Comparison and combination of gamified neurofeedback training and general behavioral training.

With the rapid development of the international community, foreign language learning has become increasingly important. Listening training is a particularly important component of foreign language learning. The most difficult aspect of listening training is the development of speech discrimination ability, which is crucial to speech perception. General behavioral training requires a substantial amount of time and attention. To address this, we previously developed a neurofeedback (NF) training system that enables unconscious learning of auditory discrimination. However, to our knowledge, no studies have compared NF training and general behavioral training. In the present study, we compared the learning effects of NF training, general behavioral training, and a combination of both strategies. Specifically, we developed a gamified and adapted NF training of auditory discrimination. We found that both NF training and general behavioral training enhanced behavioral performance, whereas only NF training elicited significant changes in brain activity. Furthermore, the participants that used both training methods exhibited the largest improvement in behavioral performance. This indicates that the combined use of NF and general behavioral training methods may be optimal for enhancing auditory discrimination ability when learning foreign languages.

Low alanine aminotransferase levels are independently associated with mortality risk in patients with atrial fibrillation.

Extremely low alanine aminotransferase (ALT) may reflect aging, frailty, sarcopenia, and malnutrition in several cardiovascular diseases, but the association between low ALT and patient characteristics, cardiovascular and all-cause mortality is not well investigated in the population with atrial fibrillation. We conducted a post hoc analysis of a prospective, observational multicenter study. Patients with nonvalvular AF in the SAKURA AF Registry (n = 3156) were classified into 3 tertiles according to baseline ALT: first (ALT ≤ 15 U/L, n = 1098), second (15 < ALT < 23 U/L, n = 1055), and third (ALT ≥ 23 U/L, n = 1003). The first tertile had an older age; lower body mass index (BMI); higher prevalence of heart failure; and lower hemoglobin, total cholesterol, and triglycerides (all P < 0.05). During median 39.2 months follow-up, the first tertile had significantly higher incidences of cardiovascular and all-cause mortality (log-rank P < 0.001). Lower ALT was significantly associated with the incidence of cardiovascular and all-cause mortality, even after adjusting for clinically relevant factors (P < 0.05). Low ALT may reflect aging, sarcopenia, and malnutrition and be independently associated with a high risk of all-cause mortality in patients with AF.

Galvanic Vestibular Stimulation-Based Prediction Error Decoding and Channel Optimization.

A significant problem in brain-computer interface (BCI) research is decoding - obtaining required information from very weak noisy electroencephalograph signals and extracting considerable information from limited data. Traditional intention decoding methods, which obtain information from induced or spontaneous brain activity, have shortcomings in terms of performance, computational expense and usage burden. Here, a new methodology called prediction error decoding was used for motor imagery (MI) detection and compared with direct intention decoding. Galvanic vestibular stimulation (GVS) was used to induce subliminal sensory feedback between the forehead and mastoids without any burden. Prediction errors were generated between the GVS-induced sensory feedback and the MI direction. The corresponding prediction error decoding of the front/back MI task was validated. A test decoding accuracy of 77.83-78.86% (median) was achieved during GVS for every 100[Formula: see text]ms interval. A nonzero weight parameter-based channel screening (WPS) method was proposed to select channels individually and commonly during GVS. When the WPS common-selected mode was compared with the WPS individual-selected mode and a classical channel selection method based on correlation coefficients (CCS), a satisfactory decoding performance of the selected channels was observed. The results indicated the positive impact of measuring common specific channels of the BCI.

Behavioral effect of mismatch negativity neurofeedback on foreign language learning.

Listening is critical for foreign language learning. Listening difficulties can occur because of an inability to perceive or recognize sounds while listening to speech, whereas successful listening can boost understanding and improve speaking when learning a foreign language. Previous studies in our laboratory revealed that EEG-neurofeedback (NF) using mismatch negativity event-related brain potential successfully induced unconscious learning in terms of auditory discrimination of speech sounds. Here, we conducted a feasibility study with a small participant group (NF group and control group; six participants each) to examine the practical effects of mismatch negativity NF for improving the perception of speech sounds in a foreign language. Native Japanese speakers completed a task in which they learned to perceive and recognize spoken English words containing the consonants "l" or "r". Participants received neurofeedback training while not explicitly attending to auditory stimuli. The results revealed that NF training significantly improved the proportion of correct in discrimination and recognition trials, even though the training time for each word pair was reduced to 20% of the training time reported in our previous study. The learning effect was not affected by training with three pairs of words with different vowels. The current results indicate that NF resulted in long-term learning that persisted for at least 2 months.

Association of patient satisfaction with direct oral anticoagulants and the clinical outcomes: Findings from the SAKURA AF registry.

BACKGROUND: The burden or benefit of anticoagulation treatment affects patient satisfaction, which may in turn affect the adherence to the treatment and subsequent outcomes. Thus, we hypothesized that the patient satisfaction with direct oral anticoagulants (DOACs) may influence the clinical outcome in patients with atrial fibrillation (AF). METHODS AND RESULTS: We investigated the clinical outcomes among 719 DOAC users (age 71.9 ± 9.1 years, 184 females, and 449 persistent AF) enrolled in the SAKURA AF Registry who completed a satisfaction questionnaire with anticoagulation therapy by means of the Anti-Clot Treatment Scale (ACTS), which included 12-item burden and 3-item benefit scales. During a 41.8-month-follow-up, a stroke/systemic embolism (SE) occurred in 27 patients (3.8%) and major bleeding events in 25 (3.5%). A univariate Cox regression analysis revealed that an older age, persistent AF, higher CHA2DS2-VASc score, no history of AF ablation, lower creatinine clearance, and lower ACTS benefit scores were significantly associated with an increased risk of a stroke/SE, but not with major bleeding events. A low benefit score remained an independent predictor of a stroke/SE even after a multivariate adjustment. The ACTS burden scores were not associated with any clinical events. CONCLUSIONS: We found a strong association between a low benefit satisfaction and increased stroke risk. We should follow patients carefully to educate them on treatment importance for patients unsatisfied with the benefits of DOACs for stroke prevention.

Impact of the Fibrosis-4 Index on Risk Stratification of Cardiovascular Events and Mortality in Patients with Atrial Fibrillation: Findings from a Japanese Multicenter Registry.

BACKGROUND: Liver diseases drive the development and progression of atrial fibrillation (AF). The Fibrosis-4 (FIB4) index is a non-invasive scoring method for detecting liver fibrosis, but the prognostic impact of using it for AF patients is still unknown. Herein, we evaluated using the FIB4 index as a risk assessment tool for cardiovascular events and mortality in patients with AF. METHODS: We performed a post-hoc analysis of a prospective, observational multicenter study. A total of 3067 patients enrolled in a multicenter Japanese registry were grouped as first tertile (FIB4 index < 1.75, n = 1022), second tertile (1.75 ≤ FIB4 index < 2.51, n = 1022), and third tertile (FIB4 index ≥ 2.51, n = 1023). RESULTS: The third tertile had statistically significant results: older age, lower body mass index, increased heart failure prevalence, and lower clearances of hemoglobin and creatinine (all p < 0.05). During the follow-up period, incidences of major bleeding, cardiovascular events, and all-cause mortality were significantly higher for the third tertile (all p < 0.05). After multivariate adjustment, the third tertile associated independently with cardiovascular events (HR 1.72; 95% CI 1.31-2.25) and all-cause mortality (HR 1.43; 95% CI 1.06-1.95). Adding the FIB4 index to a baseline model with CHA2DS2-VASc score improved the prediction of cardiovascular events and all-cause mortality, as shown by the significant increase in the C-statistic (all p < 0.05), net reclassification improvement (all p < 0.001), and integrated discrimination improvement (all p < 0.001). A FIB4 index ≥ 2.51 most strongly associated with cardiovascular events and all-cause mortality in AF patients with high CHADS2 scores (all p < 0.001). CONCLUSIONS: The FIB4 index is independently associated with risks of cardiovascular events and all-cause mortality in AF patients.

Comparison of continuous 24-h and 14-day monitoring for detection of otherwise unknown atrial fibrillation: a registry to identify Japanese concealed atrial fibrillation (REAL-AF)-based study.

Early detection of atrial fibrillation (AF) is desirable for preventing strokes. Not only does AF often go undetected in patients being followed up for various disease conditions, but the optimal detection method also remains to be elucidated. In a prospective observational study of 24-h Holter monitoring versus 14-day external loop recording performed for detection of previously undiagnosed AF in 868 Japanese outpatients (aged 75 ± 6 years), with a CHA2DS2-vasc score ≥ 1, but no prior AF episodes, AF was detected during the initial monitoring period in 16 (1.8%) patients, in 7 (1.1% [7/645]) by 24-h monitoring and 9 (4.0% [9/223]) by 14-day monitoring (P = 0.005), and overall in 32 (3.7%) during the 1-year study period. Absence of a beta-blocker therapy and the serum N-terminal pro-brain natriuretic peptide level were independent predictors of a new detection of AF. Oral anticoagulation (OAC) therapy was given to 22 (69%) of the 32 patients in whom AF was detected, and no difference in the incidence of subsequent major adverse events was found between the patients managed with and without oral OAC therapy. Previously unknown AF was documented at a prevalence of 3.7% per year among Japanese with a notable CHA2DS2-VASc score, and 14-day external loop monitoring was significantly more effective for detection of the disorder. A large-scale prospective AF screening study conducted to clarify the type or types of patients who would benefit from "early" OAC therapy for primary stroke prevention is warranted.

Correlation between Aortic Calcification Score and Biochemical Parameters in Hemodialysis Patients.

BACKGROUND: The purpose of this study was to determine the correlation between aortic calcification and demographic and biochemical parameters in hemodialysis patients. SUMMARY: Calcification scores of the aortic arch and abdominal aorta were determined from multi-slice computed tomography scans and evaluated according to the Agatston score. The associations between demographic and biochemical parameters and aortic calcification score were determined. In total, 190 patients were included in the study. There was a significant positive correlation between aortic calcification scores and age, duration of hemodialysis, cardiothoracic ratio, normalized protein catabolic rate, brachial-ankle pulse wave velocity (baPWV), serum markers of mineral metabolism, and inflammation. A significant negative correlation was found between aortic calcification scores and platelet count. Multivariate analysis showed that age, duration of hemodialysis, baPWV, phosphate, calcium and phosphate (Ca×P) product, parathyroid hormone, and C-reactive protein levels were independent risk factors for calcification of the aortic arch, while baPWV and Ca×P product were independent risk factors for calcification of the abdominal aorta. Key Messages: Aortic calcification scores correlate with age, duration of hemodialysis, and several biochemical parameters of inflammation and mineral metabolism.

Efficacy of L-carnitine supplementation for improving lean body mass and physical function in patients on hemodialysis: a randomized controlled trial.

BACKGROUND: Carnitine deficiency is common in patients on hemodialysis. However, the efficacy of L-carnitine supplementation for improving lean body mass (LBM) and physical function has not yet been evaluated. METHODS: In this multicenter, prospective, parallel, randomized, controlled trial, 91 patients on hemodialysis who developed carnitine deficiency were randomly assigned to receive injections of 1,000 mg L-carnitine 3 times per week after each hemodialysis session (L-carnitine group) or no injections (control group) with monitoring for 12 months. RESULTS: The data for 84 of the 91 patients were available for analysis (L-carnitine group, n = 42; control group, n = 42). Dry weight and body mass index did not significantly change in the L-carnitine group, but significantly decreased in the control group. Arm muscle area (AMA) did not change significantly in the L-carnitine group but decreased significantly in the control group; the difference in mean AMA between the groups was 6.22% (95% confidence interval [CI] 1.90-10.5; P = 0.037). Hand grip strength did not change significantly in the L-carnitine group, but decreased significantly in the control group. The difference in change in hand grip strength between the groups was 4.27% (95% CI 0.42-8.12; P = 0.030). Furthermore, LBM did not change significantly in the L-carnitine group but decreased significantly in the control group; the difference in mean LBM between the groups was 2.92 % (95% CI 1.28-4.61; P = 0.0007). CONCLUSIONS: L-carnitine supplementation is useful in patients who develop carnitine deficiency on hemodialysis because it maintains physical function and LBM.

Patient Satisfaction with Direct Oral Anticoagulants and Warfarin.

The burden of anticoagulation treatment affects patient satisfaction, which in turn affects adherence to treatment. Thus, we must thoroughly understand the advantages of direct oral anticoagulants (DOACs) over vitamin K antagonists (VKAs)/warfarin given for stroke prevention in patients with atrial fibrillation (AF). We compared satisfaction with anticoagulation therapy between 654 DOAC and 821 warfarin users enrolled in the SAKURA AF Registry. Satisfaction was assessed by means of the Anti-Clot Treatment Scale (ACTS), which includes 12-item burdens and 3-item benefits scales, and the treatment satisfaction questionnaire for medication II (TSQM II), which includes 2-item effectiveness, 3-item side effects, 3-item convenience, and 2-item global satisfaction domains. There were no significant between-group differences in TSQM II convenience (67.6 ± 14.5 versus 68.9 ± 14.5, P = 0.280), effectiveness (65.0 ± 13.3 versus 66.0 ± 15.0, P = 0.422), side effects (93.6 ± 13.7 versus 92.8 ± 14.4, P = 0.067), and global satisfaction (64.7 ± 14.9 versus 66.0 ± 14.6, P = 0.407) scores. In contrast, although there was no significant between-group difference in the ACTS benefits scores (9.8 ± 3.1 versus 10.1 ± 3.2, P = 0.051), the ACTS burdens scores (54.5 ± 6.3 versus 52.7 ± 6.9, P < 0.0001) were significantly higher in the DOAC users, independent of age, sex, and DOAC type. We can expect greater burden satisfaction with anticoagulation treatment in patients given a DOAC versus VKA/warfarin. The reduced burden of treatment will translate to greater patient adherence to their treatment plans and a positive effect on clinical outcomes.

Utilizing sensory prediction errors for movement intention decoding: A new methodology.

We propose a new methodology for decoding movement intentions of humans. This methodology is motivated by the well-documented ability of the brain to predict sensory outcomes of self-generated and imagined actions using so-called forward models. We propose to subliminally stimulate the sensory modality corresponding to a user's intended movement, and decode a user's movement intention from his electroencephalography (EEG), by decoding for prediction errors-whether the sensory prediction corresponding to a user's intended movement matches the subliminal sensory stimulation we induce. We tested our proposal in a binary wheelchair turning task in which users thought of turning their wheelchair either left or right. We stimulated their vestibular system subliminally, toward either the left or the right direction, using a galvanic vestibular stimulator and show that the decoding for prediction errors from the EEG can radically improve movement intention decoding performance. We observed an 87.2% median single-trial decoding accuracy across tested participants, with zero user training, within 96 ms of the stimulation, and with no additional cognitive load on the users because the stimulation was subliminal.

Galvanic Tongue Stimulation Inhibits Five Basic Tastes Induced by Aqueous Electrolyte Solutions.

Galvanic tongue stimulation (GTS) modulates taste sensation. However, the effect of GTS is contingent on the electrode polarity in the proximity of the tongue. If an anodal electrode is attached in the proximity of the tongue, an electrical or metallic taste is elicited. On the other hand, if only cathodal electrode is attached in the proximity of the tongue, the salty taste, which is induced by electrolyte materials, is inhibited. The mechanism of this taste inhibition is not adequately understood. In this study, we aim to demonstrate that the inhibition is cause by ions, which elicit taste and which migrate from the taste sensors on the tongue by GTS. We verified the inhibitory effect of GTS on all five basic tastes induced by electrolyte materials. This technology is effective for virtual reality systems and interfaces to support dietary restrictions. Our findings demonstrate that cathodal-GTS inhibits all the five basic tastes. The results also support our hypothesis that the effects of cathodal-GTS are caused by migrating tasting ions in the mouth.

Reading Traits for Dynamically Presented Texts: Comparison of the Optimum Reading Rates of Dynamic Text Presentation and the Reading Rates of Static Text Presentation.

With the growth in digital display technologies, dynamic text presentation is used widely in every day life, such as in electric advertisements and tickers on TV programs. Unlike static text reading, little is known about the basic characteristics underlying reading dynamically presented texts. Two experiments were performed to investigate this. Experiment 1 examined the optimum rate of dynamic text presentation in terms of a readability and favorability. This experiment demonstrated that, when the rate of text presentation was changed, there was an optimum presentation rate (around 6 letters/s in our condition) regardless of difficulty level. This indicates that the presentation rate of dynamic texts can affect the impression of reading. In Experiment 2, to elucidate the traits underlying dynamic text reading, we measured the reading speeds of silent and trace reading among the same participants and compared them with the optimum presentation rate obtained in Experiment 1. The results showed that the optimum rate was slower than with silent reading and faster than with trace reading, and, interestingly, the individual optimum rates of dynamic text presentation were correlated with the speeds of both silent and trace reading. In other words, the readers who preferred a fast rate in dynamic text presentation would also have a high reading speed for silent and trace reading.

Levocarnitine Injections Decrease the Need for Erythropoiesis-Stimulating Agents in Hemodialysis Patients with Renal Anemia.

AIMS: The aim of this study was to evaluate the efficacy of levocarnitine injection for renal anemia in hemodialysis patients. METHODS: In this randomized controlled clinical trial, we randomly assigned patients on maintenance hemodialysis at our hospital to receive levocarnitine injections (n = 30) or no injection (n = 30) and monitored the patients during 12 months of treatment. In the treatment group, patients received an injection of levocarnitine 1,000 mg 3 times weekly after hemodialysis sessions. All patients received recombinant human erythropoietin as an erythropoiesis-stimulating agent (ESA). Response to ESA therapy was determined by calculating the erythropoietin responsiveness index (ERI; ESA dose·kg-1·g-1· dL-1·week-1). RESULTS: (1) The target levels of hemoglobin and hematocrit were maintained during the study period in both the levocarnitine group and the control group. (2) The dose of ESAs required to maintain these levels decreased gradually in the levocarnitine group and was significantly lower at 6 and 12 months than at study initiation. Furthermore, the dose of ESAs was significantly lower than that in the control group at 12 months. (3) The ERI showed a significant decrease at 6 and 12 months in the levocarnitine group, with a significant difference between the 2 groups at 12 months. CONCLUSION: Our results suggest that levocarnitine administration can reduce the dose of ESAs required in patients with renal anemia on hemodialysis and improve the response to ESA therapy.

Unconscious improvement in foreign language learning using mismatch negativity neurofeedback: A preliminary study.

When people learn foreign languages, they find it difficult to perceive speech sounds that are nonexistent in their native language, and extensive training is consequently necessary. Our previous studies have shown that by using neurofeedback based on the mismatch negativity event-related brain potential, participants could unconsciously achieve learning in the auditory discrimination of pure tones that could not be consciously discriminated without the neurofeedback. Here, we examined whether mismatch negativity neurofeedback is effective for helping someone to perceive new speech sounds in foreign language learning. We developed a task for training native Japanese speakers to discriminate between 'l' and 'r' sounds in English, as they usually cannot discriminate between these two sounds. Without participants attending to auditory stimuli or being aware of the nature of the experiment, neurofeedback training helped them to achieve significant improvement in unconscious auditory discrimination and recognition of the target words 'light' and 'right'. There was also improvement in the recognition of other words containing 'l' and 'r' (e.g., 'blight' and 'bright'), even though these words had not been presented during training. This method could be used to facilitate foreign language learning and can be extended to other fields of auditory and clinical research and even other senses.

Levocarnitine Improves Cardiac Function in Hemodialysis Patients With Left Ventricular Hypertrophy: A Randomized Controlled Trial.

BACKGROUND: Levocarnitine deficiency in hemodialysis patients is common. Although the effect of levocarnitine therapy on uremic anemia has been studied in small trials, its effects on cardiac function remain unclear. STUDY DESIGN: Multicenter, prospective, open-label, parallel, randomized, controlled trial. SETTING & PARTICIPANTS: Patients undergoing maintenance hemodialysis with carnitine deficiency (free carnitine plasma concentration < 40µmol/L) enrolled in 3 hemodialysis centers. INTERVENTION: Random assignment to treatment for 12 months with oral levocarnitine therapy at a dose of 20mg/kg/d or control group (no levocarnitine therapy). OUTCOMES & MEASUREMENTS: Cardiac function was assessed by echocardiography. The primary end point was change in ejection fraction from baseline at the end of the study. Secondary end points included changes in left ventricular mass index and clinical parameters from baseline at the end of the study. RESULTS: 222 patients were randomly assigned, of whom 148 patients (levocarnitine group, n=75; control group, n=73) were analyzed. Ejection fraction increased from baseline to the end of the study in the levocarnitine group by 5.43% (95% CI, 4.53%-6.32%), but not in the control group (change, -0.14%; between-group difference, 5.57% [95% CI, 4.48%-6.66%]; P<0.001). Left ventricular mass index decreased from baseline to the end of the study in the levocarnitine group (change of -8.89 [95% CI, -11.7 to -6.09] g/m(2)), but not in the control group (change of 1.62g/m(2); between-group difference, 10.50 [95% CI, 7.51 to 13.60] g/m(2); P<0.001). Levocarnitine therapy reduced N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and improved the erythropoietin responsiveness index, whereas no such effects were observed in the control group. LIMITATIONS: Not a double-blinded study. CONCLUSIONS: Levocarnitine therapy is useful for hemodialysis patients with carnitine deficiency; these patients may benefit from such therapy, with amelioration of cardiac function and reduction of left ventricular mass index.

Association of restless legs syndrome with oxidative stress and inflammation in patients undergoing hemodialysis.

BACKGROUND: Restless legs syndrome (RLS) is a common comorbidity in patients undergoing hemodialysis, but clinical factors predictive of RLS risk and severity have not been identified. The aims of this multicenter cross-sectional study were to document RLS prevalence and severity in patients undergoing hemodialysis and to identify associated risk factors. METHODS: One-hundred and fifty-nine stable patients on maintenance hemodialysis were enrolled (113 men, 46 women; mean age: 68 ± 11 years; mean duration of dialysis: 54 ± 60 months). Diagnosis of RLS was based on the criteria proposed by the International Restless Legs Syndrome Study Group (IRLSSG), and RLS severity was assessed using the IRLSSG Severity Scale. Potential factors associated with RLS and IRLSSG Severity Scale score were assessed by univariate and multivariate regression analyses. RESULTS: RLS affected 22% of the study population. The RLS subgroup had a significantly longer duration of hemodialysis and higher cardiothoracic ratio compared to the non-RLS subgroup. The RLS subgroup also had significantly higher serum levels of high-sensitivity C-reactive protein, interleukin-6, ferritin, N-terminal pro-B-type natriuretic peptide, and 8-hydroxy-2'-deoxyguanosine (8-OHdG), and a significantly lower transferrin saturation level compared to the non-RLS subgroup, suggesting a chronic inflammatory state and associated oxidative stress in comorbid patients. Serum 8-OHdG level was an independent risk factor for high IRLSSG Severity Scale score. CONCLUSION: This study confirms the high prevalence of RLS among hemodialysis patients and identifies the oxidative stress marker serum 8-OHdG as a significant independent predictor of RLS severity. Further studies are needed to identify detailed risk factors and the pathophysiological role of oxidative stress in RLS.

Four-pole galvanic vestibular stimulation causes body sway about three axes.

Galvanic vestibular stimulation (GVS) can be applied to induce the feeling of directional virtual head motion by stimulating the vestibular organs electrically. Conventional studies used a two-pole GVS, in which electrodes are placed behind each ear, or a three-pole GVS, in which an additional electrode is placed on the forehead. These stimulation methods can be used to induce virtual head roll and pitch motions when a subject is looking upright. Here, we proved our hypothesis that there are current paths between the forehead and mastoids in the head and show that our invented GVS system using four electrodes succeeded in inducing directional virtual head motion around three perpendicular axes containing yaw rotation by applying different current patterns. Our novel method produced subjective virtual head yaw motions and evoked yaw rotational body sway in participants. These results support the existence of three isolated current paths located between the mastoids, and between the left and right mastoids and the forehead. Our findings show that by using these current paths, the generation of an additional virtual head yaw motion is possible.

Effects of levocarnitine on brachial-ankle pulse wave velocity in hemodialysis patients: a randomized controlled trial.

BACKGROUND AND AIMS: Atherosclerotic cardiovascular disease is the most common cause of mortality in patients with end-stage kidney disease. Chronic kidney disease patients often exhibit a deficiency in L-carnitine due to loss during hemodialysis (HD). We studied the effects of L-carnitine supplementation on brachial-ankle pulse wave velocity (baPWV), a marker of atherosclerosis, in HD patients. METHODS: This was a prospective, open-label, randomized, parallel controlled, multi-center trial testing the anti-atherosclerotic efficacy of oral L-carnitine administration (20 mg/kg/day). HD patients (n = 176, mean age, 67.2 ± 10.3 years old; mean duration of HD, 54 ± 51 months) with plasma free L-carnitine deficiency (<40 µmol/L) were randomly assigned to the oral L-carnitine group (n = 88) or control group (n = 88) and monitored during 12 months of treatment. RESULTS: There were no significant differences in baseline clinical variables between the L-carnitine and control groups. L-carnitine supplementation for 12 months significantly increased total, free, and acyl carnitine levels, and reduced the acyl/free carnitine ratio. The baPWV value decreased from 2085 ± 478 cm/s at baseline to 1972 ± 440 cm/s after six months (p < 0.05) to 1933 ± 363 cm/s after 12 months (p < 0.001) of L-carnitine administration, while no significant changes in baPWV were observed in the control group. Baseline baPWV was the only factor significantly correlated with the decrease in baPWV. CONCLUSIONS: L-carnitine supplementation significantly reduced baPWV in HD patients. L-carnitine may be a novel therapeutic strategy for preventing the progression of atherosclerotic cardiovascular disease.

Unconscious learning of auditory discrimination using mismatch negativity (MMN) neurofeedback.

Neurofeedback is a strong direct training method for brain function, wherein brain activity patterns are measured and displayed as feedback, and trainees try to stabilize the feedback signal onto certain desirable states to regulate their own mental states. Here, we introduce a novel neurofeedback method, using the mismatch negativity (MMN) responses elicited by similar sounds that cannot be consciously discriminated. Through neurofeedback training, without participants' attention to the auditory stimuli or awareness of what was to be learned, we found that the participants could unconsciously achieve a significant improvement in the auditory discrimination of the applied stimuli. Our method has great potential to provide effortless auditory perceptual training. Based on this method, participants do not need to make an effort to discriminate auditory stimuli, and can choose tasks of interest without boredom due to training. In particular, it could be used to train people to recognize speech sounds that do not exist in their native language and thereby facilitate foreign language learning.