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author:("Zhou, jinfeng")
1.  Electrical Stimulation over Bilateral Occipito-Temporal Regions Reduces N170 in the Right Hemisphere and the Composite Face Effect 
PLoS ONE  2014;9(12):e115772.
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that can modulate cortical excitability. Although the clinical value of tDCS has been advocated, the potential of tDCS in cognitive rehabilitation of face processing deficits is less understood. Face processing has been associated with the occipito-temporal cortex (OT). The present study investigated whether face processing in healthy adults can be modulated by applying tDCS over the OT. Experiment 1 investigated whether tDCS can affect N170, a face-sensitive ERP component, with a face orientation judgment task. The N170 in the right hemisphere was reduced in active stimulation conditions compared with the sham stimulation condition for both upright faces and inverted faces. Experiment 2 further demonstrated that tDCS can modulate the composite face effect, a type of holistic processing that reflects the obligatory attention to all parts of a face. The composite face effect was reduced in active stimulation conditions compared with the sham stimulation condition. Additionally, the current polarity did not modulate the effect of tDCS in the two experiments. The present study demonstrates that N170 can be causally manipulated by stimulating the OT with weak currents. Furthermore, our study provides evidence that obligatory attention to all parts of a face can be affected by the commonly used tDCS parameter setting.
doi:10.1371/journal.pone.0115772
PMCID: PMC4274090  PMID: 25531112
2.  Processing Deficits of Motion of Contrast-Modulated Gratings in Anisometropic Amblyopia 
PLoS ONE  2014;9(11):e113400.
Several studies have indicated substantial processing deficits for static second-order stimuli in amblyopia. However, less is known about the perception of second-order moving gratings. To investigate this issue, we measured the contrast sensitivity for second-order (contrast-modulated) moving gratings in seven anisometropic amblyopes and ten normal controls. The measurements were performed with non-equated carriers and a series of equated carriers. For comparison, the sensitivity for first-order motion and static second-order stimuli was also measured. Most of the amblyopic eyes (AEs) showed reduced sensitivity for second-order moving gratings relative to their non-amblyopic eyes (NAEs) and the dominant eyes (CEs) of normal control subjects, even when the detectability of the noise carriers was carefully controlled, suggesting substantial processing deficits of motion of contrast-modulated gratings in anisometropic amblyopia. In contrast, the non-amblyopic eyes of the anisometropic amblyopes were relatively spared. As a group, NAEs showed statistically comparable performance to CEs. We also found that contrast sensitivity for static second-order stimuli was strongly impaired in AEs and part of the NAEs of anisometropic amblyopes, consistent with previous studies. In addition, some amblyopes showed impaired performance in perception of static second-order stimuli but not in that of second-order moving gratings. These results may suggest a dissociation between the processing of static and moving second-order gratings in anisometropic amblyopia.
doi:10.1371/journal.pone.0113400
PMCID: PMC4237427  PMID: 25409477
3.  A Functional Polymorphism in the 3'-UTR of PXR Interacts with Smoking to Increase Lung Cancer Risk in Southern and Eastern Chinese Smoker 
Pregnane X receptor (PXR) is an important member of the nuclear receptor superfamily that copes with various endobiotic and xenobiotic stimuli, such as carcinogens by regulating an array of environmental response genes. Low PXR expression has been shown to promote tumor initiation and metastasis. The aim of the current study was to investigate whether the single nucleotide polymorphisms (SNPs) of PXR could alter lung cancer susceptibility in Chinese by affecting the function or expression of PXR. We genotyped three putatively functional SNPs of PXR (i.e., rs3814055C>T, rs3732360C>T, and rs3814058C>T) and analyzed their associations with lung cancer risk in a two-stage case-control study with a total of 1559 lung cancer cases and 1679 controls in the southern and eastern Chinese population. We found that in comparison to the rs3814058CC common genotype, the rs3814058T variants (TC/TT) which is located in the 3'-untranslated region (3'-UTR) of PXR conferred a consistently increased risk of lung cancer in both the southern Chinese (odd ratios (OR) = 1.24, 95% confidence interval (CI) = 1.03−1.49) and the eastern Chinese (OR = 1.33, 95% CI = 1.02−1.75). The variants also significantly interacted with smoking on increasing cancer risk (p = 0.023). Moreover, lung cancer tissues with the rs3814058T variants showed significantly lower PXR expression than those with rs3814058CC genotype in the smokers (p = 0.041). These results suggested that the rs3814058C>T polymorphism of PXR interacts with smoking on increasing lung cancer risk in Chinese smokers, which might be a functional genetic biomarker for lung cancer.
doi:10.3390/ijms151017457
PMCID: PMC4227172  PMID: 25268617
pregnane X receptor (PXR); lung cancer; susceptibility
4.  A Newfound Association between MDC1 Functional Polymorphism and Lung Cancer Risk in Chinese 
PLoS ONE  2014;9(9):e106794.
Mediator of DNA damage checkpoint protein 1 (MDC1) plays an early and core role in Double-Strand Break Repair (DDR) and ataxia telangiectasia-mutated (ATM) mediated response to DNA double-strand breaks (DSBs), and thus involves the pathogenesis of several DNA damage-related diseases such as cancer. We hypothesized that the single nucleotide polymorphisms (SNPs) of MDC1 which have potencies on affecting MDC1 expression or function were associated with risk of lung cancer. In a two-stage case-control study, we tested the association between 5 putatively functional SNPs of MDC1 and lung cancer risk in a southern Chinese population, and validated the promising association in an eastern Chinese population. We found the SNP rs4713354A>C that is located in the 5′-untranslated region of MDC1 was significantly associated with lung cancer risk in both populations (P = 0.024), with an odds ratio as 1.23(95% confidence interval  = 1.35–1.26) for the rs4713354C (CA+CC) genotypes compared to the rs4713354AA genotype. However, no significant association was observed between other SNPs and lung cancer risk. The gene-based analysis rested with these SNPs suggested the MDC1 as a susceptible gene for lung cancer (P = 0.009). Moreover, by querying the gene expression database, we further found that the rs4713354C genotypes confer a significantly lower mRNA expression of MDC1 than the rs4713354AA genotype in 260 cases of lymphoblastoid cells (P = 0.002). Our data suggested that the SNP rs4713354A>C of MDC1 may be a functional genetic biomarker for susceptibility to lung cancer in Chinese.
doi:10.1371/journal.pone.0106794
PMCID: PMC4157800  PMID: 25198518
5.  A Polymorphism rs12325489C>T in the LincRNA-ENST00000515084 Exon Was Found to Modulate Breast Cancer Risk via GWAS-Based Association Analyses 
PLoS ONE  2014;9(5):e98251.
Breast cancer, one of the most common malignancies diagnosed among women worldwide, is a complex polygenic disease in the etiology of which genetic factors play an important role. Thus far, a subset of breast cancer genetic susceptibility loci has been addressed among Asian woman through genome-wide association studies (GWASs). In this study, we identified numerous long, intergenic, noncoding RNAs (lincRNAs) enriched in these breast cancer risk-related loci and identified 16 single nucleotide polymorphisms (SNPs) located within the sequences of lincRNA exonic regions. We examined whether these 16 SNPs are associated with breast cancer risk in 2539 cancer patients and 2818 control subjects from eastern, southern, and northern Chinese populations. We found that the C allele of the rs12325489C>T polymorphism in the exonic regions of lincRNA-ENST00000515084 was associated with a significantly increased risk of breast cancer (adjusted odds ratio [OR] = 1.79; 95% confidence interval [CI] = 1.50–2.12), compared with the rs12325489TT genotype. Biochemical analysis demonstrated that the C to T base change at rs12325489C>T disrupts the binding site for miRNA-370, thereby influencing the transcriptional activity of lincRNA-ENST00000515084 in vitro and in vivo, and affecting cell proliferation and tumor growth. Our findings indicate that the rs12325489C>T polymorphism in the lincRNA-ENST00000515084 exon may be a genetic modifier in the development of breast cancer.
doi:10.1371/journal.pone.0098251
PMCID: PMC4039483  PMID: 24879036
6.  Immature visual neural system in children reflected by contrast sensitivity with adaptive optics correction 
Scientific Reports  2014;4:4687.
This study aimed to explore the neural development status of the visual system of children (around 8 years old) using contrast sensitivity. We achieved this by eliminating the influence of higher order aberrations (HOAs) with adaptive optics correction. We measured HOAs, modulation transfer functions (MTFs) and contrast sensitivity functions (CSFs) of six children and five adults with both corrected and uncorrected HOAs. We found that when HOAs were corrected, children and adults both showed improvements in MTF and CSF. However, the CSF of children was still lower than the adult level, indicating the difference in contrast sensitivity between groups cannot be explained by differences in optical factors. Further study showed that the difference between the groups also could not be explained by differences in non-visual factors. With these results we concluded that the neural systems underlying vision in children of around 8 years old are still immature in contrast sensitivity.
doi:10.1038/srep04687
PMCID: PMC3986699  PMID: 24732728
7.  Cerebral Activity to Opposite-Sex Voices Reflected by Event-Related Potentials 
PLoS ONE  2014;9(4):e94976.
Human voice is a gender discriminating cue and is important to mate selection. This study employed electrophysiological recordings to examine whether there is specific cerebral activity when presented with opposite-sex voices as compared to same-sex voices. Male voices and female voices were pseudo-randomly presented to male and female participants. In Experiment 1, participants were instructed to determine the gender of each voice. A late positivity (LP) response around 750 ms after voice onset was elicited by opposite-sex voices, as reflected by a positive deflection of the ERP to opposite-sex voices than that to same-sex voices. This LP response was prominent around parieto-occipital recording sites, and it suggests an opposite-sex specific process, which may reflect emotion- and/or reward-related cerebral activity. In Experiment 2, participants were instructed to press a key when hearing a non-voice pure tone and not give any response when they heard voice stimuli. In this task, no difference were found between the ERP to same-sex voices and that to opposite-sex voices, suggesting that the cerebral activity to opposite-sex voices may disappear without gender-related attention. These results provide significant implications on cognitive mechanisms with regard to opposite-sex specific voice processing.
doi:10.1371/journal.pone.0094976
PMCID: PMC3984274  PMID: 24727971
8.  Noise Provides New Insights on Contrast Sensitivity Function 
PLoS ONE  2014;9(3):e90579.
Sensitivity to luminance difference, or contrast sensitivity, is critical for animals to survive in and interact with the external world. The contrast sensitivity function (CSF), which measures visual sensitivity to spatial patterns over a wide range of spatial frequencies, provides a comprehensive characterization of the visual system. Despite its popularity and significance in both basic research and clinical practice, it hasn’t been clear what determines the CSF and how the factors underlying the CSF change in different conditions. In the current study, we applied the external noise method and perceptual template model to a wide range of external noise and spatial frequency (SF) conditions, and evaluated how the various sources of observer inefficiency changed with SF and determined the limiting factors underlying the CSF. We found that only internal additive noise and template gain changed significantly with SF, while the transducer non-linearity and coefficient for multiplicative noise were constant. The 12-parameter model provided a very good account of all the data in the 200 tested conditions (86.5%, 86.2%, 89.5%, and 96.4% for the four subjects, respectively). Our results suggest a re-consideration of the popular spatial vision model that employs the CSF as the front-end filter and constant internal additive noise across spatial frequencies. The study will also be of interest to scientists and clinicians engaged in characterizing spatial vision deficits and/or developing rehabilitation methods to restore spatial vision in clinical populations.
doi:10.1371/journal.pone.0090579
PMCID: PMC3953123  PMID: 24626135
9.  Binocular Combination of Second-Order Stimuli 
PLoS ONE  2014;9(1):e84632.
Phase information is a fundamental aspect of visual stimuli. However, the nature of the binocular combination of stimuli defined by modulations in contrast, so-called second-order stimuli, is presently not clear. To address this issue, we measured binocular combination for first- (luminance modulated) and second-order (contrast modulated) stimuli using a binocular phase combination paradigm in seven normal adults. We found that the binocular perceived phase of second-order gratings depends on the interocular signal ratio as has been previously shown for their first order counterparts; the interocular signal ratios when the two eyes were balanced was close to 1 in both first- and second-order phase combinations. However, second-order combination is more linear than previously found for first-order combination. Furthermore, binocular combination of second-order stimuli was similar regardless of whether the carriers in the two eyes were correlated, anti-correlated, or uncorrelated. This suggests that, in normal adults, the binocular phase combination of second-order stimuli occurs after the monocular extracting of the second-order modulations. The sensory balance associated with this second-order combination can be obtained from binocular phase combination measurements.
doi:10.1371/journal.pone.0084632
PMCID: PMC3880315  PMID: 24404180
10.  Declined contrast sensitivity of neurons along the visual pathway in aging cats 
Changes in the visual cortex appear to mediate much of the visual degradation during normal aging. However, how aging affects different stages along the visual pathway is unclear. In the current study, the contrast response function, one of the most important properties of neurons from early visual areas to high brain areas, was systematically compared along the visual pathway, including the lateral geniculate nucleus (LGN), early visual cortices (A17 and A18), and posteromedial lateral suprasylvian cortex (PMLS, analog to the medial temporal area (MT) in monkeys) of young and old cats. We found that the effects of aging on the LGN were negligible, whereas those in the striate cortex were substantial, with even more severe degradation in the PMLS. Reduced contrast sensitivity of neurons in the three cortical areas was accompanied by enhanced maximal visual response, increased spontaneous activity, and decreased signal-to-noise ratio, while LGN neurons exhibited largely normal response properties. Our results suggested that there was a progressively greater effect of aging on neurons at successively higher stages in the visual pathway.
doi:10.3389/fnagi.2014.00163
PMCID: PMC4089086  PMID: 25071569
aging; cat; contrast sensitivity; degeneration; visual pathway
11.  Functional Genetic Polymorphisms in PP2A Subunit Genes Confer Increased Risks of Lung Cancer in Southern and Eastern Chinese 
PLoS ONE  2013;8(10):e77285.
Protein phosphatase-2A (PP2A) is one of the major cellular serine-threonine phosphatases and functions as a tumor suppressor that negatively regulates the activity of some oncogenic kinases. Recent studies have reported that PP2A expression was suppressed during lung carcinogenesis, we there hypothesized that the single nucleotide polymorphisms (SNPs) in PP2A subunit genes may affect PP2A function and thus contribute to lung cancer susceptibility. In a two-stage case-control study with a total of 1559 lung cancer patients and 1679 controls, we genotyped eight putative functional SNPs and one identified functional SNP (i.e., rs11453459) in seven major PP2A subunits (i.e., PPP2R1A, PPP2R1B, PPP2CA, PPP2R2A, PPP2R2B, PPP2R5C, PPP2R5E) in southern and eastern Chinese. We found that rs11453459G (-G/GG) variant genotypes of PPP2R1A and the rs1255722AA variant genotype of PPP2R5E conferred increased risks of lung cancer (rs11453459, -G/GG vs. –: OR = 1.31, 95% CI = 1.13–1.51; rs1255722, AA vs. AG/GG: OR = 1.27, 95% CI = 1.07–1.51). After combined the two variants, the number of the adverse genotypes was positively associated with lung cancer risk in a dose-response manner (Ptrend  = 5.63×10−6). Further functional assay showed that lung cancer tissues carrying rs1255722AA variant genotype had a significantly lower mRNA level of PPP2R5E compared with tissues carrying GG/GA genotypes. However, such effect was not observed for the other SNPs and other combinations. Our findings suggested that the two functional variants in PPP2R1A and PPP2R5E and their combination are associated with lung cancer risk in Chinese, which may be valuable biomarkers to predict risk of lung cancer.
doi:10.1371/journal.pone.0077285
PMCID: PMC3812212  PMID: 24204789
12.  Tri-modal microscopy with multiphoton and optical coherence microscopy/tomography for multi-scale and multi-contrast imaging 
Biomedical Optics Express  2013;4(9):1584-1594.
Multi-scale multimodal microscopy is a very useful technique by providing multiple imaging contrasts with adjustable field of views and spatial resolutions. Here, we present a tri-modal microscope combining multiphoton microscopy (MPM), optical coherence microscopy (OCM) and optical coherence tomography (OCT) for subsurface visualization of biological tissues. The advantages of the tri-modal system are demonstrated on various biological samples. It enables the visualization of multiple intrinsic contrasts including scattering, two-photon excitation fluorescence (TPEF), and second harmonic generation (SHG). It also enables a rapid scanning over a large tissue area and a high resolution zoom-in for cellular-level structures on regions of interest. The tri-modal microscope can be important for label-free imaging to obtain a sufficient set of parameters for reliable sample analysis.
doi:10.1364/BOE.4.001584
PMCID: PMC3771829  PMID: 24049679
(180.4315) Nonlinear microscopy; (140.7090) Ultrafast lasers; (110.4500) Optical coherence tomography; (170.3880) Medical and biological imaging
13.  Characterizing refractive index and thickness of biological tissues using combined multiphoton microscopy and optical coherence tomography 
Biomedical Optics Express  2012;4(1):38-50.
We present a noninvasive method for characterizing the refractive index (RI) and thickness distribution in biological tissues using a combined multiphoton microscopy (MPM) and optical coherence tomography (OCT) system. Tissue layers are distinguished by the MPM and OCT images, and the RI and thickness of each layer are determined by analyzing the co-registered MPM and OCT images. The precision of this method is evaluated on four standard samples which are water, air, immersion oil and cover glass. Precision of within ~1% error compared to reference values is obtained. Biological tissue measurement is demonstrated on fish cornea. Three layers are detected, which are identified as the epithelium and stroma I and II of the cornea. The corresponding RI of each layer is measured to be ~1.446–1.448, 1.345–1.372, and 1.392–1.436, respectively. The difference of RI in the three layers correlates with the tissue compositions including cells in epithelium, large collagen fiber bundles in stroma I, and small collagen fibers in stroma II. The combined MPM/OCT technique is shown to be able to distinguish tissue layers through biochemically specific contrasts and measure RI and thickness of tissue layers at different depths.
doi:10.1364/BOE.4.000038
PMCID: PMC3539195  PMID: 23304646
(180.4315) Nonlinear microscopy; (170.4500) Optical coherence tomography; (120.5710) Refraction
14.  Functional Polymorphisms of CHRNA3 Predict Risks of Chronic Obstructive Pulmonary Disease and Lung Cancer in Chinese 
PLoS ONE  2012;7(10):e46071.
Recently, several genome-wide association studies (GWAS) have identified many susceptible single nucleotide polymorphisms (SNPs) for chronic obstructive pulmonary disease (COPD) and lung cancer which are two closely related diseases. Among those SNPs, some of them are shared by both the diseases, reflecting there is possible genetic similarity between the diseases. Here we tested the hypothesis that whether those shared SNPs are common predictor for risks or prognosis of COPD and lung cancer. Two SNPs (rs6495309 and rs1051730) located in nicotinic acetylcholine receptor alpha 3 (CHRNA3) gene were genotyped in 1511 patients with COPD, 1559 lung cancer cases and 1677 controls in southern and eastern Chinese populations. We found that the rs6495309CC and rs6495309CT/CC variant genotypes were associated with increased risks of COPD (OR = 1.32, 95% C.I. = 1.14–1.54) and lung cancer (OR = 1.57; 95% CI = 1.31–1.87), respectively. The rs6495309CC genotype contributed to more rapid decline of annual Forced expiratory volume in one second (FEV1) in both COPD cases and controls (P<0.05), and it was associated with advanced stages of COPD (P = 0.033); the rs6495309CT/CC genotypes conferred a poor survival for lung cancer (HR = 1.41, 95%CI = 1.13–1.75). The luciferase assays further showed that nicotine and other tobacco chemicals had diverse effects on the luciferase activity of the rs6495309C or T alleles. However, none of these effects were found for another SNP, rs1051730G>A. The data show a statistical association and suggest biological plausibility that the rs6495309T>C polymorphism contributed to increased risks and poor prognosis of both COPD and lung cancer.
doi:10.1371/journal.pone.0046071
PMCID: PMC3463594  PMID: 23056235
15.  CD44 rs13347 C>T polymorphism predicts breast cancer risk and prognosis in Chinese populations 
Breast Cancer Research : BCR  2012;14(4):R105.
Introduction
It has been demonstrated that the interplay of adhesion molecule CD44 and its ligands can regulate cancer cell proliferation, migration and invasion, as well as tumor-associated angiogenesis and is related to breast cancer patient survival. In this two-stage, case control study, we determined whether common functional tagSNPs (single nucleotide polymorphisms) are associated with breast cancer risk and prognosis.
Methods
Five tagSNPs of CD44 (rs10836347C>T, rs13347C>T, rs1425802A>G, rs11821102G>A, rs713330T>C) were selected and genotyped in 1,853 breast cancer patients and 1,992 healthy control subjects in Eastern and Southern populations. Potential function of rs13347C>T and association between this variation and breast cancer were further studied.
Results
Compared with the most common rs13347CC genotype, variant genotypes (CT and TT) increased an individual's susceptibility to breast cancer, especially in estrogen receptor (ER) negative patients (odds ratio (OR) = 1.37, 95%CI = 1.17 to 1.59 for ER positive patients; OR = 2.37, 95% CI = 2.00 to 2.80 for ER negative patients). We also found that rs13347CT+ TT genotypes predicts lower five-year survival rate (hazard ratio (HR) = 1.85, 95% CI = 1.09 to 3.15, P = 0.023), with the lowest survival probability in ER negative T allele carriers. Furthermore, our reporter assay findings, although preliminary and rather modest, showed that miR-509-3p may suppress CD44 expression more strongly in C allele carriers than T allele carriers (P < 0.01). Similarly, rs13347 variant genotypes (CT and TT) carriers were shown to have more CD44 expression than CC carriers in both immunohistochemistry (P < 0.001) and western blotting (P = 0.001) results.
Conclusion
These findings suggest that CD44 rs13347C>T polymorphism may affect breast cancer development and prognosis by increasing CD44 expression.
doi:10.1186/bcr3225
PMCID: PMC3680922  PMID: 22788972
16.  The eye limits the brain's learning potential 
Scientific Reports  2012;2:364.
The concept of a critical period for visual development early in life during which sensory experience is essential to normal neural development is now well established. However recent evidence suggests that a limited degree of plasticity remains after this period and well into adulthood. Here, we ask the question, "what limits the degree of plasticity in adulthood?" Although this limit has been assumed to be due to neural factors, we show that the optical quality of the retinal image ultimately limits the brain potential for change. We correct the high-order aberrations (HOAs) normally present in the eye's optics using adaptive optics, and reveal a greater degree of neuronal plasticity than previously appreciated.
doi:10.1038/srep00364
PMCID: PMC3326633  PMID: 22509464
17.  Deficient Binocular Combination Reveals Mechanisms of Anisometropic Amblyopia: Signal Attenuation and Interocular Inhibition 
Journal of Vision  2011;11(6):10.1167/11.6.4 4.
Amblyopia is a developmental disorder that results in deficits of monocular and binocular vision. It's presently unclear whether these deficits result from attenuation of signals in the amblyopic eye, inhibition by signals in the fellow eye, or both. In this study, we characterize the mechanisms underlying anisometropic amblyopia using a binocular phase and contrast combination paradigm and a contrast-gain control model. Subjects dichoptically viewed two slightly different images and reported the perceived contrast and phase of the resulting cyclopean percept. We found that the properties of binocular combination were abnormal in many aspects, which is explained by a combination of (1) attenuated monocular signal in the amblyopic eye, (2) stronger interocular contrast-gain control from the fellow eye to the signal in amblyopic eye (direct interocular inhibition), and (3) stronger interocular contrast-gain control from the fellow eye to the contrast gain control signal from the amblyopic eye (indirect interocular inhibition). We conclude that anisometropic amblyopia led to both monocular and interocular deficits. A complete understanding of the mechanisms underlying amblyopia requires studies of both monocular deficits and binocular interactions.
doi:10.1167/11.6.4
PMCID: PMC3324098  PMID: 21546609
18.  Visual Perceptual Learning 
Perceptual learning refers to the phenomenon that practice or training in perceptual tasks often substantially improves perceptual performance. Often exhibiting stimulus or task specificities, perceptual learning differs from learning in the cognitive or motor domains. Research on perceptual learning reveals important plasticity in adult perceptual systems, and as well as the limitations in the information processing of the human observer. In this article, we review the behavioral results, mechanisms, physiological basis, computational models, and applications of visual perceptual learning.
doi:10.1016/j.nlm.2010.09.010
PMCID: PMC3021105  PMID: 20870024
19.  Training in Contrast Detection Improves Motion Perception of Sinewave Gratings in Amblyopia 
In this study, training in spatial vision led to improvements in motion perception of sinewave gratings in amblyopia. The results provide new empirical support for perceptual learning as a potential treatment for amblyopia.
Purpose.
One critical concern about using perceptual learning to treat amblyopia is whether training with one particular stimulus and task generalizes to other stimuli and tasks. In the spatial domain, it has been found that the bandwidth of contrast sensitivity improvement is much broader in amblyopes than in normals. Because previous studies suggested the local motion deficits in amblyopia are explained by the spatial vision deficits, the hypothesis for this study was that training in the spatial domain could benefit motion perception of sinewave gratings.
Methods.
Nine adult amblyopes (mean age, 22.1 ± 5.6 years) were trained in a contrast detection task in the amblyopic eye for 10 days. Visual acuity, spatial contrast sensitivity functions, and temporal modulation transfer functions (MTF) for sinewave motion detection and discrimination were measured for each eye before and after training. Eight adult amblyopes (mean age, 22.6 ± 6.7 years) served as control subjects.
Results.
In the amblyopic eye, training improved (1) contrast sensitivity by 6.6 dB (or 113.8%) across spatial frequencies, with a bandwidth of 4.4 octaves; (2) sensitivity of motion detection and discrimination by 3.2 dB (or 44.5%) and 3.7 dB (or 53.1%) across temporal frequencies, with bandwidths of 3.9 and 3.1 octaves, respectively; (3) visual acuity by 3.2 dB (or 44.5%). The fellow eye also showed a small amount of improvement in contrast sensitivities and no significant change in motion perception. Control subjects who received no training demonstrated no obvious improvement in any measure.
Conclusions.
The results demonstrate substantial plasticity in the amblyopic visual system, and provide additional empirical support for perceptual learning as a potential treatment for amblyopia.
doi:10.1167/iovs.11-7541
PMCID: PMC3176008  PMID: 21693615
20.  THE EFFECTS OF AGING ON THE STRENGTH OF SURROUND SUPPRESSION OF RECEPTIVE FIELD OF V1 CELLS IN MONKEYS 
Neuroscience  2010;169(2):874-881.
The surround suppression of the receptive field is important for basic visual information processing, such as orientation specificity. To date, the effects of aging on the strength of surround suppression are not clear. To address this issue, we carried out extracellular single-unit studies of the receptive field properties of cells in the primary visual cortex (area V1) in young and old rhesus (Macaca mulatta) monkeys. When presented with the oriented central stimulus, we found that cells in old animals showed reduced orientation and direction selectivity compared with those in young animals. When presented with the oriented central stimulus together with the optimal surround stimulus, more selective cells {orientation bias (OB) ≥ 0.1; a bias of 0.1 is significant at the P < 0.005 level} in animals of both ages showed reduced orientation selectivity compared with the experiment that presented only the oriented central stimulus. When presented with the optimal central stimulus together with the oriented surround stimulus, cells in old animals showed reduced orientation and direction selectivity compared with young animals. Moreover, broadly tuned cells (OB<0.1) in old animals exhibited significantly reduced suppression indices that quantified the strength of the surround suppression of the receptive field, when compared with those in young animals. These results suggest that aging may seriously affect the surround suppression of the receptive field of V1 cells. Thus, the decreased strength of surround suppression of the receptive field may be one possible reason for the decreased stimulus selectivity of V1 cells previously found in the senescent brain. This work will contribute to an understanding of the physiological mechanisms mediating surround suppression of the receptive field.
doi:10.1016/j.neuroscience.2010.05.015
PMCID: PMC2910096  PMID: 20472034
primary visual cortex; orientation selectivity; receptive field; surround inhibition; rhesus monkey
21.  Perceptual Learning Improves Contrast Sensitivity of V1 Neurons in Cats 
Current biology : CB  2010;20(10):887-894.
Summary
Background
Perceptual learning has been documented in adult humans over a wide range of tasks. Although the often observed specificity of learning is generally interpreted as evidence for training-induced plasticity in early cortical areas, physiological evidence for training-induced changes in early visual cortical areas is modest, despite reports of learning-induced changes of cortical activities in fMRI studies. To reveal the physiological bases of perceptual learning, we combined psychophysical measurements with extracellular single-unit recording under anesthetized preparations, and examined the effects of training in grating orientation identification on both perceptual and neuronal contrast sensitivity functions of cats.
Results
We have found that training significantly improved perceptual contrast sensitivity of the cats to gratings with the spatial frequencies near the ‘trained’ spatial frequency, with stronger effects in the trained eye. Consistent with behavioral assessments, the mean contrast sensitivity of neurons recorded from V1 of the trained cats was significantly higher than that of neurons recorded from the untrained cats. Furthermore, in the trained cats, the contrast sensitivity of V1 neurons responding preferentially to stimuli presented via the trained eyes was significantly greater than that of neurons responding preferentially to stimuli presented via the ‘untrained’ eyes. The effect was confined to the trained spatial frequencies. In both trained and untrained cats, the neuronal contrast sensitivity functions derived from the contrast sensitivity of the individual neurons were highly correlated with behaviorally determined perceptual contrast sensitivity functions.
Conclusions
We suggest that training-induced neuronal contrast-gain in area V1 underlies behaviorally determined perceptual contrast sensitivity improvements.
doi:10.1016/j.cub.2010.03.066
PMCID: PMC2877770  PMID: 20451388
22.  Contrast and Phase Combination in Binocular Vision 
PLoS ONE  2010;5(12):e15075.
Background
How the visual system combines information from the two eyes to form a unitary binocular representation of the external world is a fundamental question in vision science that has been the focus of many psychophysical and physiological investigations. Ding & Sperling (2006) measured perceived phase of the cyclopean image, and developed a binocular combination model in which each eye exerts gain control on the other eye's signal and over the other eye's gain control. Critically, the relative phase of the monocular sine-waves plays a central role.
Methodology/Principal Findings
We used the Ding-Sperling paradigm but measured both the perceived contrast and phase of cyclopean images in three hundred and eighty combinations of base contrast, interocular contrast ratio, eye origin of the probe, and interocular phase difference. We found that the perceived contrast of the cyclopean image was independent of the relative phase of the two monocular gratings, although the perceived phase depended on the relative phase and contrast ratio of the monocular images. We developed a new multi-pathway contrast-gain control model (MCM) that elaborates the Ding-Sperling binocular combination model in two ways: (1) phase and contrast of the cyclopean images are computed in separate pathways, although with shared cross-eye contrast-gain control; and (2) phase-independent local energy from the two monocular images are used in binocular contrast combination. With three free parameters, the model yielded an excellent account of data from all the experimental conditions.
Conclusions/Significance
Binocular phase combination depends on the relative phase and contrast ratio of the monocular images but binocular contrast combination is phase-invariant. Our findings suggest the involvement of at least two separate pathways in binocular combination.
doi:10.1371/journal.pone.0015075
PMCID: PMC3000330  PMID: 21151558
23.  The Role of Interleukin-15 Polymorphisms in Adult Acute Lymphoblastic Leukemia 
PLoS ONE  2010;5(10):e13626.
Background
Interleukin-15 (IL-15) plays important roles in the immune system and in the development of hematopoietic cells. Previous studies revealed that five SNPs in IL-15, rs10519612, rs10519613, rs35964658, rs17007695 and rs17015014, were significantly associated with childhood Acute Lymphoblastic Leukemia (ALL) treatment response. In adult ALL, the expression of IL-15 was also correlated with the immunophenotypes of ALL. Therefore, we hypothesize that SNPs of IL-15 might also be associated with adult ALL.
Methods and Findings
We genotyped the above five SNPs of IL-15 gene by PCR-RFLP assays in adult ALL case-control studies. The current study included 121 adult ALL patients and 263 healthy controls. IL-15 genotypes and haplotypes were determined and the associations with the risk of ALL were analyzed by logistic regression. SNPs rs10519612 and rs17007695 were significantly associated with ALL (P = 0.013 and P = 0.001). We observed a 2-fold and 2.4-fold excess risk of developing ALL for the rs10519612 CC and rs17007695 TC genotype carriers compared with non-carriers, respectively. Haplotype analysis revealed that haplotypes ACAC, CAGT and CCAT were significantly associated with adult B-ALL, while haplotype CCAT conferred susceptibility to T-ALL.
Conclusion
These findings suggest that IL-15 gene polymorphisms are significantly associated with ALL in adult Chinese population.
doi:10.1371/journal.pone.0013626
PMCID: PMC2963612  PMID: 21049047
24.  Association between the Cytotoxic T-Lymphocyte Antigen 4 +49G > A polymorphism and cancer risk: a meta-analysis 
BMC Cancer  2010;10:522.
Background
As a key gene in the immunosurveillance of cell malignancy, Cytotoxic T-lymphocyte antigen 4 (CTLA-4 is an important negative regulator of T cell activation and proliferation. The CTLA-4 +49G > A polymorphism is one of the most commonly studied polymorphisms in this gene due to its association with cancer risks, but previous results have been conflicting.
Methods
We preformed a meta-analysis using 22 eligible case-control studies (including 32 datasets) with a total of 11,273 patients and 13,179 controls to summarize the existing data on the association between the CTLA-4 +49G > A polymorphism and cancer risk.
Results
Compared with the common CTLA-4 +49G > A GG genotype, the carriers of variant genotypes (CTLA-4 +49 GC/CC) had a 1.24-fold elevated risk of cancer (95% CI = 1.18-1.32, P < 0.05) under the dominant genetic model, as estimated using a fixed effect model. The effect of the CTLA-4 +49G > A polymorphism was further evaluated using stratification analysis. In four breast cancer studies, patients with the variant genotypes had a significantly increased risk of breast cancer (OR = 1.31, 95% CI = 1.17-1.48, P < 0.00001). A similar result was found in three skin cancer studies (OR = 1.30, 95% CI = 1.10-1.52, P = 0.001). In 26 solid tumor studies, subjects with the variant genotypes had a significantly higher risk of developing solid tumors (OR = 1.25, 95% CI = 1.18-1.33, P < 0.00001) compared with the 6 non-solid tumor studies (OR = 1.08, 95% CI = 0.79-1.48, P = 0.62). Patients with variant genotypes had significantly increased risk of non-epithelial tumors and epithelial tumors, with ORs of 1.23 (95% CI = 1.14-1.32, P < 0.00001) and 1.29 (95% CI = 1.17-1.41, P < 0.00001), respectively. It was also demonstrated that the increased risk of cancer associated with CTLA-4 +49G > A variant genotypes was more pronounced in Caucasians (OR = 1.29, 95% CI = 1.13-1.47, P = 0.0002), Asians (OR = 1.23, 95% CI = 1.16-1.32, P < 0.00001) and Chinese (OR = 1.23, 95% CI = 1.15-1.31, P < 0.00001).
Conclusion
Our meta-analysis suggests that the CTLA-4 +49G > A polymorphism genotypes (GA + AA) might be associated with an increased risk of cancer, especially in Caucasians and Chinese.
doi:10.1186/1471-2407-10-522
PMCID: PMC2958938  PMID: 20920330
25.  Aging Affects the Neural Representation of Speed in Macaque Area MT 
Cerebral Cortex (New York, NY)  2008;19(9):1957-1967.
Human perception of speed declines with age. Much of the decline is probably mediated by changes in the middle temporal (MT) area, an extrastriate area whose neural activity is linked to the perception of speed. In the present study, we used random-dot patterns to study the effects of aging on speed-tuning curves in cortical area MT of macaque visual cortex. Our results provide evidence for a significant degradation of speed selectivity in MT. Cells in old animals preferred lower speeds than did those in young animals. Response modulation and discriminative capacity for speed in old monkeys were also significantly weaker than those in young ones. Concurrently, MT cells in old monkeys showed increased baseline responses, peak responses and response variability, and these changes were accompanied by decreased signal-to-noise ratios. We also found that speed discrimination thresholds in old animals were higher than in young ones. The foregoing neural changes may mediate the declines in visual motion perception that occur during senescence.
doi:10.1093/cercor/bhn221
PMCID: PMC2733681  PMID: 19037080
aging; area MT; degradation; inhibition; macaque; speed

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