Cognitive components of aging-related increase in word-finding difficulty.

Word-finding difficulty (WFD) is a common cognitive complaint in aging, manifesting both in natural speech and in controlled laboratory tests. Various theories of cognitive aging have addressed WFD, and understanding its underlying mechanisms can help to clarify whether it has diagnostic value for neurodegenerative disease. Two influential "information-universal" theories attribute it to rather broad changes in cognition. The processing speed theory posits a general slowdown of all cognitive processes, while the inhibitory deficit hypothesis (IDH) predicts a specific problem in suppressing irrelevant information. One "information specific" theory of language production, the transmission deficit hypothesis (TDH), posits a breakdown in retrieval of phonological word forms from a corresponding lemma. To adjudicate between these accounts, we administered an online gamified covert naming task featuring picture-word interference (PWI), previously validated to elicit similar semantic interference and phonological facilitation effects as overt naming tasks. 125 healthy adults aged 18 to 85 completed the task, along with a battery of executive function tasks and a naturalistic speech sample to quantify WFD in connected speech. PWI effects provided strong support for the TDH but limited support for IDH, in that semantic interference increased and phonological facilitation decreased across the lifespan. However, neither of these effects on single-word retrieval associated with WFD measured in connected speech. Rather, overall reaction time for word retrieval (controlling for psychomotor slowing) was the best predictor of spontaneous WFD and executive function decline, suggesting processing speed as the key factor, and that verbal reaction time may be an important clinical measure.

TAG-ME again: A serious game for measuring working memory.

BrainTagger (demo version: researcher-demo.braintagger.com) is a suite of Target Acquisition Games for Measurement and Evaluation (TAG-ME). Here we introduce TAG-ME Again, a serious game modeled after the well-established N-Back task, to assess working memory ability across three difficulty levels corresponding to 1-, 2-, and 3-back conditions. We also report on two experiments aimed at assessing convergent validity with the N-Back task. Experiment 1 examined correlations with N-Back task performance in a sample of adults (n = 31, 18-54 years old) across three measures: reaction time; accuracy; a combined RT/accuracy metric. Significant correlations between game and task were found, with the strongest relationship being for the most difficult version of the task (3-Back). In Experiment 2 (n = 66 university students, 18-22 years old), we minimized differences between the task and the game by equating stimulus-response mappings and spatial processing demands. Significant correlations were found between game and task for both the 2-Back and 3-Back levels. We conclude that TAG-ME Again is a gamified task that has convergent validity with the N-Back Task.

Longitudinal analysis of sustained performance on gamified cognitive assessment tasks.

Serious games aim to provide cognitive assessments that are more enjoyable and easier to self-administer, potentially leading to more frequent assessments. We carried out two studies examining the relationship between game-playing enjoyment, game difficulty, and cognitive (game) performance. In the first study, 16 participants played three serious games once a week over four weeks as part of an undergraduate course, but with relatively minor motivation in terms of course credits. In the second study, 14 participants played serious games over six sessions in a period of three weeks. Participants included graduate students receiving credit for the course project (a major component of the grade) and friends and family that they recruited. Performance in the more difficult tasks tended to improve over time in the second study, but not in the first. Participants from the first study showed an overall negative sentiment toward the games. However, participants from the second study enjoyed the majority of games except for the more difficult games that required players to temporarily hold and memorize information. Participants got significantly better in the more difficult working memory games, even though these games were less popular than the simpler games. Our interpretation of the results is that enjoyability is important in encouraging people to keep playing cognitive assessment games as time progresses, and that enjoyability helps in maintaining performance in easy games. Higher motivation on the other hand played a significant role in facilitating learning effects in difficult games as well as in maintaining enjoyability.

Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection: a randomized trial.

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

Picture-Word Interference Effects Are Robust With Covert Retrieval, With and Without Gamification.

The picture-word interference (PWI) paradigm has been used to investigate the time course of processes involved in word retrieval, but is challenging to implement online due to dependence on measurements of vocal reaction time. We performed a series of four experiments to examine picture-word interference and facilitation effects in a form of covert picture naming, with and without gamification. A target picture was accompanied by an audio word distractor that was either unrelated, phonologically-related, associatively-related, or categorically-related to the picture. Participants were instructed to judge whether the name of the target picture ended in the phoneme assigned to the block by pressing corresponding keys as quickly and accurately as possible. Experiments 1 and 2 successfully replicated categorical interference and phonological facilitation effects at different optimal stimulus-onset-asynchronies (SOAs) between words and pictures. Experiment 3 demonstrated that a key gamification feature (collecting coins) motivated faster speed at the expense of accuracy in the gamified vs. experimental format of the task. Experiment 4 adopted the optimal SOAs and verified that the gamification reveals expected interference and facilitation effects despite the speed-accuracy tradeoff. These studies confirmed that categorical interference occurs earlier than phonological facilitation, while both processes are independent from articulation and inherent to word retrieval itself. The covert PWI paradigm and its gamification have methodological value for neuroimaging studies in which articulatory artifacts obscure word retrieval processes, and may be developed into potential online word-finding assessments that can reveal word retrieval difficulties with greater sensitivity.

A multicenter, randomized, double-blind clinical study on Wufuxinnaoqing Soft Capsule () in treatment of chronic stable angina patients with blood stasis syndrome.

OBJECTIVE: To confirm the efficacy and safety of Wufuxinnaoqing Soft Capsule (, WSC) in the treatment of chronic stable angina (blood stasis syndrome). METHODS: A multicenter, randomized, double-blind, placebo-controlled trial with superiority test was designed. A total of 240 patients with chronic stable angina (blood stasis syndrome) from multiple centers were randomly and equally assigned to the treatment group and the control group. Based on standard treatment of Western medicine, the treatment group was given WSC, while the control group was given WSC mimetic, both for 12 weeks. Observed indicators included the efficacy in angina, the efficacy in Chinese medicine syndrome, the withdrawal or reduce rate of nitroglycerin and routine safety indices. RESULTS: After 12-week treatment, the significant effective rate and total effective rate of the treatment group were significantly better than those of the control group (23.5% vs. 9.2%, 64.7% vs. 30.8%), respectively, with statistically significant difference (P<0.01). After 12-week treatment, the decreased points and the decreased rate of angina symptom score in the treatment group were better than in the control group (5.1±4.2 points vs. 2.8±3.5 points, 44.9%±37.2% vs. 25.4%±30.7%) respectively, with significant difference (P<0.01). After 12-week treatment, the significant effective rate and total effective rate of the treatment group were better than the control group (respectively, 30.3% vs. 15.0%, 67.2% vs. 45.0%,P<0.01). After 8- or 12-week treatment, the decreased points and the decreased rate of Chinese medicine syndrome score in the treatment group were better than the control group (P<0.05 orP<0.01). After 12-week treatment, nitroglycerin withdrawal rate and the withdrawal or reduce rate in treatment group were better than the control group (P<0.01). On safety evaluation, the incidence of adverse events (7.563% vs. 7.500%) and the incidence of cardiovascular events (0.840% vs. 0.000%) in the treatment group were similar with the control group, and the difference was not statistically significant (P>0.05). CONCLUSION: In treatment of chronic stable angina (blood stasis syndrome), WSC can reduce angina attacks and consumption of nitroglycerin, decrease angina severity degree, effectively relieve the blood stasis syndromes, such as chest pain, chest tightness, palpitations, dark purple tongue and other symptoms. Besides, adverse events and cardiovascular adverse events in the treatment group and the control group showed no difference. All shows that the drug is safe and effective. [This study was registered in Chinese Clinical Trial Registry (ChiCTR), with registration number: ChiCTR-TRC-14005158.].