PG synthases, and the expressions of PG receptors in rats were measured by ELISA, RT-PCR and Western blotting, respectively.
Results
Chronic aluminium gluconate administration resulted in hippocampal neuron injury and learning and memory disorders in rats. Aluminium gluconate administration also resulted in increased levels of PGE2, PGD2, TXA2, PGI2, and PGF2α in rat hippocampus. The DP1, EP2, IP, mPGES-1, EP4, PGIS and TXAS mRNA expressions, and the DP1, EP2 and IP protein expressions significantly increased in the Al-treated hippocampus, while the EP3 and FP mRNA and protein expressions and the TP mRNA expression decreased.
Conclusions
The PGS/PGs/PG receptors signaling pathway in chronic aluminium gluconate-overloaded rat hippocampus is disturbed, which may be involved in the mechanism of aluminium neurotoxicity.
doi:10.1186/s12993-015-0054-z
PMCID: PMC4336726
Aluminium gluconate; Neurotoxicity; Cyclooxygenase; Prostaglandins; Prostaglandin synthases; Prostaglandin receptors
2.  Neurochemical, structural and neurobehavioral evidence of neuronal protection by whey proteins in diabetic albino mice 
Background
Diabetes Mellitus (DM) is associated with pathological changes in the central nervous system (CNS) and alterations in oxidative stress. The aim of this study was to determine whether dietary supplement with whey protein (WP) could improve neurobehavior, oxidative stress and neuronal structure in the CNS.
Methods
Animals were distributed in three groups, a control group (N), a diabetic mellitus group (DM) and a DM group orally supplemented with WP (WP).
Results
The DM group of animals receiving WP had reduced blood glucose, significantly decreased free radical Diphenyl-picrylhydrazyl (DPPH) and lower lipid peroxidation in brain tissue. The WP group of animals showed improvement in balancing, coordination and fore-limb strength, oxidative stress and neuronal structure.
Conclusion
The results of this study show that dietary supplementation with WP reduced oxidative stress, protected CNS neurons and improved the neurobehavior of diabetic mice.
doi:10.1186/s12993-015-0053-0
PMCID: PMC4331294
Whey protein; Diabetes; Oxidative stress
3.  Beraprost sodium protects against chronic brain injury in aluminum-overload rats 
Background
Aluminum overload can cause severe brain injury and neurodegeneration. Previous studies suggest that prostacyclin synthase (PGIS) expression and prostacyclin receptor (IP) activation are beneficial for treatment of acute traumatic and ischemic brain injury. However, the potential value of PGIS/IP signaling pathway to chronic brain injury is still unclear. In this study, we investigated the change of PGIS/IP signaling pathway and the effect of beraprost sodium (BPS) on chronic brain injury in chronic aluminum-overload rats.
Methods
Rat model of chronic cerebral injury was established by chronic intragastric administration of aluminum gluconate(Al3+ 200 mg/kg per day,5d a week for 20 weeks). The methods of ELISA, qRT-PCR and Western blotting were used to detect the PGI2 level and the PGIS and IP mRNA and protein levels in hippocampi of chronic aluminum-overload rats, respectively. Rat hippocampal superoxide dismutase (SOD) activity and malondialdehyde (MDA) content also were measured. The effects of BPS (6, 12 and 24 μg⋅kg-1) on brain injury in chronic aluminum-overload rats were evaluated.
Results
Compared with the control group, PGIS mRNA expression, PGI2 level, and the IP mRNA and protein expressions significantly increased in hippocampi of chronic aluminum-overload rats. Administration of BPS significantly improved spatial learning and memory function impairment and hippocampal neuron injury induced by chronic aluminum overload in rats. Meanwhile, administration of BPS resulted in a decrease of PGI2 level and downregulation of PGIS and IP expressions in a dose-dependent manner. Aluminum overload also caused a decrease of SOD activity and an increase of MDA content. Administration of BPS significantly blunted the decrease of SOD activity and the increase of MDA content induced by aluminum overload in rats.
Conclusions
BPS has a significant neuroprotective effect on chronic brain injury induced by aluminum overload in rats. Remodeling the balance of PGIS/IP signaling pathway and inhibition of oxidative stress involve in the neuroprotective mechanism of BPS in aluminum-overload rats. The PGIS/IP signaling pathway is a potential therapeutic strategy for chronic brain injury patients.
doi:10.1186/s12993-014-0051-7
PMCID: PMC4326490
Chronic brain injury; Beraprost sodium; PGI2 level; PGIS; IP receptor
4.  Reduced levels of plasma polyunsaturated fatty acids and serum carnitine in autistic children: relation to gastrointestinal manifestations 
Background
Gastrointestinal (GI) manifestations are common in autistic children. Polyunsaturated fatty acids (PUFAs) and carnitine are anti-inflammatory molecules and their deficiency may result in GI inflammation. The relationship between the increased frequency of GI manifestations and reduced levels of PUFAs and carnitine was not previously investigated in autistic patients. This study was the first to investigate plasma levels of PUFAs and serum carnitine in relation to GI manifestations in autistic children.
Methods
Plasma levels of PUFAs (including linoleic, alphalinolenic, arachidonic “AA” and docosahexaenoic “DHA” acids) and serum carnitine were measured in 100 autistic children and 100 healthy-matched children.
Results
Reduced levels of serum carnitine and plasma DHA, AA, linolenic and linoleic acids were found in 66%, 62%, 60%, 43% and 38%, respectively of autistic children. On the other hand, 54% of autistic patients had elevated ω6/ω3 ratio. Autistic patients with GI manifestations (48%) had significantly decreased levels of serum carnitine and plasma DHA than patients without such manifestations. In addition, autistic patients with GI manifestations had significantly increased percentage of reduced serum carnitine (91.7%) and plasma DHA levels (87.5%) than patients without such manifestations (42.3% and 38.5%, respectively), (P < 0.001 and P < 0.001%, respectively).
Conclusions
Reduced levels of plasma DHA and serum carnitine levels may be associated with the GI problems in some autistic patients. However, this is an initial report, studies are recommended to invesigate whether reduced levels of carnitine and DHA are a mere association or have a pathogenic role in GI problems in autistic patients.
doi:10.1186/s12993-014-0048-2
PMCID: PMC4332725
Autism; Brain energy; Carnitine; Docosahexaenoic acid; Gastrointestinal manifestations; Polyunsaturated fatty acids
5.  Tat-induced histopathological alterations mediate hippocampus-associated behavioural impairments in rats 
Background
HIV-1 is a global catastrophe, and is exceedingly prevalent in Sub-Saharan Africa. HIV-associated neurocognitive disorder is characterized by symptoms such as motor impairments, a decline in cognition, and behavioural irregularities. The aim of this study was to provide insight into the fundamental behavioural and histopathological mechanisms underlying the development and progression of HIV-1 neuropathology.
Methods
Using stereotaxic techniques, Tat protein Clade B (1 μg/μl, 10 μl) was injected bilaterally into the dorsal hippocampus of male Sprague–Dawley rats. The Morris water maze (MWM) and novel object recognition test (NORT) were used to assess spatial learning and recognition memory, respectively. Haematoxylin and eosin staining was used to identify the histopathological changes.
Results
A highly significant increase in latency to reach the hidden platform in the MWM implied that noteworthy hippocampal damage had occurred. Severe behavioural deficits were also observed in the NORT where the Tat-injected group showed a greater preference for a familiar object over a novel one. This damage was confirmed by the histopathological changes (increased astrogliosis, cells becoming eosinophilic and a significant reduction in the pyramidal cell layer) observed in the hippocampus. Additionally, increases in the hippocampal mass and protein were observed, consistent with the structural alterations.
Conclusion
This study highlights the relationship between hippocampal-associated behavioural changes and histologic alterations following stereotaxic intra-hippocampal administration of Tat protein in rats. The implications of this study may positively impact the fields of immunology and neuroscience by encouraging future researchers to consider novel strategies to understand the complexities of the pathogenesis of HIV-associated neurocognitive disorder.
doi:10.1186/s12993-014-0047-3
PMCID: PMC4333156
Tat protein Clade B; Morris water maze; Novel object recognition test; Histopathology; Hippocampus
6.  Patterns of linguistic and numerical performance in aphasia 
Background
Empirical research on the relationship between linguistic and numerical processing revealed inconsistent results for different levels of cognitive processing (e.g., lexical, semantic) as well as different stimulus materials (e.g., Arabic digits, number words, letters, non-number words). Information of dissociation patterns in aphasic patients was used in order to investigate the dissociability of linguistic and numerical processes. The aim of the present prospective study was a comprehensive, specific, and systematic investigation of relationships between linguistic and numerical processing, considering the impact of asemantic vs. semantic processing and the type of material employed (numbers compared to letters vs. words).
Methods
A sample of aphasic patients (n = 60) was assessed with a battery of linguistic and numerical tasks directly comparable for their cognitive processing levels (e.g., perceptual, morpho-lexical, semantic).
Results and conclusions
Mean performance differences and frequencies of (complementary) dissociations in individual patients revealed the most prominent numerical advantage for asemantic tasks when comparing the processing of numbers vs. letters, whereas the least numerical advantage was found for semantic tasks when comparing the processing of numbers vs. words. Different patient subgroups showing differential dissociation patterns were further analysed and discussed. A comprehensive model of linguistic and numerical processing should take these findings into account.
Electronic supplementary material
The online version of this article (doi:10.1186/s12993-014-0049-1) contains supplementary material, which is available to authorized users.
doi:10.1186/s12993-014-0049-1
PMCID: PMC4331419  PMID: 25648216
Numerical cognition; Aphasia; Double dissociations
7.  Decoding the processing of lying using functional connectivity MRI 
Background
Previous functional MRI (fMRI) studies have demonstrated group differences in brain activity between deceptive and honest responses. The functional connectivity network related to lie-telling remains largely uncharacterized.
Methods
In this study, we designed a lie-telling experiment that emphasized strategy devising. Thirty-two subjects underwent fMRI while responding to questions in a truthful, inverse, or deceitful manner. For each subject, whole-brain functional connectivity networks were constructed from correlations among brain regions for the lie-telling and truth-telling conditions. Then, a multivariate pattern analysis approach was used to distinguish lie-telling from truth-telling based on the functional connectivity networks.
Results
The classification results demonstrated that lie-telling could be differentiated from truth-telling with an accuracy of 82.81% (85.94% for lie-telling, 79.69% for truth-telling). The connectivities related to the fronto-parietal networks, cerebellum and cingulo-opercular networks are most discriminating, implying crucial roles for these three networks in the processing of deception.
Conclusions
The current study may shed new light on the neural pattern of deception from a functional integration viewpoint.
Electronic supplementary material
The online version of this article (doi:10.1186/s12993-014-0046-4) contains supplementary material, which is available to authorized users.
doi:10.1186/s12993-014-0046-4
PMCID: PMC4316800  PMID: 25595193
fMRI; Deception; Multivariate pattern analysis; Functional connectivity
8.  Post-adolescent developmental changes in cortical complexity 
Background
Post-adolescence is known to be a period of general maturation and development in the human brain. In brain imaging, volumetric and morphologic cortical grey-matter changes can easily be assessed, but the analysis of cortical complexity seems to have been broadly neglected for this age interval.
Methods
Magnetic resonance imaging (MRI) was used to acquire structural brain images. The study involved 17 adolescents (mean age 14.1 ± 0.27, 11 girls) who were compared with 14 young adults (mean age 24.24 ± 2.76, 7 women) for measures of brain complexity (fractal dimension - FD), grey matter (GM) volume and surface-area of cortical ribbon. FD was calculated using box-counting and Minkowski-Bouligand methods; FD and GM volume were measured for the whole brain, each hemisphere and lobes: frontal, occipital, parietal and temporal.
Results
The results show that the adults have a lower cortical complexity than the adolescents, which was significant for whole brain, left and right hemisphere, frontal and parietal lobes for both genders; and only for males in left temporal lobe. The GM volume was smaller in men than in boys for almost all measurements, and smaller in women than in girls just for right parietal lobe. A significant Pearson correlation was found between FD and GM volume for whole brain and each hemisphere in both genders. The decrease of the GM surface-area was significant in post-adolescence for males, not for females.
Conclusions
During post-adolescence there are common changes in cortical complexity in the same regions for both genders, but there are also gender specific changes in some cortical areas. The sex differences from different cortical measurements (FD, GM volume and surface-area of cortical ribbon) could suggest a maturation delay in specific brain regions for each gender in relation to the other and might be explained through the functional role of the corresponding regions reflected in gender difference of developed abilities.
doi:10.1186/1744-9081-10-44
PMCID: PMC4289042  PMID: 25431294
Grey matter; Fractal dimension; Development; Dimorphism; Magnetic resonance imaging
9.  Time course change of COX2-PGI2/TXA2 following global cerebral ischemia reperfusion injury in rat hippocampus 
Background
Neuroinflammation plays pivotal roles in the progression of cerebral ischemia injury. Prostaglandins (PGs) as the major inflammatory mediators in the brain participate in the pathophysiological processes of cerebral ischemia injury. Cyclooxygenase-2 (COX2) is the rate-limiting enzyme of PGs, and thus it is necessary to characterize of the expression patterns of COX2 and its downstream products at the same time in a cerebral ischemia/reperfusion (I/R) model.
Methods
The levels of prostacyclin (PGI2) and thromboxane (TXA2) and the expression of COX2 were detected in the rat hippocampus at different time points after reperfusion (30 min, 2 h, 6 h, 24 h, 48 h, 7 d, and 15 d).
Results
The COX2 mRNA and protein expressions in hippocampus both remarkably increased at 30 min, and peaked at 7 d after global cerebral I/R compared with the sham-operated group. The level of PGI2 significantly increased at 2 h after reperfusion, with a peak at 48 h, but was still significantly higher than the sham-operated animals at 15 d. TXA2 level decreased at 30 min and 2 h after reperfusion, but significantly increased at 6 h and peaked at 48 h. PGI2/TXA2 ratio increased at 30 min after reperfusion, and peaked at 48 h compared with the sham-operated animals.
Conclusions
I/R injury significantly increased the COX2 expression, PGI2 and TXA2 levels, and the PGI2/TXA2 ratio in rat hippocampus in a time-dependent manner. As a consequence, the increased PGI2 level and PGI2/TXA2 ratio may represent a physiological mechanism to protect the brain against the neuronal damage produced by I/R injury.
doi:10.1186/1744-9081-10-42
PMCID: PMC4240876  PMID: 25388440
Global cerebral ischemia reperfusion; PGI2; TXA2; COX2; PGI2/TXA2; Neuroinflammation
10.  A matter of timing: harm reduction in learned helplessness 
Background
Learned helplessness has excellent validity as an animal model for depression, but problems in reproducibility limit its use and the high degree of stress involved in the paradigm raises ethical concerns. We therefore aimed to identify which and how many trials of the learned helplessness paradigm are necessary to distinguish between helpless and non-helpless rats.
Findings
A trial-by-trial reanalysis of tests from 163 rats with congenital learned helplessness or congenital non-learned helplessness and comparison of 82 rats exposed to inescapable shock with 38 shock-controls revealed that neither the first test trials, when rats showed unspecific hyperlocomotion, nor trials of the last third of the test, when almost all animals responded quickly to the stressor, contributed to sensitivity and specificity of the test. Considering only trials 3–10 improved the classification of helpless and non-helpless rats.
Conclusions
The refined analysis allows abbreviation of the test for learned helplessness from 15 trials to 10 trials thereby reducing pain and stress of the experimental animals without losing statistical power.
doi:10.1186/1744-9081-10-41
PMCID: PMC4232717  PMID: 25365925
Learned helplessness; Reliability; Refinement; Harm reduction; Latency measures; ROC-curves
11.  The formation of source memory under distraction 
Background
It is vital to select and process relevant information while restraining irrelevant information for successful retrieval. When multiple streams of information are concurrently present, the ability to overcome distraction is very crucial for processing relevant information. Despite its significance, the neural mechanism of successful memory formation under distraction remains unclear, especially with memory for associations. The present fMRI study investigated the effect of distraction due to irrelevant stimuli in source memory.
Methods
In the MR scanner, participants studied an item and perceptual context with no distractor, a letter-distractor, or a word-distractor. Following the study phase, a source recognition test was administered in which participants were instructed to judge the study status of the test items and context of studied items. Participants’ encoding activity was back-sorted by later source recognition to find the influence of distractors in subsequent memory effects.
Results
Source memory with distractors recruited greater encoding activity in the left dorsolateral prefrontal cortex, and the bilateral inferior temporal gyrus/fusiform cortex, along with the left posterior hippocampus. However, enhanced activity in the left anterior ventrolateral prefrontal cortex and the left parahippocampal cortex predicted successful source memory regardless of the presence of a distractor.
Conclusions
These findings of subsequent memory effects suggest that strong binding of the item-context associations, as well as resistance to interference, may have greater premium in the formation of successful source memory of pictures under distraction. Further, attentional selection to the relevant target seems to play a major role in contextual binding under distraction by enhancing the viability of memory representations from interference effects of distractors.
Electronic supplementary material
The online version of this article (doi:10.1186/1744-9081-10-40) contains supplementary material, which is available to authorized users.
doi:10.1186/1744-9081-10-40
PMCID: PMC4218999  PMID: 25344289
Source memory; Distraction; fMRI; Hippocampus; Encoding
12.  Colour vision in ADHD: Part 1 - Testing the retinal dopaminergic hypothesis 
Objectives
To test the retinal dopaminergic hypothesis, which posits deficient blue color perception in ADHD, resulting from hypofunctioning CNS and retinal dopamine, to which blue cones are exquisitely sensitive. Also, purported sex differences in red color perception were explored.
Methods
30 young adults diagnosed with ADHD and 30 healthy young adults, matched on age and gender, performed a psychophysical task to measure blue and red color saturation and contrast discrimination ability. Visual function measures, such as the Visual Activities Questionnaire (VAQ) and Farnsworth-Munsell 100 hue test (FMT), were also administered.
Results
Females with ADHD were less accurate in discriminating blue and red color saturation relative to controls but did not differ in contrast sensitivity. Female control participants were better at discriminating red saturation than males, but no sex difference was present within the ADHD group.
Conclusion
Poorer discrimination of red as well as blue color saturation in the female ADHD group may be partly attributable to a hypo-dopaminergic state in the retina, given that color perception (blue-yellow and red-green) is based on input from S-cones (short wavelength cone system) early in the visual pathway. The origin of female superiority in red perception may be rooted in sex-specific functional specialization in hunter-gather societies. The absence of this sexual dimorphism for red colour perception in ADHD females warrants further investigation.
Electronic supplementary material
The online version of this article (doi:10.1186/1744-9081-10-38) contains supplementary material, which is available to authorized users.
doi:10.1186/1744-9081-10-38
PMCID: PMC4219036  PMID: 25344625
ADHD; Color saturation; Contrast sensitivity; Sex difference
13.  Color vision in ADHD: Part 2 - Does Attention influence Color Perception? 
Background
To investigate the impact of exogenous covert attention on chromatic (blue and red) and achromatic visual perception in adults with and without Attention Deficit Hyperactivity Disorder (ADHD). Exogenous covert attention, which is a transient, automatic, stimulus-driven form of attention, is a key mechanism for selecting relevant information in visual arrays.
Methods
30 adults diagnosed with ADHD and 30 healthy adults, matched on age and gender, performed a psychophysical task designed to measure the effects of exogenous covert attention on perceived color saturation (blue, red) and contrast sensitivity.
Results
The effects of exogenous covert attention on perceived blue and red saturation levels and contrast sensitivity were similar in both groups, with no differences between males and females. Specifically, exogenous covert attention enhanced the perception of blue saturation and contrast sensitivity, but it had no effect on the perception of red saturation.
Conclusion
The findings suggest that exogenous covert attention is intact in adults with ADHD and does not account for the observed impairments in the perception of chromatic (blue and red) saturation.
Electronic supplementary material
The online version of this article (doi:10.1186/1744-9081-10-39) contains supplementary material, which is available to authorized users.
doi:10.1186/1744-9081-10-39
PMCID: PMC4282194  PMID: 25344205
ADHD; Color saturation; Contrast sensitivity; Exogenous covert attention
14.  Assessment of in vivo microstructure alterations in gray matter using DKI in internet gaming addiction 
Background
The aim of the current study was to investigate the utility of diffusional kurtosis imaging (DKI) in the detection of gray matter (GM) alterations in people suffering from Internet Gaming Addiction (IGA).
Methods
DKI was applied to 18 subjects with IGA and to 21 healthy controls (HC). Whole-brain voxel-based analyses were performed with the following derived parameters: mean kurtosis metrics (MK), radial kurtosis (K⊥), and axial kurtosis (K//). A significance threshold was set at P <0.05, AlphaSim corrected. Pearson’s correlation was performed to investigate the correlations between the Chen Internet Addiction Scale (CIAS) and the DKI-derived metrics of regions that differed between groups. Additionally, we used voxel-based morphometry (VBM) to detect GM-volume differences between the two groups.
Results
Compared with the HC group, the IGA group demonstrated diffusional kurtosis parameters that were significantly less in GM of the right anterolateral cerebellum, right inferior and superior temporal gyri, right supplementary motor area, middle occipital gyrus, right precuneus, postcentral gyrus, right inferior frontal gyrus, left lateral lingual gyrus, left paracentral lobule, left anterior cingulate cortex, and median cingulate cortex. The bilateral fusiform gyrus, insula, posterior cingulate cortex (PCC), and thalamus also exhibited less diffusional kurtosis in the IGA group. MK in the left PCC and K⊥ in the right PCC were positively correlated with CIAS scores. VBM showed that IGA subjects had higher GM volume in the right inferior and middle temporal gyri, and right parahippocampal gyrus, and lower GM volume in the left precentral gyrus.
Conclusions
The lower diffusional kurtosis parameters in IGA suggest multiple differences in brain microstructure, which may contribute to the underlying pathophysiology of IGA. DKI may provide sensitive imaging biomarkers for assessing IGA severity.
doi:10.1186/1744-9081-10-37
PMCID: PMC4282196  PMID: 25344114
Internet gaming addiction; Diffusional kurtosis imaging; Gray matter; Posterior cingulate cortex
15.  Right and left amygdalae activation in patients with major depression receiving antidepressant treatment, as revealed by fMRI 
Background
A differential contribution of the right and left amygdalae to affective information processing has been proposed. However, the direction of this lateralization has not been confirmed. In this study, we used a pre- and post-treatment (escitalopram) design to analyze the relative differences between neural activity in the right and left amygdalae during exposure to emotional stimuli in currently depressed patients. To the best of our knowledge, this study is to compare neural activity between the left and right amygdalae in people with depression. Our findings could lead to the development of parameters or biomarkers for depressive symptoms and treatment response.
Methods
We used a pre–post-test design without a control group. Twenty currently depressed participants underwent an emotion processing task during fMRI. These participants were then treated with an antidepressant for 6 weeks. We used amygdala region-of-interest analysis to evaluate the hemodynamic response during exposure to colored emotional pictures.
Results
In total, thirteen of the 20 participants were placed into a separate group based on degree of response to antidepressants. The partial response group had an averaged HDRS score of 10.75 ± 2.25 and an averaged DBOLDLR signal of 189.18 ± 140.23 (m1 = 8), and the remitted group had an averaged HDRS score of 4.80 ± 1.64 and an averaged DBOLDLR signal of 421.26 ± 109.19 (m2 = 5). Each individual had lateralized amygdala activity, and the direction of asymmetry persisted following treatment. Amygdala responses to four types of emotional stimuli did not significantly change (p > 0.05) with treatment in either the right or the left amygdala. However, the difference in neural activity between the right and left amygdalae was greater after treatment, and the variation in neural activity was larger in the left amygdala.
Conclusions
We found that the response between the right and left amygdala did not differ in terms of time series, although activity increased after pharmaceutical treatment for each emotion tested. In the future, changes in BOLD signals as revealed by fMRI might be useful in evaluating the clinical manifestation of major depression.
doi:10.1186/1744-9081-10-36
PMCID: PMC4282198  PMID: 25298173
Amygdala; DBOLDLR signal; Emotion; Major Depression; Antidepressants
16.  Fat-mass and obesity-associated gene polymorphisms and weight gain after risperidone treatment in first episode schizophrenia 
Background
Obesity induced by antipsychotics severely increases the risk of many diseases and significantly reduces quality of life. Genome Wide Association Studies has identified fat-mass and obesity-associated (FTO) gene associated with obesity. The relationship between the FTO gene and drug-induced obesity is unclear.
Method
Two hundred and fifty drug naïve, Chinese Han patients with first-episode schizophrenia were enrolled in the study, and genotyped for four single nucleotide polymorphisms (SNPs rs9939609, rs8050136, rs1421085 and rs9930506) by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing. Body weight and body mass index (BMI) were measured at baseline and six months after risperidone treatment.
Results
At baseline, body weight and BMI of TT homozygotes were lower than those of A allele carriers in rs9939609; body weight of AA homozygotes was higher than those of G allele carriers in rs9930506 (p’s < 0.05). After 6 months of risperidone treatment, body weight and BMI of TT homozygotes were lower than those of A allele carriers in rs9939609 (p’s <0.01); body weight and BMI of CC homozygotes were lower than those of A allele carriers in rs8050136 (p’s < 0.05); body weight of AA homozygotes was higher than those of G allele carriers in rs9930506 (p’s < 0.05). After controlling for age, gender, age of illness onset, disease duration, weight at baseline and education, weight gain of TT homozygotes at 6 months remained to be lower than those of A allele carriers in rs9939609 (p < 0.01); weight gain of CC homozygotes at 6 months was lower than those of A allele carriers in rs8050136 (p = 0.01). Stepwise multiple regression analysis suggested that, among 4 SNPs, rs9939609 was the strongest predictor of weight gain after 6 months of risperidone treatment (p = 0.001).
Conclusions
The FTO gene polymorphisms, especially rs9939609, seem to be related to weight gain after risperidone treatment in Chinese Han patients with first episode schizophrenia.
doi:10.1186/1744-9081-10-35
PMCID: PMC4282200  PMID: 25278160
FTO gene; Weight gain; Schizophrenia; Single nucleotide polymorphism (SNP)
17.  An fMRI study of concreteness effects in spoken word recognition 
Background
Evidence for the brain mechanisms recruited when processing concrete versus abstract concepts has been largely derived from studies employing visual stimuli. The tasks and baseline contrasts used have also involved varying degrees of lexical processing. This study investigated the neural basis of the concreteness effect during spoken word recognition and employed a lexical decision task with a novel pseudoword condition.
Methods
The participants were seventeen healthy young adults (9 females). The stimuli consisted of (a) concrete, high imageability nouns, (b) abstract, low imageability nouns and (c) opaque legal pseudowords presented in a pseudorandomised, event-related design. Activation for the concrete, abstract and pseudoword conditions was analysed using anatomical regions of interest derived from previous findings of concrete and abstract word processing.
Results
Behaviourally, lexical decision reaction times for the concrete condition were significantly faster than both abstract and pseudoword conditions and the abstract condition was significantly faster than the pseudoword condition (p < 0.05). The region of interest analysis showed significantly greater activity for concrete versus abstract conditions in the left dorsolateral prefrontal cortex, posterior cingulate and bilaterally in the angular gyrus. There were no significant differences between abstract and concrete conditions in the left superior temporal gyrus or inferior frontal gyrus.
Conclusions
These findings confirm the involvement of the bilateral angular gyrus, left posterior cingulate and left dorsolateral prefrontal cortex in retrieving concrete versus abstract concepts during spoken word recognition. Significant activity was also elicited by concrete words relative to pseudowords in the left fusiform and left anterior middle temporal gyrus. These findings confirm the involvement of a widely distributed network of brain regions that are activated in response to the spoken recognition of concrete but not abstract words. Our findings are consistent with the proposal that distinct brain regions are engaged as convergence zones and enable the binding of supramodal input.
doi:10.1186/1744-9081-10-34
PMCID: PMC4243442  PMID: 25269448
Language; fMRI; Neuroimaging; Auditory lexical decision; Concrete; Abstract
18.  Multilevel analysis of facial expressions of emotion and script: self-report (arousal and valence) and psychophysiological correlates 
Background
The paper explored emotion comprehension in children with regard to facial expression of emotion. The effect of valence and arousal evaluation, of context and of psychophysiological measures was monitored. Indeed subjective evaluation of valence (positive vs. negative) and arousal (high vs. low), and contextual (facial expression vs. facial expression and script) variables were supposed to modulate the psychophysiological responses.
Methods
Self-report measures (in terms of correct recognition, arousal and valence attribution) and psychophysiological correlates (facial electromyography, EMG, skin conductance response, SCR, and heart rate, HR) were observed when children (N = 26; mean age = 8.75 y; range 6-11 y) looked at six facial expressions of emotions (happiness, anger, fear, sadness, surprise, and disgust) and six emotional scripts (contextualized facial expressions). The competencies about the recognition, the evaluation on valence and arousal was tested in concomitance with psychophysiological variations. Specifically, we tested for the congruence of these multiple measures.
Results
Log-linear analysis and repeated measure ANOVAs showed different representations across the subjects, as a function of emotion. Specifically, children’ recognition and attribution were well developed for some emotions (such as anger, fear, surprise and happiness), whereas some other emotions (mainly disgust and sadness) were less clearly represented. SCR, HR and EMG measures were modulated by the evaluation based on valence and arousal, with increased psychophysiological values mainly in response to anger, fear and happiness.
Conclusions
As shown by multiple regression analysis, a significant consonance was found between self-report measures and psychophysiological behavior, mainly for emotions rated as more arousing and negative in valence. The multilevel measures were discussed at light of dimensional attribution model.
doi:10.1186/1744-9081-10-32
PMCID: PMC4236514  PMID: 25261242
Facial expression of emotion; EMG; Valence; Psychophysiology
19.  Reduced resting-state brain activity in the default mode network in children with (central) auditory processing disorders 
Background
In recent years, there has been a growing interest in Central Auditory Processing Disorder (C)APD. However, the neural correlates of (C)APD are poorly understood. Previous neuroimaging experiments have shown changes in the intrinsic activity of the brain in various cognitive deficits and brain disorders. The present study investigated the spontaneous brain activity in (C)APD subjects with resting-state fMRI (rs-fMRI).
Methods
Thirteen children diagnosed with (C)APD and fifteen age and gender-matched controls participated in a rs-fMRI study during which they were asked to relax keeping their eyes open. Two different techniques of the rs-fMRI data analysis were used: Regional Homogeneity (ReHo) and Independent Component Analysis (ICA), which approach is rare.
Results
Both methods of data analysis showed comparable results in the pattern of DMN activity within groups. Additionally, ReHo analysis revealed increased co-activation of the superior frontal gyrus, the posterior cingulate cortex/the precuneus in controls, compared to the (C)APD group. ICA yielded inconsistent results across groups.
Conclusions
Our ReHo results suggest that (C)APD children seem to present reduced regional homogeneity in brain regions considered a part of the default mode network (DMN). These findings might contribute to a better understanding of neural mechanisms of (C)APD.
doi:10.1186/1744-9081-10-33
PMCID: PMC4236576  PMID: 25261349
Default mode network; Independent component analysis; Regional homogeneity; Functional magnetic resonance imaging; Central auditory processing disorders
20.  Age-dependent effect of high cholesterol diets on anxiety-like behavior in elevated plus maze test in rats 
Background
Cholesterol is an essential component of brain and nerve cells and is essential for maintaining the function of the nervous system. Epidemiological studies showed that patients suffering from anxiety disorders have higher serum cholesterol levels. In this study, we investigated the influence of high cholesterol diet on anxiety-like behavior in elevated plus maze in animal model and explored the relationship between cholesterol and anxiety-like behavior from the aspect of central neurochemical changes.
Methods
Young (3 weeks old) and adult (20 weeks old) rats were given a high cholesterol diet for 8 weeks. The anxiety-like behavior in elevated plus maze test and changes of central neurochemical implicated in anxiety were measured.
Results
In young rats, high cholesterol diet induced anxiolytic-like behavior, decreased serum corticosterone (CORT), increased hippocampal brain-derived neurotrophic factor (BDNF), increased hippocampal mineralocorticoid receptor (MR) and decreased glucocorticoid receptor (GR). In adult rats, high cholesterol diet induced anxiety-like behavior and increase of serum CORT and decrease of hippocampal BDNF comparing with their respective control group that fed the regular diet.
Discussion
High cholesterol diet induced age-dependent effects on anxiety-like behavior and central neurochemical changes. High cholesterol diet might affect the central nervous system (CNS) function differently, and resulting in different behavior performance of anxiety in different age period.
doi:10.1186/1744-9081-10-30
PMCID: PMC4158000  PMID: 25179125
High cholesterol; Anxiety-like behavior; Age-dependent; Hippocampus; Corticosterone; BDNF
21.  Intra-hippocampal administration of ZIP alleviates depressive and anxiety-like responses in an animal model of posttraumatic stress disorder 
Background
Given that impairment of fear extinction has been implicated in the pathogenesis of posttraumatic stress disorder (PTSD), effective pharmacological interventions that facilitate fear extinction may provide alternative strategies to conventional treatment. It is generally accepted that the zeta inhibitory peptide (ZIP), a controversial inhibitor of protein kinase M zeta (PKMζ), could erase certain types of previously established long-term memories. However, it is unclear whether ZIP administration may alleviate PTSD-associated depressive and anxiety-like abnormalities.
Methods
Here we developed a re-stressed single-prolonged stress (SPS) paradigm, a modified prevalent animal model of PTSD, and assayed the expressions of PKMζ in the hippocampus after SPS procedure. Next, Seven days prior to re-stress, ZIP was injected into the hippocampus, and the depressive and anxiety-like behavior was examined by the subsequent forced swim (FS), open-field and elevated plus maze (EPM) test.
Results
Rats given ZIP prior to FS exhibited a reduction of immobility time in FS test, and more open arms (OA) entries and longer OA duration in EPM. They also spent longer time in the center of the open field.
Conclusions
Our results suggested that re-stressed SPS could reproduce behavioral alteration similar to that observed in patients with PTSD, and these behavioral symptoms co-morbid with PTSD could be effectively alleviated by the intro-hippocampal administration of ZIP.
doi:10.1186/1744-9081-10-28
PMCID: PMC4158004  PMID: 25178800
Posttraumatic stress disorder; Single prolonged stress; ZIP; PKMζ
22.  Mathematical anxiety is linked to reduced cognitive reflection: a potential road from discomfort in the mathematics classroom to susceptibility to biases 
Background
When asked to solve mathematical problems, some people experience anxiety and threat, which can lead to impaired mathematical performance (Curr Dir Psychol Sci 11:181–185, 2002). The present studies investigated the link between mathematical anxiety and performance on the cognitive reflection test (CRT; J Econ Perspect 19:25–42, 2005). The CRT is a measure of a person’s ability to resist intuitive response tendencies, and it correlates strongly with important real-life outcomes, such as time preferences, risk-taking, and rational thinking.
Methods
In Experiments 1 and 2 the relationships between maths anxiety, mathematical knowledge/mathematical achievement, test anxiety and cognitive reflection were analysed using mediation analyses. Experiment 3 included a manipulation of working memory load. The effects of anxiety and working memory load were analysed using ANOVAs.
Results
Our experiments with university students (Experiments 1 and 3) and secondary school students (Experiment 2) demonstrated that mathematical anxiety was a significant predictor of cognitive reflection, even after controlling for the effects of general mathematical knowledge (in Experiment 1), school mathematical achievement (in Experiment 2) and test anxiety (in Experiments 1–3). Furthermore, Experiment 3 showed that mathematical anxiety and burdening working memory resources with a secondary task had similar effects on cognitive reflection.
Conclusions
Given earlier findings that showed a close link between cognitive reflection, unbiased decisions and rationality, our results suggest that mathematical anxiety might be negatively related to individuals’ ability to make advantageous choices and good decisions.
doi:10.1186/1744-9081-10-31
PMCID: PMC4166027  PMID: 25179230
Cognitive reflection test; Decision making; Dual-task manipulation; Heuristics and biases; Mathematical anxiety; Numeracy; Rationality; Test anxiety; Working memory
23.  Stuttering candidate genes DRD2 but not SLC6A3 is associated with developmental dyslexia in Chinese population 
Background
Dyslexia is a polygenic developmental disorder characterized by difficulties in reading and spelling despite normal intelligence, educational backgrounds and perception. Increasing evidences indicated that dyslexia may share similar genetic mechanisms with other speech and language disorders. We proposed that stuttering candidate genes, DRD2 and SLC6A3, might be associated with dyslexia.
Methods and results
The study was conducted in an unrelated Chinese cohort with 502 dyslexic cases and 522 healthy controls. In total, 23 Tag SNPs covering the two genes were selected for genotyping through Tagger program. Association analysis was performed on each SNP alone and in haplotypes. One SNP markers in DRD2 showed significant association with developmental dyslexia.
Conclusion
These findings indicate that polymorphism of DRD2 gene may be a risk factor of developmental dyslexia in the Chinese population.
doi:10.1186/1744-9081-10-29
PMCID: PMC4236612  PMID: 25178928
Dyslexia; Dopamine D2 receptor (DRD2); Solute carrier family 6, member 3 (SLC6A3); Linkage study
24.  An evaluation of traffic-awareness campaign videos: empathy induction is associated with brain function within superior temporal sulcus 
Acting appropriately within social contexts requires an ability to appreciate others’ mental and emotional states. Indeed, some campaign programs designed to reduce anti-social behaviour seek to elicit empathy for the victims. The effectiveness of these campaigns can be evaluated according to the degree to which they induce such responses, but by applying neuroscientific techniques this can be done at the behavioural and neurophysiological level. Neuroimaging studies aimed at identifying the neural mechanisms behind such socio-cognitive and -emotional processes frequently reveal the role of the superior temporal sulcus (STS). We applied this knowledge to assess the effectiveness of traffic-awareness campaign adverts to induce empathic expression. Functional magnetic resonance imaging (fMRI) data were acquired from 20 healthy male volunteers as they watched these campaign videos consisting of a dramatic sequence of events and catastrophic endings, and control videos without such dramatic endings. Among other structures, a significantly greater neural response was observed within bilateral STS, particularly within the right hemisphere, during the observation of campaign relative to control videos. Furthermore, activation in these brain regions correlated with the subjects’ empathic expression. Our results develop our understanding of the role of STS in social cognition. Moreover, our data demonstrate the utility of neuroscientific methods when evaluating the effectiveness of campaign videos in terms of their ability to elicit empathic responses. Our study also demonstrates the utility of these specific stimuli for future neuroscientific research.
doi:10.1186/1744-9081-10-27
PMCID: PMC4149038  PMID: 25118071
fMRI; Traffic-awareness campaign; STS; Socio-emotional processing
25.  Polymorphisms in genes implicated in dopamine, serotonin and noradrenalin metabolism suggest association with cerebrospinal fluid monoamine metabolite concentrations in psychosis 
Background
Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are the major monoamine metabolites in the central nervous system (CNS). Their cerebrospinal fluid (CSF) concentrations, reflecting the monoamine turnover rates in CNS, are partially under genetic influence and have been associated with schizophrenia. We have hypothesized that CSF monoamine metabolite concentrations represent intermediate steps between single nucleotide polymorphisms (SNPs) in genes implicated in monoaminergic pathways and psychosis.
Methods
We have searched for association between 119 SNPs in genes implicated in monoaminergic pathways [tryptophan hydroxylase 1 (TPH1), TPH2, tyrosine hydroxylase (TH), DOPA decarboxylase (DDC), dopamine beta-hydroxylase (DBH), catechol-O-methyltransferase (COMT), monoamine oxidase A (MAOA) and MAOB] and monoamine metabolite concentrations in CSF in 74 patients with psychotic disorder.
Results
There were 42 nominally significant associations between SNPs and CSF monoamine metabolite concentrations, which exceeded the expected number (20) of nominal associations given the total number of tests performed. The strongest association (p = 0.0004) was found between MAOB rs5905512, a SNP previously reported to be associated with schizophrenia in men, and MHPG concentrations in men with psychotic disorder. Further analyses in 111 healthy individuals revealed that 41 of the 42 nominal associations were restricted to patients with psychosis and were absent in healthy controls.
Conclusions
The present study suggests that altered monoamine turnover rates in CNS reflect intermediate steps in the associations between SNPs and psychosis.
doi:10.1186/1744-9081-10-26
PMCID: PMC4123495  PMID: 25073638
Psychosis; Schizophrenia; Psychiatric genetics; Cerebrospinal fluid; Homovanillic acid (HVA); 5-hydroxyindoleacetic acid (5-HIAA); 3-methoxy-4-hydroxyphenylglycol (MHPG)

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