Cardiorespiratory rhythm-contingent trace eyeblink conditioning in elderly adults.

Learning outcome is modified by the degree to which the subject responds and pays attention to specific stimuli. Our recent research suggests that presenting stimuli in contingency with a specific phase of the cardiorespiratory rhythm might expedite learning. Specifically, expiration-diastole (EXP-DIA) is beneficial for learning trace eyeblink conditioning (TEBC) compared with inspiration-systole (INS-SYS) in healthy young adults. The aim of this study was to investigate whether the same holds true in healthy elderly adults (n = 50, aged >70 yr). Participants were instructed to watch a silent nature film while TEBC trials were presented at either INS-SYS or EXP-DIA (separate groups). Learned responses were determined as eyeblinks occurring after the tone conditioned stimulus (CS), immediately preceding the air puff unconditioned stimulus (US). Participants were classified as learners if they made at least five conditioned responses (CRs). Brain responses to the stimuli were measured by electroencephalogram (EEG). Memory for the film and awareness of the CS-US contingency were evaluated with a questionnaire. As a result, participants showed robust brain responses to the CS, acquired CRs, and reported awareness of the CS-US relationship to a variable degree. There was no difference between the INS-SYS and EXP-DIA groups in any of the above. However, when only participants who learned were considered, those trained at EXP-DIA (n = 11) made more CRs than those trained at INS-SYS (n = 13). Thus, learned performance could be facilitated in those elderly who learned. However, training at a specific phase of cardiorespiratory rhythm did not increase the proportion of participants who learned.NEW & NOTEWORTHY We trained healthy elderly individuals in trace eyeblink conditioning, either at inspiration-systole or at expiration-diastole. Those who learned exhibited more conditioned responses when trained at expiration-diastole rather than inspiration-systole. However, there was no difference between the experimental groups in the proportion of individuals who learned or did not learn.

Interactive scalp acupuncture combined with suspension digital occupational therapy for upper limb motor dysfunction after stroke: a multi-center randomized controlled trial. / äº’åŠ¨å¼å¤´é’ˆç»“åˆæ‚¬åŠä¸‹æ•°å­—ä½œä¸šç–—æ³•æ²»ç–—è„‘å’ä¸­åŽä¸Šè‚¢è¿åŠ¨åŠŸèƒ½éšœç¢ï¼šå¤šä¸­å¿ƒéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the effects of interactive scalp acupuncture on upper limb motor function and activities of daily living in patients with upper limb motor dysfunction after stroke. METHODS: One hundred and twenty patients with upper limb motor dysfunction after stroke were randomly divided into an observation group(60 cases, 2 cases dropped out)and a control group(60 cases, 1 case dropped out). Both groups were treated with routine medication and rehabilitation. The observation group was treated with interactive scalp acupuncture combined with suspension digital occupational therapy, interactive scalp acupuncture was applied at middle 2/5 of the parietal and temporal anterior oblique line, middle 2/5 of the parietal and temporal posterior oblique line and second lateral line of parietal of the hemiparalysis contralateral side, 30 min each time.The control group was treated with suspension digital occupational therapy alone. The treatment was given once a day, 5 times a week for 4 weeks in the two groups. The scores of Fugl-Meyer assessment scale of upper extremity(FMA-UE), action research arm test(ARAT), the modified Barthel index (MBI) and surface electromyography(sEMG)signal of the biceps and triceps on the affected side were observed before and after treatment in the two groups, and the clinical efficacy was evaluated. RESULTS: After treatment, the FMA-UE, ARAT and MBI scores were increased compared with those before treatment in both groups(P<0.05), the changes of the observation group were greater than those in the control group(P<0.05). After treatment, the integrated electromyography(iEMG)value and root mean square(RMS)value of the biceps and triceps on the affected side during elbow flexion and extension were increased compared with those before treatment in both groups(P<0.05), the changes of the observation group were greater than those in the control group(P<0.05). The total effective rate was 94.8%(55/58) in the observation group, which was higher than 83.1%(49/59) in the control group(P<0.05). CONCLUSIONS: Interactive scalp acupuncture could improve upper limb motor function and activities of daily living in patients with upper limb motor dysfunction after stroke.

Association of Different Combinations of ALDH2 rs671, APOE rs429358, rs7412 Polymorphisms with Hypertension in Middle-Aged and Elderly People: A Case-Control Study.

Background: Hypertensive patients have a younger trend, and studies on the role of genetic factors in hypertension susceptibility have been inconsistent. Aldehyde dehydrogenases 2 (ALDH2) and apolipoprotein E (APOE) are involved in the pathophysiological processes of hypertension. To investigate the relationship of ALDH2 and APOE polymorphisms with hypertension in middle-aged (30-59 years old) and elderly (≥60 years old) persons. Methods: Two thousand six hundred and ten hypertensive patients and 1921 controls were included (between 30 and 100 years old). The genotypes of common polymorphisms in APOE and ALDH2 genes (APOE rs429358, rs7412, and ALDH2 rs671) of the subjects were analyzed by polymerase-chain reaction (PCR)-microarray. Statistical analyses (Student's t-test, Mann-Whitney U-test, χ 2 test, and logistic regression analysis) were performed with SPSS v21.0. Results: There were 4531 participants (66.60 ± 12.10 years old) in this study, including 3057 (67.5%) males and 1474 (32.5%) females. There were no significant differences in distributions of ALDH2 rs671, APOE rs429358/rs7412 genotypes and alleles between hypertensive patients and controls. Persons with ALDH2 rs671 G/A or A/A genotype were less likely to have hypertension (G/A+A/A vs G/G: gender-, age-, smoking-, and drinking-adjusted OR 0.885, 95% CI 0.785-0.997, P=0.045), while ALDH2 rs671 A/A+APOE rs429358 or rs7412 wild-type genotype may decrease the risk of hypertension. In middle-aged group, ALDH2 rs671 G/A+APOE rs429358 T/C carriers (adjusted OR 0.547, 95% CI 0.350-0.856, P=0.008), and ALDH2 rs671 A/A+APOE rs7412 C/C genotypes (adjusted OR 0.567, 95% CI 0.361-0.891, P=0.014) were less likely to have hypertension. In elderly group, APOE rs7412 T/T carriers were more likely to have hypertension (rs671 T/T vs C/C: adjusted OR 4.755, 95% CI 1.075-21.027, P=0.040; rs671 T/T vs C/C or C/T: adjusted OR 4.734, 95% CI 1.071-20.928, P=0.040). Conclusion: Polymorphism-polymorphism interactions of ALDH2 rs671 and APOE rs429358/rs7412 may effect on hypertension susceptibility. Different genotypes comparison shows different roles in middle-aged and elderly people, respectively.

Cardiac cycle and respiration phase affect responses to the conditioned stimulus in young adults trained in trace eyeblink conditioning.

Rhythms of breathing and heartbeat are linked to each other as well as to the rhythms of the brain. Our recent studies suggest that presenting conditioned stimulus during expiration or during the diastolic phase of the cardiac cycle facilitates neural processing of that stimulus and improves learning in a conditioning task. To date, it has not been examined whether using information from both respiration and cardiac cycle phases simultaneously allows even more efficient modulation of learning. Here, we studied whether the timing of the conditioned stimulus to different cardiorespiratory rhythm phase combinations affects learning in a conditioning task in healthy young adults. The results were consistent with previous reports: timing the conditioned stimulus to diastole during expiration was more beneficial for learning than timing it to systole during inspiration. Cardiac cycle phase seemed to explain most of this variation in learning at the behavioral level. Brain-evoked potentials (N1) elicited by the conditioned stimulus and recorded using electroencephalogram were larger when the conditioned stimulus was presented to diastole during expiration than when it was presented to systole during inspiration. Breathing phase explained the variation in the N1 amplitude. To conclude, our findings suggest that noninvasive monitoring of bodily rhythms combined with closed-loop control of stimulation can be used to promote learning in humans. The next step will be to test if performance can also be improved in humans with compromised cognitive ability, such as in older people with memory impairments.NEW & NOTEWORTHY We report, for the first time, that the rhythms of breathing and the beating of the heart have a phase combination that is indicative of a neural state beneficial for cognition. This suggests that bodily rhythms not only modulate cognition but that this phenomenon can also be noninvasively harnessed to improve learning in humans.

Coherence Between Brain Activation and Speech Envelope at Word and Sentence Levels Showed Age-Related Differences in Low Frequency Bands.

Speech perception is dynamic and shows changes across development. In parallel, functional differences in brain development over time have been well documented and these differences may interact with changes in speech perception during infancy and childhood. Further, there is evidence that the two hemispheres contribute unequally to speech segmentation at the sentence and phonemic levels. To disentangle those contributions, we studied the cortical tracking of various sized units of speech that are crucial for spoken language processing in children (4.7-9.3 years old, N = 34) and adults (N = 19). We measured participants' magnetoencephalogram (MEG) responses to syllables, words, and sentences, calculated the coherence between the speech signal and MEG responses at the level of words and sentences, and further examined auditory evoked responses to syllables. Age-related differences were found for coherence values at the delta and theta frequency bands. Both frequency bands showed an effect of stimulus type, although this was attributed to the length of the stimulus and not the linguistic unit size. There was no difference between hemispheres at the source level either in coherence values for word or sentence processing or in evoked response to syllables. Results highlight the importance of the lower frequencies for speech tracking in the brain across different lexical units. Further, stimulus length affects the speech-brain associations suggesting methodological approaches should be selected carefully when studying speech envelope processing at the neural level. Speech tracking in the brain seems decoupled from more general maturation of the auditory cortex.

Neural Responses to Musical Rhythm in Chinese Children With Reading Difficulties.

The perception of the musical rhythm has been suggested as one of the predicting factors for reading abilities. Several studies have demonstrated that children with reading difficulties (RD) show reduced neural sensitivity in musical rhythm perception. Despite this prior evidence, the association between music and reading in Chinese is still controversial. In the present study, we sought to answer the question of whether the musical rhythm perception of Chinese children with RD is intact or not, providing further clues on how reading and music might be interlinked across languages. Oddball paradigm was adapted for testing the difference of musical rhythm perception, including predictable and unpredictable omission, in elementary school children with RD and typically developing age-controlled children with magnetoencephalography (MEG). We used the cluster-based permutation tests to examine the statistical difference in neural responses. The event-related field (ERF) components, mismatch negativity (MMNm) and P3a(m), were elicited by the rhythmical patterns with omitted strong beats. Specifically, differential P3a(m) components were found smaller in children with RD when comparing the rhythmical patterns between predictable and unpredicted omission patterns. The results showed that brain responses to the omission in the strong beat of an unpredicted rhythmic pattern were significantly smaller in Chinese children with RD. This indicated that children with RD may be impaired in the auditory sensitivity of rhythmic beats. This also suggests that children with reading difficulties may have atypical neural representations of rhythm that could be one of the underlying factors in dysfluent reading development.

Rapid changes in brain activity during learning of grapheme-phoneme associations in adults.

Learning to associate written letters with speech sounds is crucial for the initial phase of acquiring reading skills. However, little is known about the cortical reorganization for supporting letter-speech sound learning, particularly the brain dynamics during the learning of grapheme-phoneme associations. In the present study, we trained 30 Finnish participants (mean age: 24.33 years, SD: 3.50 years) to associate novel foreign letters with familiar Finnish speech sounds on two consecutive days (first day â€‹~ â€‹50 â€‹min; second day â€‹~ â€‹25 â€‹min), while neural activity was measured using magnetoencephalography (MEG). Two sets of audiovisual stimuli were used for the training in which the grapheme-phoneme association in one set (Learnable) could be learned based on the different learning cues provided, but not in the other set (Control). The learning progress was tracked at a trial-by-trial basis and used to segment different learning stages for the MEG source analysis. The learning-related changes were examined by comparing the brain responses to Learnable and Control uni/multi-sensory stimuli, as well as the brain responses to learning cues at different learning stages over the two days. We found dynamic changes in brain responses related to multi-sensory processing when grapheme-phoneme associations were learned. Further, changes were observed in the brain responses to the novel letters during the learning process. We also found that some of these learning effects were observed only after memory consolidation the following day. Overall, the learning process modulated the activity in a large network of brain regions, including the superior temporal cortex and the dorsal (parietal) pathway. Most interestingly, middle- and inferior-temporal regions were engaged during multi-sensory memory encoding after the cross-modal relationship was extracted from the learning cues. Our findings highlight the brain dynamics and plasticity related to the learning of letter-speech sound associations and provide a more refined model of grapheme-phoneme learning in reading acquisition.

Context-dependent minimisation of prediction errors involves temporal-frontal activation.

According to the predictive coding model of perception, the brain constantly generates predictions of the upcoming sensory inputs. Perception is realised through a hierarchical generative model which aims at minimising the discrepancy between predictions and the incoming sensory inputs (i.e., prediction errors). Notably, prediction errors are weighted depending on precision of prior information. However, it remains unclear whether and how the brain monitors prior precision when minimising prediction errors in different contexts. The current study used magnetoencephalography (MEG) to address this question. We presented participants with repetition of two non-predicted probes embedded in context of high and low precision, namely mispredicted and unpredicted probes. Non-parametric permutation statistics showed that the minimisation of precision-weighted prediction errors started to dissociate on early components of the auditory responses (including the P1m and N1m), indicating that the brain can differentiate between these scenarios at an early stage of the auditory processing stream. Permutation statistics conducted on the depth-weighted statistical parametric maps (dSPM) source solutions of the repetition difference waves between the two non-predicted probes further revealed a cluster extending from the frontal areas to the posterior temporal areas in the left hemisphere. Overall, the results suggested that context precision not only changes the weighting of prediction errors but also modulates the dynamics of how prediction errors are minimised upon the learning of statistical regularities (achieved by stimulus repetition), which likely involves differential activation at temporal-frontal regions.

Top-Down Predictions of Familiarity and Congruency in Audio-Visual Speech Perception at Neural Level.

During speech perception, listeners rely on multimodal input and make use of both auditory and visual information. When presented with speech, for example syllables, the differences in brain responses to distinct stimuli are not, however, caused merely by the acoustic or visual features of the stimuli. The congruency of the auditory and visual information and the familiarity of a syllable, that is, whether it appears in the listener's native language or not, also modulates brain responses. We investigated how the congruency and familiarity of the presented stimuli affect brain responses to audio-visual (AV) speech in 12 adult Finnish native speakers and 12 adult Chinese native speakers. They watched videos of a Chinese speaker pronouncing syllables (/pa/, /pha/, /ta/, /tha/, /fa/) during a magnetoencephalography (MEG) measurement where only /pa/ and /ta/ were part of Finnish phonology while all the stimuli were part of Chinese phonology. The stimuli were presented in audio-visual (congruent or incongruent), audio only, or visual only conditions. The brain responses were examined in five time-windows: 75-125, 150-200, 200-300, 300-400, and 400-600 ms. We found significant differences for the congruency comparison in the fourth time-window (300-400 ms) in both sensor and source level analysis. Larger responses were observed for the incongruent stimuli than for the congruent stimuli. For the familiarity comparisons no significant differences were found. The results are in line with earlier studies reporting on the modulation of brain responses for audio-visual congruency around 250-500 ms. This suggests a much stronger process for the general detection of a mismatch between predictions based on lip movements and the auditory signal than for the top-down modulation of brain responses based on phonological information.

Audiovisual Processing of Chinese Characters Elicits Suppression and Congruency Effects in MEG.

Learning to associate written letters/characters with speech sounds is crucial for reading acquisition. Most previous studies have focused on audiovisual integration in alphabetic languages. Less is known about logographic languages such as Chinese characters, which map onto mostly syllable-based morphemes in the spoken language. Here we investigated how long-term exposure to native language affects the underlying neural mechanisms of audiovisual integration in a logographic language using magnetoencephalography (MEG). MEG sensor and source data from 12 adult native Chinese speakers and a control group of 13 adult Finnish speakers were analyzed for audiovisual suppression (bimodal responses vs. sum of unimodal responses) and congruency (bimodal incongruent responses vs. bimodal congruent responses) effects. The suppressive integration effect was found in the left angular and supramarginal gyri (205-365 ms), left inferior frontal and left temporal cortices (575-800 ms) in the Chinese group. The Finnish group showed a distinct suppression effect only in the right parietal and occipital cortices at a relatively early time window (285-460 ms). The congruency effect was only observed in the Chinese group in left inferior frontal and superior temporal cortex in a late time window (about 500-800 ms) probably related to modulatory feedback from multi-sensory regions and semantic processing. The audiovisual integration in a logographic language showed a clear resemblance to that in alphabetic languages in the left superior temporal cortex, but with activation specific to the logographic stimuli observed in the left inferior frontal cortex. The current MEG study indicated that learning of logographic languages has a large impact on the audiovisual integration of written characters with some distinct features compared to previous results on alphabetic languages.

Aging-related changes of EEG synchronization during a visual working memory task.

Differences of EEG synchronization between normal old and young people during a working memory (WM) task were investigated. The synchronization likelihood (SL) is a novel method to assessed synchronization in multivariate time series for non-stationary systems. To evaluate this method to study the mechanisms of WM, we calculated the SL values in brain electrical activity for both resting state and task state. EEG signals were recorded from 14 young adults and 12 old adults during two different states, respectively. SL was used to measure EEG synchronization between 19 electrodes in delta, theta, alpha1, alpha2 and beta frequency bands. Bad task performance and significantly decreased EEG synchronization were found in old group compared to young group in alpha1, alpha2 and beta frequency bands during the WM task. Moreover, significantly decreased EEG synchronization in beta band in the elder was also detected during the resting state. The findings suggested that reduced EEG synchronization may be one of causes for WM capacity decline along with healthy aging.

Brain Responses to Letters and Speech Sounds and Their Correlations With Cognitive Skills Related to Reading in Children.

Letter-speech sound (LSS) integration is crucial for initial stages of reading acquisition. However, the relationship between cortical organization for supporting LSS integration, including unimodal and multimodal processes, and reading skills in early readers remains unclear. In the present study, we measured brain responses to Finnish letters and speech sounds from 29 typically developing Finnish children in a child-friendly audiovisual integration experiment using magnetoencephalography. Brain source activations in response to auditory, visual and audiovisual stimuli as well as audiovisual integration response were correlated with reading skills and cognitive skills predictive of reading development after controlling for the effect of age. Regression analysis showed that from the brain measures, the auditory late response around 400 ms showed the largest association with phonological processing and rapid automatized naming abilities. In addition, audiovisual integration effect was most pronounced in the left and right temporoparietal regions and the activities in several of these temporoparietal regions correlated with reading and writing skills. Our findings indicated the important role of temporoparietal regions in the early phase of learning to read and their unique contribution to reading skills.

Acupuncture for balance dysfunction in patients with stroke: A systematic review protocol.

BACKGROUND: Balance dysfunctions in stroke survivors are common and have significant impact on functional independence and rehabilitation. As a crucial technique of Traditional Chinese Medicine, acupuncture has been used widely for balance dysfunctions after stroke, although its effective evidence is not clear. Hence, we plan this systematic review protocol to evaluate the value of its efficacy and safety for balance dysfunctions after stroke. METHODS: We will search the databases from the publishment to April 2018: Web of Science, PubMed, Medline, Cochrane Library, EBASE, WHO International Clinical Trials Registry Platform, Wanfang, Chinese Biomedical Literature Database, Chinese Scientific Journal Database (VIP), and China National Knowledge Infrastructure. The clinical efficacy will be accepted as the primary outcomes. RevMan V.5.3 software will be used to compute the data synthesis when a meta-analysis is allowed. RESULTS: This systematic review and meta-analysis will provide a high-quality synthesis of current evidence of acupuncture for balance dysfunctions after stroke including clinical efficacy, balance ability, walking ability, and activity of daily life etcetera. CONCLUSION: This protocol will determine whether acupuncture is an effective and safety intervention for balance dysfunctions after stroke.

Salidroside alleviates cachexia symptoms in mouse models of cancer cachexia via activating mTOR signalling.

BACKGROUND: Cachexia has a devastating impact on survival and quality of life for many cancer patients and contributes to nearly one-third of all cancer deaths; also, it is associated with poor responses to chemotherapy and survival. A better understanding of the underlying mechanisms of cancer-associated cachexia (CAC), coupled with effective therapeutic approaches, will improve management of progressive functional impairment in cancer patients. Salidroside, a phenylpropanoid glycoside in Rhodiola rosea L, has been reported to possess potential anti-fatigue, anti-ageing, and anti-Alzheimer's disease properties. It is widely consumed as a nutritional supplement, but its effects on CAC and the possible mechanism remain a mystery. METHODS: In the murine models of cachexia induced by CT-26 and Lewis lung carcinoma (LLC) tumour, respectively, main features of CAC were determined after treatment of salidroside or chemotherapy. In vitro experiments were performed using murine C2C12 myotubes, which were treated by tumour necrosis factor-α. Levels of several critical muscle-related signal proteins such as mammalian target of rapamycin (mTOR), p-mTOR, and myosin heavy chain (MyHC) were examined using western blot both in vitro and in vivo. RESULTS: In the present study, we showed the exciting effect of salidroside on the treatment of CAC. In CT-26 and LLC models, respectively, salidroside treatment could effectively preserve the tumour-free body weight, decrease loss of adipose and gastrocnemius muscles, alleviate tumour burden, and prolong their survival time. Additionally, in combined chemotherapy, salidroside could synergistically enhance the anti-tumour activity of cisplatin, especially decreased or eliminated chemotherapy-induced cachexia. Further analysis demonstrated that salidroside could significantly increase expression of mTOR, p-mTOR, and MyHC in gastrocnemius muscle. Also, results in vitro showed that salidroside could not only obviously increase mTOR, p-mTOR, and MyHC expression in C2C12 myotubes but also effectively rescue their down-regulation induced by tumour necrosis factor-α. CONCLUSIONS: In the current study, the exciting effect of salidroside on CAC suggested that salidroside supplementation might be a promising approach for a multi-targeted therapy for the treatment of CAC.

Assay of melamine in milk products with a pH-mediated stacking technique in capillary electrophoresis.

A pH-mediated stacking method in capillary electrophoresis as an assay for low concentrations of melamine in milk products was established. Real samples were treated with acetone and sodium acetate and injected directly after centrifugation and filtration. Several experimental factors, such as buffer pH, buffer concentration, sample matrix, injection/sweeping ratio, sweeping time/voltages, separation voltages, as well as sample pretreatment, which affected stacking and separation, were investigated and optimized. Under the selected condition, a low LOD of 0.01 µmol/L (S/N = 5) and a wide range of linearity of 0.01∼1.0 µmol/L could be easily achieved with a good reproducibility (RSDs < 5.8% for both migration time and peak area) and an acceptable recovery of 94.0∼103.2% (for milk, infant formula, yogurt, and milk products). The proposed method was suitable for routine assay of melamine in real milk samples.

[Pathologic changes caused by highly pathogenic H5N1 avian influenza virus: postmortem study of a case].

OBJECTIVE: To report the postmortem findings of a case of highly pathogenic H5N1 avian influenza virus occurring in human beings. METHODS: Postmortem examination was carried out in a deceased caused by highly pathogenic H5N1 avian influenza virus. Detailed light microscopy of major organs, including heart, lungs, liver, spleen, kidneys and brain, was performed. The lung tissue was further investigated by histochemistry, immunohistochemistry and electron microscopy. RESULTS: Major histopathologic changes in lungs secondary to highly pathogenic H5N1 avian influenza virus included diffuse alveolar damage, hyaline membrane formation and focal hemorrhage. Some of the alveolar spaces contained lightly eosinophilic liquid, lymphocytes, macrophages, plasma cells and small number of neutrophils. Congested capillaries were commonly seen in the alveolar septa which were focally rimmed by hyaline membrane. Immunohistochemical study showed that the lymphocytes were mainly of T lineage and macrophages were also demonstrated. CONCLUSIONS: Highly pathogenic H5N1 avian influenza virus causes pathologic changes mostly in lungs, including diffuse alveolar damage and acute exudative changes (involving mainly T lymphocytes and macrophages). The resulting parenchymal destruction, consolidation, pulmonary edema and hemorrhage eventually lead to respiratory distress and death.