Effect of tempo on the age-related changes in temporal expectation driven by rhythms.

Temporal expectation refers to the capacity to allocate resources at a particular point in time, enabling us to enhance our behavior performance. Empirical evidence indicates that, among younger adults, temporal expectation can be driven by rhythm (i.e., regular sequences of stimuli). However, whether there are age-related changes in rhythm-based temporal expectation has not been clearly established. Furthermore, whether tempo can influence the relationship between rhythm-based temporal expectation and aging remains unexplored. To address these questions, both younger and older participants took part in a rhythm-based temporal expectation task, engaging three distinct tempos: 600 ms (fast), 1800 ms (moderate), or 3000 ms (slow). The results demonstrated that temporal expectation effects (i.e., participants exhibited significantly faster responses during the regular trials compared to the irregular trials) were observed in both the younger and older participants under the moderate tempo condition. However, in the fast and slow tempo conditions, the temporal expectation effects were solely observed in the younger participants. These findings revealed that rhythm-based temporal expectations can be preserved during aging but within a specific tempo range. When the tempo falls within the range of either being too fast or too slow, it can manifest age-related declines in temporal expectations driven by rhythms.

Audiovisual n-Back Training Alters the Neural Processes of Working Memory and Audiovisual Integration: Evidence of Changes in ERPs.

(1) Background: This study investigates whether audiovisual n-back training leads to training effects on working memory and transfer effects on perceptual processing. (2) Methods: Before and after training, the participants were tested using the audiovisual n-back task (1-, 2-, or 3-back), to detect training effects, and the audiovisual discrimination task, to detect transfer effects. (3) Results: For the training effect, the behavioral results show that training leads to greater accuracy and faster response times. Stronger training gains in accuracy and response time using 3- and 2-back tasks, compared to 1-back, were observed in the training group. Event-related potentials (ERPs) data revealed an enhancement of P300 in the frontal and central regions across all working memory levels after training. Training also led to the enhancement of N200 in the central region in the 3-back condition. For the transfer effect, greater audiovisual integration in the frontal and central regions during the post-test rather than pre-test was observed at an early stage (80-120 ms) in the training group. (4) Conclusion: Our findings provide evidence that audiovisual n-back training enhances neural processes underlying a working memory and demonstrate a positive influence of higher cognitive functions on lower cognitive functions.

Aging effect of cross-modal interactions during audiovisual detection and discrimination by behavior and ERPs.

Introduction: Numerous studies have shown that aging greatly affects audiovisual integration; however, it is still unclear when the aging effect occurs, and its neural mechanism has yet to be fully elucidated. Methods: We assessed the audiovisual integration (AVI) of older (n = 40) and younger (n = 45) adults using simple meaningless stimulus detection and discrimination tasks. The results showed that the response was significantly faster and more accurate for younger adults than for older adults in both the detection and discrimination tasks. The AVI was comparable for older and younger adults during stimulus detection (9.37% vs. 9.43%); however, the AVI was lower for older than for younger adults during stimulus discrimination (9.48% vs. 13.08%) behaviorally. The electroencephalography (EEG) analysis showed that comparable AVI amplitude was found at 220-240 ms for both groups during stimulus detection and discrimination, but there was no significant difference between brain regions for older adults but a higher AVI amplitude in the right posterior for younger adults. Additionally, a significant AVI was found for younger adults in 290-310 ms but was absent for older adults during stimulus discrimination. Furthermore, significant AVI was found in the left anterior and right anterior at 290-310 ms for older adults but in the central, right posterior and left posterior for younger adults. Discussion: These results suggested that the aging effect of AVI occurred in multiple stages, but the attenuated AVI mainly occurred in the later discriminating stage attributed to attention deficit.

Sustained visual attentional load modulates audiovisual integration in older and younger adults.

Previous studies have shown that attention influences audiovisual integration (AVI) in multiple stages, but it remains unclear how AVI interacts with attentional load. In addition, while aging has been associated with sensory-functional decline, little is known about how older individuals integrate cross-modal information under attentional load. To investigate these issues twenty older adults and 20 younger adults were recruited to conduct a dual task including a multiple object tracking (MOT) task, which manipulated sustained visual attentional load, and an audiovisual discrimination task, which assesses AVI. The results showed that response times were shorter and hit rate was higher for audiovisual stimuli than for auditory or visual stimuli alone and in younger adults than in older adults. The race model analysis showed that AVI was higher under the load_3 condition (monitoring two targets of the MOT task) than under any other load condition (no-load [NL], one or three targets monitoring). This effect was found regardless of age. However, AVI was lower in older adults than younger adults under NL condition. Moreover, the peak latency was longer, and the time window of AVI was delayed in older adults compared to younger adults under all conditions. These results suggest that slight visual sustained attentional load increased AVI but that heavy visual sustained attentional load decreased AVI, which supports the claim that attention resource was limited, and we further proposed that AVI was positively modulated by attentional resource. Finally, there were substantial impacts of aging on AVI; AVI was delayed in older adults.

Auditory attentional load modulates the temporal dynamics of audiovisual integration in older adults: An ERPs study.

As older adults experience degenerations in perceptual ability, it is important to gain perception from audiovisual integration. Due to attending to one or more auditory stimuli, performing other tasks is a common challenge for older adults in everyday life. Therefore, it is necessary to probe the effects of auditory attentional load on audiovisual integration in older adults. The present study used event-related potentials (ERPs) and a dual-task paradigm [Go / No-go task + rapid serial auditory presentation (RSAP) task] to investigate the temporal dynamics of audiovisual integration. Behavioral results showed that both older and younger adults responded faster and with higher accuracy to audiovisual stimuli than to either visual or auditory stimuli alone. ERPs revealed weaker audiovisual integration under the no-attentional auditory load condition at the earlier processing stages and, conversely, stronger integration in the late stages. Moreover, audiovisual integration was greater in older adults than in younger adults at the following time intervals: 60-90, 140-210, and 430-530 ms. Notably, only under the low load condition in the time interval of 140-210 ms, we did find that the audiovisual integration of older adults was significantly greater than that of younger adults. These results delineate the temporal dynamics of the interactions with auditory attentional load and audiovisual integration in aging, suggesting that modulation of auditory attentional load affects audiovisual integration, enhancing it in older adults.

Effect of aging on audiovisual integration: Comparison of high- and low-intensity conditions in a speech discrimination task.

Audiovisual integration is an essential process that influences speech perception in conversation. However, it is still debated whether older individuals benefit more from audiovisual integration than younger individuals. This ambiguity is likely due to stimulus features, such as stimulus intensity. The purpose of the current study was to explore the effect of aging on audiovisual integration, using event-related potentials (ERPs) at different stimulus intensities. The results showed greater audiovisual integration in older adults at 320-360 ms. Conversely, at 460-500 ms, older adults displayed attenuated audiovisual integration in the frontal, fronto-central, central, and centro-parietal regions compared to younger adults. In addition, we found older adults had greater audiovisual integration at 200-230 ms under the low-intensity condition compared to the high-intensity condition, suggesting inverse effectiveness occurred. However, inverse effectiveness was not found in younger adults. Taken together, the results suggested that there was age-related dissociation in audiovisual integration and inverse effectiveness, indicating that the neural mechanisms underlying audiovisual integration differed between older adults and younger adults.

Auditory attentional load attenuates age-related audiovisual integration: An EEG study.

Studies have revealed that visual attentional load modulated audiovisual integration (AVI) greatly; however, auditory and visual attentional resources are separate to some degree, and task-irrelevant auditory information could arouse much faster and larger attentional alerting effects than visible information. Here, we aimed to explore how auditory attentional load influences AVI and how aging could have an effect. Thirty older and 30 younger adults participated in an AV discrimination task with an additional auditory distractor competing for attentional resources. The race model analysis revealed highest AVI in the low auditory attentional load condition (low > no > medium > high, pairwise comparison, all p ≤ 0.047) for younger adults and a higher AVI under the no auditory attentional-load condition (p = 0.008), but there was a lower AVI under the low (p = 0.019), medium (p < 0.001), and high (p = 0.021) auditory attentional-load conditions for older adults than for younger adults. The time-frequency analysis revealed higher theta- and alpha-band AVI oscillation under no and low auditory attentional-load conditions than under medium and high auditory attentional-load conditions for both older (all p ≤ 0.011) and younger (all p ≤ 0.024) adults. Additionally, Weighted Phase lag index (WPLI) analysis revealed higher theta-band and lower alpha-band global functional connectivity for older adults during AV stimuli processing (all p ≤ 0.031). These results suggested that the AVI was higher in the low attentional-load condition than in the no attentional-load condition but decreased inversely with increasing of attentional load and that there was a significant aging effect in older adults. In addition, the strengthened theta-band global functional connectivity in older adults during AV stimuli processing might be an adaptive phenomenon for age-related perceptual decline.

De Novo Production of Plant 4'-Deoxyflavones Baicalein and Oroxylin A from Ethanol in Crabtree-Negative Yeast.

Baicalein and oroxylin A are well-known medicinal 4'-deoxyflavones found mainly in the roots of traditional medicinal plant Scutellaria baicalensis Georgi. However, extraction from plants is time-consuming, environmentally unfriendly, and insufficient. Although microbial synthesis of flavonoids has been extensively reported, synthesis of downstream modified 4'-deoxyflavones has not, and their yields are extremely low. Here, we reassembled the S. baicalensis 4'-deoxyflavone biosynthetic pathway in a Crabtree-negative yeast, Pichia pastoris, with activity analysis and combinatorial expression of eight biosynthetic genes, allowing production of 4'-deoxyflavones like baicalein, oroxylin A, wogonin, norwogonin, 6-methoxywogonin, and the novel 6-methoxynorwogonin. De novo baicalein synthesis was then achieved by complete pathway assembly. Toxic intermediates highly impaired the cell production capacity; hence, we alleviated cinnamic acid growth inhibition by culturing the cells at near-neutral pH and using alcoholic carbon sources. To achieve pathway balance and improve baicalein and oroxylin A synthesis, we further divided the pathway into five modules. A series of ethanol-induced and constitutive transcriptional amplification devices were constructed to adapt to the modules. This fine-tuning pathway control considerably reduced byproduct and intermediate accumulation and achieved high-level de novo baicalein (401.9 mg/L with a total increase of 1182-fold, the highest titer reported) and oroxylin A (339.5 mg/L, for the first time) production from ethanol. This study provides new strategies for the microbial synthesis of 4'-deoxyflavones and other flavonoids.

Audiovisual integration of the dynamic hand-held tool at different stimulus intensities in aging.

Introduction: In comparison to the audiovisual integration of younger adults, the same process appears more complex and unstable in older adults. Previous research has found that stimulus intensity is one of the most important factors influencing audiovisual integration. Methods: The present study compared differences in audiovisual integration between older and younger adults using dynamic hand-held tool stimuli, such as holding a hammer hitting the floor. Meanwhile, the effects of stimulus intensity on audiovisual integration were compared. The intensity of the visual and auditory stimuli was regulated by modulating the contrast level and sound pressure level. Results: Behavioral results showed that both older and younger adults responded faster and with higher hit rates to audiovisual stimuli than to visual and auditory stimuli. Further results of event-related potentials (ERPs) revealed that during the early stage of 60-100 ms, in the low-intensity condition, audiovisual integration of the anterior brain region was greater in older adults than in younger adults; however, in the high-intensity condition, audiovisual integration of the right hemisphere region was greater in younger adults than in older adults. Moreover, audiovisual integration was greater in the low-intensity condition than in the high-intensity condition in older adults during the 60-100 ms, 120-160 ms, and 220-260 ms periods, showing inverse effectiveness. However, there was no difference in the audiovisual integration of younger adults across different intensity conditions. Discussion: The results suggested that there was an age-related dissociation between high- and low-intensity conditions with audiovisual integration of the dynamic hand-held tool stimulus. Older adults showed greater audiovisual integration in the lower intensity condition, which may be due to the activation of compensatory mechanisms.

Minos and Restless transposon insertion mutagenesis of psychrotrophic fungus for red pigment synthesis adaptive to normal temperature.

The polar psychrotrophic fungus Geomyces sp. WNF-15A can produce high-quality natural red pigment for the potential use as edible pigment. However, it shows low-temperature-dependent synthesis of red pigment, which limits its large-scale industrial applications due to the difficult and high-cost bioprocess control. This study aims to develop transposon-mediated mutagenesis methods to generate mutants that are able to synthesize red pigment at normal temperature. Four transposable systems, including single and dual transposable systems, were established in this fungus based on the Minos from Drosophila hydei and the Restless from Tolypocladium inflatum. A total of 23 production-dominant mutants and 12 growth-dominant mutants were thus obtained by constructed transposable systems. At 14 °C and 20 °C, the MPS1 mutant strain achieved the highest level of red pigment (OD520 of 43.3 and 29.7, respectively), which was increased by 78.4% and 128.7% compared to the wild-type, respectively. Of note, 4 mutants (MPS1, MPS3, MPS4 and MPD1) successfully synthesized red pigment (OD520 of 5.0, 5.3, 4.7 and 4.9, respectively) at 25 °C, which broke the limit of the wild-type production under normal temperature. Generally, the dual transposable systems of Minos and Restless were more efficient than their single transposable systems for mutagenesis in this fungus. However, the positive mutation ratios were similar between the dual and single transposable systems for either Minos or Restless. This study provides alternative tools for genetic mutagenesis breeding of fungi from extreme environments.

Effect of Tempo on Temporal Expectation Driven by Rhythms in Dual-Task Performance.

Temporal expectation is the ability to focus attention at a particular moment in time to optimize performance, which has been shown to be driven by regular rhythms. However, whether the rhythm-based temporal expectations rely upon automatic processing or require the involvement of controlled processing has not been clearly established. Furthermore, whether the mechanism is affected by tempo remains unknown. To investigate this research question, the present study used a dual-task procedure. In a single task, the participants were instructed to respond to a visual target preceded by a regular or an irregular visual rhythm under a fast (500 ms) or slow (3,500 ms) tempo. The dual-task simultaneously combined a working memory (WM) task. The results showed temporal expectation effects in which the participants responded faster to the regular than to the irregular conditions in a single task. Moreover, this effect persisted under dual-task interference in the fast tempo condition but was impaired in the slow tempo condition. These results revealed that rhythmic temporal expectation induced by fast tempo was dependent on automatic processing. However, compared with the faster tempo, temporal expectation driven by a slower tempo might involve more controlled processing.

Visual Perceptual Load Attenuates Age-Related Audiovisual Integration in an Audiovisual Discrimination Task.

Previous studies confirmed that the cognitive resources are limited for each person, and perceptual load affects the detection of stimulus greatly; however, how the visual perceptual load influences audiovisual integration (AVI) is still unclear. Here, 20 older and 20 younger adults were recruited to perform an auditory/visual discrimination task under various visual perceptual-load conditions. The analysis for the response times revealed a significantly faster response to the audiovisual stimulus than to the visual stimulus or auditory stimulus (all p < 0.001), and a significantly slower response by the older adults than by the younger adults to all targets (all p ≤ 0.024). The race-model analysis revealed a higher AV facilitation effect for older (12.54%) than for younger (7.08%) adults under low visual perceptual-load conditions; however, no obvious difference was found between younger (2.92%) and older (3.06%) adults under medium visual perceptual-load conditions. Only the AV depression effect was found for both younger and older adults under high visual perceptual-load conditions. Additionally, the peak latencies of AVI were significantly delayed in older adults under all visual perceptual-load conditions. These results suggested that visual perceptual load decreased AVI (i.e., depression effects), and the AVI effect was increased but delayed for older adults.

High-level living cell production of cytidine-5'-diphosphocholine in metabolically engineered yeast.

Industrial production of neuroprotective drug CDP-choline is accomplished via permeabilized or lysed cell biotransformation because of the inefficient penetration of substrates into intact cells. We previously proposed a novel one-step living cell method for CDP-choline production by engineered yeast, but obtained low titer and molar yield. This study develops a high-production strain with improved molar yield by metabolic engineering strategies. The selective markers previously integrated into host cell were recovered for facilitating genetic modification, which however resulted a strain with improved CDP-choline titer and molar yield to CMP. Knockout of 5'-NT or CDA in CMP sinking pathway but not APY in CTP sinking pathway further improved CDP-choline titer and molar yield to CMP. However, overexpression of seven enzymes in CTP synthetic pathway showed no positive functions. Finally, optimization of CMP and choline phosphate levels for the optimized recombinant strains achieved a high-level CDP-choline of ~30 g/L, which was enhanced by 400% compared to the previous work. Also, the molar yield of CDP-choline to CMP increased from 40% to 84.7%. The titer and molar yield are comparable to the reported permeabilized or lysed cell based biotransformation methods. It represents a novel and competitive paradigm for the potential industrial production of CDP-choline.

Sustained Auditory Attentional Load Decreases Audiovisual Integration in Older and Younger Adults.

The modulation of attentional load on the perception of auditory and visual information has been widely reported; however, whether attentional load alters audiovisual integration (AVI) has seldom been investigated. Here, to explore the effect of sustained auditory attentional load on AVI and the effects of aging, nineteen older and 20 younger adults performed an AV discrimination task with a rapid serial auditory presentation task competing for attentional resources. The results showed that responses to audiovisual stimuli were significantly faster than those to auditory and visual stimuli (AV > V ≥ A, all p < 0.001), and the younger adults were significantly faster than the older adults under all attentional load conditions (all p < 0.001). The analysis of the race model showed that AVI was decreased and delayed with the addition of auditory sustained attention (no_load > load_1 > load_2 > load_3 > load_4) for both older and younger adults. In addition, AVI was lower and more delayed in older adults than in younger adults in all attentional load conditions. These results suggested that auditory sustained attentional load decreased AVI and that AVI was reduced in older adults.

The Modulation of Exogenous Attention on Emotional Audiovisual Integration.

Although emotional audiovisual integration has been investigated previously, whether emotional audiovisual integration is affected by the spatial allocation of visual attention is currently unknown. To examine this question, a variant of the exogenous spatial cueing paradigm was adopted, in which stimuli varying by facial expressions and nonverbal affective prosody were used to express six basic emotions (happiness, anger, disgust, sadness, fear, surprise) via a visual, an auditory, or an audiovisual modality. The emotional stimuli were preceded by an unpredictive cue that was used to attract participants' visual attention. The results showed significantly higher accuracy and quicker response times in response to bimodal audiovisual stimuli than to unimodal visual or auditory stimuli for emotional perception under both valid and invalid cue conditions. The auditory facilitation effect was stronger than the visual facilitation effect under exogenous attention for the six emotions tested. Larger auditory enhancement was induced when the target was presented at the expected location than at the unexpected location. For emotional perception, happiness shared the biggest auditory enhancement among all six emotions. However, the influence of exogenous cueing effect on emotional perception seemed to be absent.

Exogenous Bimodal Cues Attenuate Age-Related Audiovisual Integration.

Previous studies have demonstrated that exogenous attention decreases audiovisual integration (AVI); however, whether the AVI is different when exogenous attention is elicited by bimodal and unimodal cues and its aging effect remain unclear. To clarify this matter, 20 older adults and 20 younger adults were recruited to conduct an auditory/visual discrimination task following bimodal audiovisual cues or unimodal auditory/visual cues. The results showed that the response to all stimulus types was faster in younger adults compared with older adults, and the response was faster when responding to audiovisual stimuli compared with auditory or visual stimuli. Analysis using the race model revealed that the AVI was lower in the exogenous-cue conditions compared with the no-cue condition for both older and younger adults. The AVI was observed in all exogenous-cue conditions for the younger adults (visual cue > auditory cue > audiovisual cue); however, for older adults, the AVI was only found in the visual-cue condition. In addition, the AVI was lower in older adults compared to younger adults under no- and visual-cue conditions. These results suggested that exogenous attention decreased the AVI, and the AVI was lower in exogenous attention elicited by bimodal-cue than by unimodal-cue conditions. In addition, the AVI was reduced for older adults compared with younger adults under exogenous attention.

Changes in efficiencies and interactions of attentional networks in Parkinson's disease with sleep disturbance.

Attention is composed of three distinct attentional networks: alerting, orienting, and executive control. Previous studies have confirmed that Parkinson's disease (PD) is associated with executive control deficits; however, the interactions among the three attentional networks and the influence of sleep disturbance in PD patients have not been investigated. Herein, the efficiencies for the three attentional networks and their interactions were evaluated using the revised attention network test. The results showed a significantly slower response and lower accuracy in the PD group than in the normal control group and a significantly slower response and lower accuracy in PD patients with sleep disturbance (PDS) than in PD patients without sleep disturbance (PDnS), which indicates a response deficit in PD and worsening in PDS. Additionally, the executive control efficiency was reduced in both PDS and PDnS, and significantly higher alerting efficiency and lower orienting efficiency were found in PDS. Furthermore, largely changed interactions and correlation patterns of attentional networks were found in PDS but not in PDnS. These results suggested that attentional networks were impaired in PD patients, particularly in those affected by sleep disturbances, and that PDS might establish special connections between attentional networks to compensate for cognitive dysfunction.

Alterations in the gut microbiota and metabolite profiles in the context of neuropathic pain.

The aim of this study was to explore the relationships among gut microbiota disturbances and serum and spinal cord metabolic disorders in neuropathic pain. 16S rDNA amplicon sequencing and serum and spinal cord metabolomics were used to identify alterations in the microbiota and metabolite profiles in the sham rats and the chronic constriction injury (CCI) model rats. Correlations between the abundances of gut microbiota components at the genus level, the levels of serum metabolites, and pain-related behavioural parameters were analysed. Ingenuity pathway analysis (IPA) was applied to analyse the interaction networks of the differentially expressed serum metabolites. First, we found that the composition of the gut microbiota was different between rats with CCI-induced neuropathic pain and sham controls. At the genus level, the abundances of Helicobacter, Phascolarctobacterium, Christensenella, Blautia, Streptococcus, Rothia and Lactobacillus were significantly increased, whereas the abundances of Ignatzschineria, Butyricimonas, Escherichia, AF12, and Corynebacterium were significantly decreased. Additionally, 72 significantly differentially expressed serum metabolites and 17 significantly differentially expressed spinal cord metabolites were identified between the CCI rats and the sham rats. Finally, correlation analysis showed that changes in the gut microbiota was significantly correlated with changes in serum metabolite levels, suggesting that dysbiosis of the gut microbiota is an important factor in modulating metabolic disturbances in the context of neuropathic pain. In conclusion, our research provides a novel perspective on the potential roles of the gut microbiota and related metabolites in neuropathic pain.

Effects of stimulus intensity on audiovisual integration in aging across the temporal dynamics of processing.

Previous studies have drawn different conclusions about whether older adults benefit more from audiovisual integration, and such conflicts may have been due to the stimulus features investigated in those studies, such as stimulus intensity. In the current study, using ERPs, we compared the effects of stimulus intensity on audiovisual integration between young adults and older adults. The results showed that inverse effectiveness, which depicts a phenomenon that lowing the effectiveness of sensory stimuli increases benefits of multisensory integration, was observed in young adults at earlier processing stages but was absent in older adults. Moreover, at the earlier processing stages (60-90 ms and 110-140 ms), older adults exhibited significantly greater audiovisual integration than young adults (all ps < 0.05). However, at the later processing stages (220-250 ms and 340-370 ms), young adults exhibited significantly greater audiovisual integration than old adults (all ps < 0.001). The results suggested that there is an age-related dissociation between early integration and late integration, which indicates that there are different audiovisual processing mechanisms in play between older adults and young adults.