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Prism adaptation (PA) is a promising rehabilitation technique for visuo-spatial neglect, an attention disorder that is characterized by spatial attention deficits (i.e., deficits in orienting). PA involves visuo-motor adaptation to rightward shifting prism goggles. Following goggle removal, this adaptation results in leftward shifts in visuo-motor aiming and amelioration of spatial neglect. Even though some studies clearly support the beneficial effects of PA for spatial neglect, not all studies find benefits, thus it remains unclear how PA effects could be improved. Taking advantage of the known interactions between orienting and alerting reported in the attention literature (i.e., alerting enhances orienting function; e.g., Ishigami and Klein in J Individ Differ 30:220-237. doi: 10.1027/1614-0001.30.4.220 , 2009, in J Neurosci Methods 190:117-28. doi: 10.1016/j.jneumeth.2010.04.019 , 2010; Robertson et al. in Nature 395:169-72. doi: 10.1038/25993 , 1998), we examined the effects of alerting tones on PA with healthy young and older adults. We found that the effects of alerting on PA with young adults were negative, while there was a positive effect with older adults, specifically on a visuo-motor outcome task. Thus, enhancement of PA effects by alerting may be age specific and task specific. Therefore, we can conclude that while the impact of alerting tones is not always positive, further research in patients with neglect may be warranted.

The current study examined the robustness, stability, reliability, and isolability of the attention network scores (alerting, orienting, and executive control) when young children experienced repeated administrations of the child version of the Attention Network Test (ANT; Rueda et al., 2004). Ten test sessions of the ANT were administered to 12 young children. Participants were asked to indicate the direction of a target fish, flanked by distractors, presented either above or below the fixation cross following different types of visual cues. Network scores, reflecting alerting, orienting, and executive control, were calculated using orthogonal subtractions of performance in selected conditions. Only the alerting network scores remained highly significant across the 10 sessions. The executive network scores showed some practice effects. The reliability of the network scores remained poor regardless of the amount of data. Based on the results, use of the ANT is cautioned against in young children when repe...

Impairments in information processing speed are common in multiple sclerosis (MS), with affected individuals demonstrating slower responses and more intraindividual variability (IIV) in their performance on timed tasks. Evidence suggesting that IIV provides novel information about cognitive deficits in MS is accumulating; however, little is known about the stability of IIV across multiple assessments. In this study, we investigated IIV in response speed in persons with MS across 6 monthly sessions using the Attention Network Test-Interaction (ANT-I).Individuals with relatively mild relapsing remitting MS and healthy controls completed the ANT-I at 6 monthly intervals. Clinical assessments (Sessions 1 and 6) and conventional magnetic resonance imaging (MRI) studies (Sessions 1-6) were examined for individuals with MS.The MS group's clinical and neuroimaging measures were stable during the 6-month period. Individuals with MS were slower and more variable in reaction time performance on the ANT-I than were controls. Differences in IIV between groups were maintained across the 6 sessions, with IIV demonstrating less susceptibility to across-session practice effects than mean latency scores.IIV provides a stable measure of cognitive performance in mildly affected persons with MS who are clinically and radiologically stable. Further studies exploring its utility as a clinical outcome are warranted.

Many biological activities of green tea have been attributed to a major constituent, (-)-epigallocatechin gallate (EGCG). We previously reported that EGCG and a catechin-rich green tea beverage modulated the gene expression of gluconeogenic enzymes, glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), in the mouse liver. However, it remains to be examined whether or not a constituent other than EGCG contributes to the change in gene expression of these enzymes. In this study, we separated the hot water infusion of green tea leaves (GT) into an ethanol-soluble fraction (GT-E) and an EGCG-free water-soluble fraction (GT-W), and examined their effects using rat hepatoma H4IIE cells. The inclusion of GT, GT-E, and GT-W in the culture medium reduced the gene expression of G6Pase and PEPCK. GT-W caused a decrease in expression of the transcription factor HNF4α. Reduced levels of PEPCK and HNF4α proteins were demonstrated in the cells treated with GT-W. GT-W showed an activity similar to insulin, but different from EGCG. Administration of GT-W to mice for 4 weeks reduced the hepatic expression of G6Pase, PEPCK, and HNF4α. These results suggest that green tea contains some component(s) with insulin-like activity distinguishable from EGCG and that drinking green tea may help to prevent diabetes.

Auditory saltation is the orderly misperception of the spatial location of repetitive click stimuli emitted from two successive locations when the inter-click intervals (ICIs) are sufficiently short. The clicks are perceived as originating not only from the actual source locations, but also from locations between them. In two tasks, the present experiment compared free-field auditory saltation for 90 degrees excursions centered in the frontal, rear, left and right acoustic hemifields, by measuring the ICI at which subjects report 50% illusion strength (subjective task) and the ICI at which subjects could not distinguish real motion from saltation (objective task). A comparison of the saltation illusion for excursions spanning the midline (i.e. for frontal or rear hemifields) with that for stimuli in the lateral hemifields (left or right) revealed that the illusion was weaker for the midline-straddling conditions (i.e. the illusion was restricted to shorter ICIs). This may reflect the contribution of two perceptual channels to the task in the midline conditions (as opposed to one in the lateral hemifield conditions), or the fact that the temporal dynamics of localization differ between the midline and lateral hemifield conditions. A subsidiary comparison of saltation supported in the left and right auditory hemifields, and therefore by the right and left auditory forebrains, revealed no difference.

Prism adaptation (PA) is both a perceptual-motor learning task as well as a promising rehabilitation tool for visuo-spatial neglect (VSN) – a spatial attention disorder often experienced after stroke resulting in slowed and/or inaccurate motor responses to contralesional targets. During PA, individuals are exposed to prism-induced shifts of the visual-field while performing a visuo-guided reaching task. After adaptation, with goggles removed, visuo-motor responding is shifted to the opposite direction of that initially induced by the prisms. This visuo-motor aftereffect has been used to study visuo-motor learning and adaptation and has been applied clinically to reduce VSN severity by improving motor responding to stimuli in contralesional (usually left-sided) space. In order to optimize PA’s use for VSN patients, it is important to elucidate the neural and cognitive processes that alter visuomotor function during PA. In the present study, healthy young adults underwent PA while event-related potentials (ERPs) were recorded at the termination of each reach (screen-touch), then binned according to accuracy (hit vs. miss) and phase of exposure block (early, middle, late). Results show that two ERP components were evoked by screen-touch: an early error-related negativity (ERN), and a P300. The ERN was consistently evoked on miss trials during adaptation, while the P300 amplitude was largest during the early phase of adaptation for both hit and miss trials. This study provides evidence of two neural signals sensitive to visual feedback during PA that may sub-serve changes in visuomotor responding. Prior ERP research suggests that the ERN reflects an error processing system in medial-frontal cortex, while the P300 is suggested to reflect a system for context updating and learning. Future research is needed to elucidate the role of these ERP components in improving visuomotor responses among individuals with VSN.

The Attention Network Test (ANT) is a frequently used computer-based tool for measuring the three attention networks (alerting, orienting, and executive control). We examined the psychometric properties of performance on a variant of the ANT, the Attention Network Test-Interaction (ANT-I) in healthy older adults (N = 173; mean age = 65.4, SD = 6.5; obtained from the Brain in Motion Study, Tyndall et al. BMC Geriatr 13:21, 2013. doi: 10.1186/1471-2318-13-21) to evaluate its usefulness as a measurement tool in both aging and clinical research. In terms of test reliability, split-half correlation analyses showed that all network scores were significantly reliable, although the strength of the correlations varied across networks as seen before (r = 0.29, 0.70, and 0.68, for alerting, orienting, and executive networks, respectively, p’s < 0.05). In terms of construct validity, ANOVAs confirmed that each network score was significant (18.3, 59.4, and 109.2 ms for the alerting, orienting, and executive networks, respectively, p’s < 0.01) and that these scores were generally independent from each other. Importantly, for criterion validity, a series of hierarchical linear regressions showed that the executive network score, in addition to demographic information, was a significant predictor of performance on tests of conflict resolution as well as verbal memory and retrieval (β = −0.165 and −0.184, p’s < 0.05, respectively). These results provide new information regarding the reliability and validity of ANT-I test performance in a healthy older adult population. The results provide insights into the psychometrics of the ANT-I and its potential utility in clinical research settings.

The Attention Network Test (ANT) assesses the networks of attention (alerting, orienting, and executive control). The utility of measuring attention network performances with the repeated administration of the ANT in clinical populations has not yet been explored. In the present study, we administered a variant of the ANT (ANT-I) to 11 multiple sclerosis (MS) patients and 11 controls over six monthly sessions to examine the stability, isolability, robustness, and reliability of the ANT-I. Participants responded through button presses to indicate the direction of a target arrow presented either above or below a fixation cross. The target was accompanied by distracting arrows, pointing either in the same or opposite direction of the target arrow. Target arrows were preceded in some trials by alerting auditory signals and/or by uninformative visual cues. Network scores were calculated using orthogonal subtractions of performance under selected conditions. The MS patients were slower than the controls, though group differences in network performance were rare. Even after five test sessions, the network scores remained stable, despite some practice effects that were the largest under conditions that tested the executive network. The reliabilities of the orienting and executive network effects were good in both groups and increased across sessions, especially with the MS patients. The alerting network was the least reliable, especially for MS patients, but it also became more reliable across sessions. The results suggest that the ANT-I can be used to measure the integrity of attention networks for MS patients in applications that require repeated testing.

Ishigami and Klein (2010) showed that scores of the three attention networks (alerting, orienting, and executive control) measured with the two versions of the Attention Network Test (ANT; Fan et al., 2002; Callejas et al., 2005) were robust over 10 sessions of repeated testing even though practice effects were consistently observed especially in the executive network when young adults were tested. The current study replicated their method to examine robustness, stability, reliability, and isolability of the networks scores when older adults were tested with these ANTs. Ten test sessions, each containing two versions of the ANT, were administered to 10 older adults. Participants were asked to indicate the direction of a target arrow, flanked by distractors, presented either above or below the fixation following auditory signals or/and visual cue. Network scores were calculated using orthogonal subtractions of performance in selected conditions. All network scores remained highly significant even after nine previous sessions despite some practice effects in the executive and the alerting networks. Some lack of independence among the networks was found. The relatively poor reliability of network scores with one session of data rises to respectable levels as more data is added.

Green tea has been shown to have many beneficial health effects. We have previously reported that dietary (-)-epigallocatechin-3-O-gallate (EGCG), the major polyphenol in green tea, reduced gene expressions of gluconeogenic enzymes, glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), in the normal mouse liver. In the present study, we examined the effects of intragastrical administration of EGCG on the expression of gluconeogenesis-related genes in the mouse intestine. The results of experiments with the semi-quantitative reverse transcription-polymerase chain reaction indicated that EGCG at 0.6 mg/head caused a reduced expression of G6Pase, PEPCK, hepatocyte nuclear factor 1α (HNF1α), and HNF4α. Experiments using the quantitative real-time polymerase chain reaction confirmed these effects. We then examined the effects of EGCG using human colon carcinoma Caco-2 cells stimulated with dexamethasone and dibutyryl cAMP. The results were generally consistent with those from the experiments in vivo. The present findings suggest EGCG to contribute to the beneficial effects of green tea on diabetes, obesity, and cancer by modulating gene expression in the intestine.

Rat hepatoma H4IIE cells were stimulated with dexamethasone and dibutyryl cAMP to increase gene expressions of gluconeogenic enzymes, glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK). Inclusion of catechin-rich green tea beverage (GTB) in the culture medium reduced the up-regulation of these genes as well as that of hepatocyte nuclear factor 4 alpha (HNF4alpha) gene. GTB was fractionated into chloroform-soluble (Fraction I), ethyl acetatesoluble (Fraction II), methanol-soluble (Fraction III) and residual (Fraction IV) fractions. Fractions II and III containing catechins caused an attenuation of the up-regulated expression of these genes as well as the down-regulation of HNF4alpha gene expression. Fraction IV had a synergistic effect on the up-regulation by dexamethasone/dibutyryl cAMP of the PEPCK gene expression and upregulated HNF4alpha gene expression. These results suggest that GTB down-regulated the expression of the HNF4alpha gene to cause the down-regulated gene expression of gluconeogenic enzymes. One reason why GTB did not down-regulate hepatic PEPCK gene expression in previous animal experiments may be that the component(s) acting to up-regulate PEPCK gene expression was more effective in vivo than in cultured cells.

The importin/exportin transport system provides the machinery involved in nucleocytoplasmic transport. Alterations of the levels of importins and exportins may play crucial roles in development, differentiation and transformation. Employing human leukaemia HL-60 cells, we and others have revealed the differentiation-associated changes in the protein and gene expression of these factors. The recent finding that a switch to the importin-alpha subtype triggers neural differentiation of embryonic stem cells underscores the importance of nucleocytoplasmic transport factors in cellular events. This review focuses on current research into the roles of importins and exportins in cell differentiation.

Employing the DNA microarray technique, we previously reported the alteration in gene expression of nucleocytoplasmic transport factors, importins and exportins, induced by 1,25-dihydroxyvitamin D3 (DVD) in human leukemia HL-60 cells. Here, we used the quantitative reverse transcription-polymerase chain reaction method to confirm such previous findings, and compared them with those from the cells treated with all-trans-retinoic acid (ATRA). The results indicated that the gene expression of the transport factors examined was mostly down-regulated following differentiation induced by DVD and ATRA, but importin alpha5 gene expression was up-regulated in either case. The differences were found in the gene expression of importin alpha3 and exportin 6 between the cells after treatments with DVD and ATRA. These variations may be related to the difference between HL-60 cell lineages differentiating into monocytes/macrophages and granulocytes. The present findings provide further evidence to support the important roles of importins and exportins in cell differentiation.