Effects Of Stimuli Research Articles

Krill oil supplementation in vivo promotes increased fuel metabolism and protein synthesis in cultured human skeletal muscle cells

IntroductionKrill oil is a dietary supplement derived from Antarctic krill; a small crustacean found in the ocean. Krill oil is a rich source of omega-3 fatty acids, specifically eicosapentaenoic acid and docosahexaenoic acid, as well as the antioxidant astaxanthin. The aim of this study was to investigate the effects of krill oil supplementation, compared to placebo oil (high oleic sunflower oil added astaxanthin), in vivo on energy metabolism and substrate turnover in human skeletal muscle cells.MethodsSkeletal muscle cells (myotubes) were obtained before and after a 7-week krill oil or placebo oil intervention, and glucose and oleic acid metabolism and leucine accumulation, as well as effects of different stimuli in vitro, were studied in the myotubes. The functional data were combined with proteomic and transcriptomic analyses.ResultsIn vivo intervention with krill oil increased oleic acid oxidation and leucine accumulation in skeletal muscle cells, however no effects were observed on glucose metabolism. The krill oil-intervention-induced increase in oleic acid oxidation correlated negatively with changes in serum low-density lipoprotein (LDL) concentration. In addition, myotubes were also exposed to krill oil in vitro. The in vitro study revealed that 24 h of krill oil treatment increased both glucose and oleic acid metabolism in myotubes, enhancing energy substrate utilization. Transcriptomic analysis comparing myotubes obtained before and after krill oil supplementation identified differentially expressed genes associated with e.g., glycolysis/gluconeogenesis, metabolic pathways and calcium signaling pathway, while proteomic analysis demonstrated upregulation of e.g., LDL-receptor in myotubes obtained after the krill oil intervention.ConclusionThese findings suggest that krill oil intervention promotes increased fuel metabolism and protein synthesis in human skeletal muscle cells, with potential implications for metabolic health.

High chloride induces aldosterone resistance in the distal nephron.

Increasing the dietary intake of K+ in the setting of a high salt intake promotes renal Na+ excretion even though K+ concurrently enhances the secretion of aldosterone, the most effective stimulus for renal Na+ reabsorption. Here, we questioned whether in the high salt state a mechanism exists, which attenuates the aldosterone response to prevent renal Na+ reabsorption after high K+ intake. Mice were fed diets containing varying amounts of Na+ combined with KCl or KCitrate. Murine cortical connecting duct (mCCDcl1) cells were cultured in media containing normal or high [Cl-]. The response to aldosterone was analyzed by high-resolution imaging and by biochemical approaches. The canonical cellular response to aldosterone, encompassing translocation of the mineralocorticoid receptor (MR) and activation of the epithelial Na+ channel ENaC was repressed in Na+-replete mice fed a high KCl diet, even though plasma aldosterone concentrations were increased. The response to aldosterone was restored in Na+-replete mice when the extracellular [Cl-] increase was prevented by feeding a high KCitrate diet. In mCCDcl1 cells, an elevated extracellular [Cl-] was sufficient to disrupt the aldosterone-induced MR translocation. These findings indicate a pivotal role for extracellular [Cl-] in modulating renal aldosterone signaling to adapt MR activation by a high K+ intake to the NaCl balance. An impairment of [Cl-]-mediated aldosterone resistance may contribute to excessive MR activation by aldosterone in the presence of a high salt intake characteristic of the Western diet, resulting in an inappropriate salt reabsorption and its downstream detrimental effects.

Vibration-based mitigation of noxious-evoked responses to skin puncture in neonates and infants: a randomised controlled trial

ObjectiveTo assess the effect of a non-noxious vibratory stimulus on noxious-evoked cortical responses to skin puncture and to determine whether the presence of certain behavioural components may be used to...

Boostering motor imagery processing to improve gait in patients with Parkinson disease and freezing of gait: A pilot study

BackgroundGiven that patients with Parkinson's Disease (PD) and Freezing of Gait (FoG) may lack the cognitive resources necessary to activate the motor imagery (MI) process, investigating how to boost MI vividness and accuracy could be a valuable therapeutic strategy in MI Practice (MIP). ObjectiveWe aim to evaluate the priming effect of visual, or auditory, or attentional stimuli in enhancing MI ability by using quantitative data on gait and turning performance. MethodsNineteen PD participants with FoG underwent four one-week sessions of MIP, with pre and post clinical assessments. Each session included MI alone or one of three booster MI tasks (Attentional, Action observation, or Auditory) before imagining and executing walking straight and performing a 180° turn. Gait and turning performances were evaluated using six inertial sensors before and after each session. ResultsOur findings showed that both MI and boosted MI induced similar improvement in gait (speed and stride length) and 180° (step number and velocity) and 360° turning (velocity, angle) parameters compared to baseline. When differences among “booster” tasks were analyzed, results showed that Auditory and Attentional boosted MI were superior to MI alone in some gait and turning parameters. At the end of the 4 sessions, MI ability measured by means of Kinesthetic and Visual Imagery Questionnaire and Gait Imagery Questionnaire and FoG symptoms were also improved. ConclusionOur preliminary results suggest that boosting MI is a feasible strategy for enhancing MI ability and addressing FoG symptoms. Auditory and Attentional conditions appear to enhance the priming effect of MI on gait and turning performance more effectively.

Assessing the Effectiveness of Audio-Visual vs. Visual Neurofeedback for Attention Enhancement: A Pilot Study with Neurological, Behavioural, and Neuropsychological Measures.

Electroencephalogram (EEG) based Neurofeedback training has gained traction as a practical method for enhancing executive functions, particularly attention, among healthy individuals. The neurofeedback protocols based on EEG channel locations, frequency bands, or EEG features has been tested. However, the improvement in attention was not measured by comparing different feedback stimulus types. We believe that multisensory nature feedback even with few training sessions may induce strong effect. Therefore, this study compares the effect of audio-visual and visual feedback stimuli for attention enhancement utilizing neurophysiological, behavioural and neuropsychological measures. Total 21 subjects were recruited, undergoing six alternate days of neurofeedback training sessions to upregulate EEG beta power of frontocentral (FC5). Dwell time, fractional occupancy and transition probability were also estimated from the EEG beta power. Audiovisual group (G1) as compared to visual group (G2) demonstrate a significant increase of global EEG beta activity alongside improved dwell time (t = 2.76, p = 0.003), fractional occupancy (t = 1.73, p = 0.042) and transition probability (t = 2.46, p = 0.008) over the course of six neurofeedback training sessions. Similarly, the group (G1) shows higher scores (t = 2.13, p = 0.032) and faster reaction times (t = 2.22, p = 0.028) in Stroop task, along with increased score in Mindfulness Attention Awareness Scale (MAAS-15) questionnaire (t = 2.306, p = 0.012). Audiovisual neurofeedback may enhance training effectiveness, potentially achieving the same outcomes in fewer sessions compared to visual-only feedback. However, sufficient training days are essential for effect consolidation. This highlights the feasibility of completing neurofeedback training, a significant challenge in practice.

Effects of unconscious tactile stimuli on autonomic nervous activity and afferent signal processing

Autonomic nervous system (ANS) is a mechanism that regulates our internal environment. In recent years, the interest in how tactile stimuli presented directly to the body affect ANS function and cortical processing in humans has been renewed. However, it is not yet clear how subtle tactile stimuli below the level of consciousness affect human heart rate and cortical processing. To examine this, subthreshold electrical stimuli were presented to the left forearm of 43 participants during an image-viewing task, and electrocardiogram (ECG) and electroencephalogram (EEG) data were collected. The changes in the R-wave interval of the ECG immediately after the subthreshold electrical presentation and heartbeat-evoked potential (HEP), the afferent signal processing of cardiac activity, were measured. The results showed that heart rate decelerated immediately after the presentation of subthreshold electrical stimuli. The HEP during stimulus presentation was amplified for participants with greater heart rate acceleration immediately after this deceleration. The magnitude of these effects depended on the type of the subthreshold tactile stimuli. The results suggest that even with subthreshold stimulation, the changes in autonomic activity associated with orienting response and related afferent signal processing differ depending on the clarity of the tactile stimuli.

Single-cell transcriptomic atlas of enteroendocrine cells along the murine gastrointestinal tract.

Enteroendocrine cells (EECs) produce over 20 gut hormones which contribute to intestinal physiology, nutrient metabolism and the regulation of food intake. The objective of this study was to generate a comprehensive transcriptomic map of mouse EECs from the stomach to the rectum. EECs were purified by flow-cytometry from the stomach, upper small intestine, lower small intestine, caecum and large intestine of NeuroD1-Cre mice, and analysed by single cell RNA sequencing. Regional datasets were analysed bioinformatically and combined into a large cluster map. Findings were validated by L-cell calcium imaging and measurements of CCK secretion in vitro. 20,006 EECs across the full gastrointestinal tract could be subdivided based on their full transcriptome into 10 major clusters, each exhibiting a different pattern of gut hormone expression. EECs from the stomach were largely distinct from those found more distally, even when expressing the same hormone. Cell clustering was also observed when performed only using genes related to GPCR cell signalling, revealing GPCRs predominating in different EEC populations. Mc4r was expressed in 55% of Cck-expressing cells in the upper small intestine, where MC4R agonism was found to stimulate CCK release in primary cultures. Many individual EECs expressed more than one hormone as well as machinery for activation by multiple nutrients, which was supported by the finding that the majority of L-cells exhibited calcium responses to multiple stimuli. This comprehensive transcriptomic map of mouse EECs reveals patterns of GPCR and hormone co-expression that should be helpful in predicting the effects of nutritional and pharmacological stimuli on EECs from different regions of the gut. The finding that MC4R agonism stimulates CCK secretion adds to our understanding of the melanocortin system.

Longitudinal single-subject neuroimaging study reveals effects of daily environmental, physiological, and lifestyle factors on functional brain connectivity.

Our behavior and mental states are constantly shaped by our environment and experiences. However, little is known about the response of brain functional connectivity to environmental, physiological, and behavioral changes on different timescales, from days to months. This gives rise to an urgent need for longitudinal studies that collect high-frequency data. To this end, for a single subject, we collected 133 days of behavioral data with smartphones and wearables and performed 30 functional magnetic resonance imaging (fMRI) scans measuring attention, memory, resting state, and the effects of naturalistic stimuli. We find traces of past behavior and physiology in brain connectivity that extend up as far as 15 days. While sleep and physical activity relate to brain connectivity during cognitively demanding tasks, heart rate variability and respiration rate are more relevant for resting-state connectivity and movie-watching. This unique data set is openly accessible, offering an exceptional opportunity for further discoveries. Our results demonstrate that we should not study brain connectivity in isolation, but rather acknowledge its interdependence with the dynamics of the environment, changes in lifestyle, and short-term fluctuations such as transient illnesses or restless sleep. These results reflect a prolonged and sustained relationship between external factors and neural processes. Overall, precision mapping designs such as the one employed here can help to better understand intraindividual variability, which may explain some of the observed heterogeneity in fMRI findings. The integration of brain connectivity, physiology data and environmental cues will propel future environmental neuroscience research and support precision healthcare.

Concurrent perception of competing predictions: A "split-stimulus effect".

Visual illusions are systematic misperceptions that can help us glean the heuristics with which the brain constructs visual experience. In a recently discovered visual illusion (the "frame effect"), it has been shown that flashing a stimulus inside of a moving frame produces a large misperception of that stimulus's position. Across two experiments, we investigated a novel illusion (the "split stimulus effect") where the symmetrical motion of two overlaid frames produces two simultaneous positional misperceptions of a single stimulus. That is, one stimulus is presented but two are perceived. In both experiments, a single red dot was flashed when the moving frames reversed direction, and participants were asked to report how many dots they saw. Naïve participants sometimes reported seeing two dots when only one was presented, indicating spontaneous perception of the illusion. A Bayesian analysis of the population prevalence of this effect was conducted. The dependence of this effect on the frames' speed, the dot's opacity, spatial attention, as the presence/absence of pre-flash motion ("postdiction") was also investigated, and the features of this illusion were compared to similar motion position illusions within a predictive processing framework. In demonstrating this illusory "splitting" effect, this study is the first to show that it is possible to be simultaneously aware of two opposing perceptual predictions about a single object and provides evidence of the hyperpriors that limit and inform the structure of visual experience.

Evaluating the Effects of Compound Stimuli on Stimulus Control during Match-to-Sample Procedures

Evaluating the Effects of Compound Stimuli on Stimulus Control during Match-to-Sample Procedures

Effect of negative emotional stimuli on working memory: Impact of voluntary and automatic attention.

Emotions are known to influence cognitive performance, particularly working memory (WM) in both its aspects, processing, and maintenance. One explanatory mechanism might be that negative stimuli capture attentional resources, leaving fewer resources for attentional maintenance and processing of information in WM. However, this attentional capture was only investigated using WM tasks in which participants were explicitly asked to process negative items. The aim of this paper was to determine whether explicit processing of emotional stimuli is necessary to impair WM performance, or if their mere presence is enough to capture attention. For this purpose, participants performed a complex span task in which they alternated between memorizing a series of neutral words and processing either emotional images or neutral ones. In Experiment 1, participants were instructed to explicitly process emotional images, whereas in Experiment 2, emotional images were presented without any processing being required. In both experiments, we observed a decrease in memory performance when the images were negative compared to neutral. Whether or not voluntary processing is involved, emotional images seem to capture attentional resources, which in turn leads to a decline in memory performance. These results were discussed in relation to attentional theories and the influence of emotion on the specific mechanisms of WM.

Understanding responses of people with ASD in diverse reasoning tasks: A formal study.

Recent studies have shown that in some reasoning tasks people with Autism Spectrum Disorder perform better than typically developing people. This paper compares four such tasks, namely a syllogistic task, two decision-making tasks, and a task from the heuristics and biases literature, the aim being to identify common structure as well as differences. In the terminology of David Marr's three levels of cognitive systems, the tasks show commonalities on the computational level in terms of the effect of contextual stimuli, though an in-depth analysis of such contexts provides certain distinguishing features in the algorithmic level. We also make some general remarks on our approach, so as to set the stage for further studies in the area which could provide a better understanding of the reasoning process of ASD individuals.

Enhanced multisensory gain in older adults may be a by-product of inverse effectiveness: Evidence from a speeded response-time task.

Older adults experience a greater benefit from multisensory integration than their younger counterparts, but it is unclear why. One hypothesis is that age-related sensory decline weakens unisensory stimulus effectiveness, causing a boost in multisensory gain through inverse effectiveness. Many previous studies present stimuli at the same intensity for both younger and older adults (i.e., stimulus-matched), as opposed to accounting for each participant's unique perceptual ability (i.e., perception-matched). This makes it difficult to discern the source of age-related differences in multisensory gain. As such, we used two experiments to examine whether sensory decline is contributing to age-related differences in multisensory gain. In the first, we presented auditory (pure tones in noise), visual (Gabor patches in noise), and audiovisual stimuli and recorded response times from 31 younger (18-25) and 30 older (55-80) adults. Importantly, all participants were given identical stimuli, with the expectation that older adults would show worse unisensory performance, inducing inverse effectiveness. The second task was identical (younger N = 31, older N = 34), except stimuli were presented at each participant's 50% detection threshold, identified with an adaptive psychophysical staircase, controlling for any influence of inverse effectiveness. Older adults were found to exhibit greater multisensory gain (as measured by race model violations) on stimulus- but not perception-matched tasks, thus aligning with the principle of inverse effectiveness. That is, when accounting for potential age-related differences in perceptual abilities, older adults no longer experienced greater benefit from multisensory integration. These two experiments together suggest that the age-related increases in multisensory integration previously reported may be in part due to age-related declines in vision and audition. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Concentrated Growth Factor (CGF): A Potential New Player in Periodontal Regeneration

Regenerative procedures have become a key focus in contemporary rehabilitation therapies. In dentistry, research on growth factors for bone regeneration has identified autologous growth factors as the most effective stimuli for tissue regeneration and healing. These bioactive proteins play a crucial role in wound healing. Concentrated growth factor (CGF) is a recent advancement in 2 nd generation platelet concentrates. The use of different centrifugation speeds helps to obtain a significantly dense fibrin. Also, it contains more amount of growth factors than the other platelet concentrates available.

Preclinical evaluation of abuse potential of the peripherally-restricted kappa opioid receptor agonist HSK21542

HSK21542 is a peripherally-restricted kappa opioid receptor (KOR) agonist developed for pain treatment. Because of the CNS pharmacological concern of opioid receptor activation, such as physical dependence and addiction potential, an assessment of abuse potential of HSK21542 was required prior to marketing approval. The preclinical abuse potential assessments for HSK21542 included the following studies: 1) intravenous self-administration study to explore the relative reinforcing efficacy in rats self-administering remifentanil; 2) rat drug discrimination study to examine the pharmacological similarity of the interoceptive or subjective effects of HSK21542 in rats discriminating pentazocine; 3) rat conditioned place preference (CPP) paradigm to test the rewarding effects; 4) rat natural physical dependence-spontaneous withdrawal study in rats chronically treated with HSK21542; 5) naloxone-precipitated withdrawal assay following chronic HSK21542 exposure to evaluate its physical dependence potential. The results showed that HSK21542 was devoid of behavioral evidence of positive reinforcing effect and did not share similar discriminative stimulus effects with pentazocine. HSK21542 also did not produce CPP in rats. In addition, HSK21542 did not produce spontaneous withdrawal or naloxone-precipitated withdrawal in rats with chronic treatments. Collectively, these preclinical findings suggest that HSK21542 has no abuse potential in animals, which demonstrate low abuse potential in humans.

Relationship between Sensory Processing Sensitivity and Personality Traits

Reactions to stimuli vary from person to person. The same stimulus has different effects depending on the perception of different people and the physical and mental states they are in. Considering this difference, situations can be seen in which a person perceives a specific stimulus or group of stimuli as negative and disturbing for themselves. In particular, people with high levels of sensory processing sensitivity feel the negative effects of stimuli more intensely both in terms of their internal processes (hunger, pain, sadness, stress, etc.) and the situation of the physical environment (loud noise, bright light, pungent odor, etc.) which they are in. On the other hand, the existence of situations where sensory processing sensitivity has a positive effect is also noticeable. In this context, the relationship between sensory processing sensitivity and personality traits is examined. The concept of personality is explained in different ways by many different theorists in the international literature. In order to avoid confusion that may arise in the definition and understanding of personality traits, in this review study, personality traits are examined on the basis of the Five Factor Personality Theory. Within the framework of the personality definition of the Five Factor Personality Theory, The relationship between five basic personality traits and sensory processing sensitivity is examined by also considering the subdimensions of each five personality traits.

A Comparison of Ocular Vestibular Evoked Myogenic Potentials via Audiometric and Nonaudiometric Bone Vibrators.

There is limited evidence demonstrating the ability of audiometric bone vibrators to elicit ocular vestibular evoked myogenic potentials (oVEMPs). The RadioEar B71 bone vibrator has insufficient power output to reliably evoke oVEMPs, which has previously left nonaudiometric and nonmedically approved devices such as the Brüel & Kjær Mini-shaker 4810 as the only feasible alternative. The newer RadioEar B81 model has a higher power output than its predecessor, but evidence for its suitability for eliciting oVEMPs has so far been mixed. This variability may be due to factors other than simply the power output, such as whether sufficient static force is applied to hold the transducer in place and transfer vibratory energy into the bone. This study aimed to test the hypothesis that bone-conducted oVEMPs can be obtained with the B81 that are equivalent to those from the Mini-shaker, the de facto gold-standard transducer for this response, when the outputs of the two transducers are matched and they are coupled with sufficient static force. oVEMPs elicited by both transducers were recorded in a counterbalanced within-groups design. Sixteen healthy adults (12 female; 22-47 years) with no history of hearing, balance, or neurological disorders were included in the study. One-cycle alternating tone-burst stimuli at 500 Hz were delivered to the mastoid from each transducer. The vibratory force levels were matched at 127 dB peak-to-peak equivalent force levels, and both were held in place with a static force around 10 N. oVEMP waveforms were gathered from the contralateral eye using the belly-tendon montage and were assessed for statistical equivalence. There was an absence of any statistically significant difference in N10 and N10-P15 amplitudes in oVEMPs from each transducer. Our results indicate that B81 can elicit oVEMPs with no meaningful differences to those from the Mini-shaker, provided effective stimulus levels are matched and static force is sufficient. Although further work is necessary to investigate equivalence at other stimulus frequencies and stimulation sites, the results support the use of the B81 to elicit 500Hz oVEMPs at the mastoid in a clinical setting.

Combined Effects of Cyclic Hypoxic and Mechanical Stimuli on Human Bone Marrow Mesenchymal Stem Cell Differentiation: A New Approach to the Treatment of Bone Loss.

Background: The prevention and treatment of bone loss and osteoporotic fractures is a public health challenge. Combined with normobaric hypoxia, whole-body vibration has a high clinic potential in bone health and body composition. The effect of this therapy may be mediated by its action on bone marrow mesenchymal stem cells (MSCs). Objectives: Evaluate the effects of cyclic low-vibration stimuli and/or hypoxia on bone marrow-derived human MSC differentiation. Methods: MSCs were exposed four days per week, two hours/day, to hypoxia (3% O2) and/or vibration before they were induced to differentiate or during differentiation into osteoblasts or adipocytes. Gene and protein expression of osteoblastic, adipogenic, and cytoskeletal markers were studied, as well as extracellular matrix mineralization and lipid accumulation. Results: early osteoblastic markers increased in undifferentiated MSCs, pretreated in hypoxia and vibration. This pretreatment also increased mRNA levels of osteoblastic genes and beta-catenin protein in the early stages of differentiation into osteoblasts without increasing mineralization. When MSCs were exposed to vibration under hypoxia or normoxia during osteoblastic differentiation, mineralization increased with respect to cultures without vibrational stimuli. In MSCs differentiated into adipocytes, both in those pretreated as well as exposed to different conditions during differentiation, lipid formation decreased. Changes in adipogenic gene expression and increased beta-catenin protein were observed in cultures treated during differentiation. Conclusions: Exposure to cyclic hypoxia in combination with low-intensity vibratory stimuli had positive effects on osteoblastic differentiation and negative ones on adipogenesis of bone marrow-derived MSCs. These results suggest that in elderly or frail people with difficulty performing physical activity, exposure to normobaric cyclic hypoxia and low-density vibratory stimuli could improve bone metabolism and health.

Static magnetic field contributes to osteogenic differentiation of hPDLSCs through the H19/Wnt/β-catenin axis

BackgroundStatic magnetic field (SMF) as an effective physical stimulus is capable of osteogenic differentiation for multiple mesenchymal stem cells, including human periodontal ligament stem cells (hPDLSCs). However, the exact molecular mechanism is still unknown. Therefore, this study intends to excavate molecular mechanisms related to SMF in hPDLSCs using functional experiments. MethodshPDLSCs were treated with different intensities of SMF, H19 lentivirus, and Wnt/β-catenin pathway inhibitor (XAV939). Changes in osteogenic markers (Runx2, Col Ⅰ, and BMP2), Wnt/β-catenin markers (β-catenin and GSK-3β), and calcified nodules were examined using RT-qPCR, western blotting, and alizarin red staining in hPDLSCs. ResultsSMF upregulated the expression of H19, and SMF and overexpressing H19 facilitated the expression of osteogenic markers (Runx2, Col Ⅰ, and BMP2), activation of the Wnt/β-catenin pathway, and mineralized sediment in hPDLSCs. Knockdown of H19 alleviated SMF function, and treatment with XAV939 limited SMF- and H19-mediated osteogenic differentiation of hPDLSCs. Notably, the expression of hsa-miR-532-3p, hsa-miR-370-3p, hsa-miR-18a-5p, and hsa-miR-483-3p in hPDLSCs was regulated by SMF, and may form an endogenous competitive RNA mechanism with H19 and β-catenin. ConclusionSMF contributes to the osteogenic differentiation of hPDLSCs by mediating the H19/Wnt/β-catenin pathway, and hsa-miR-532-3p, hsa-miR-370-3p, hsa-miR-18a-5p, and hsa-miR-483-3p may be the key factors in it.

Government size and the effectiveness of fiscal policy: the bigger the better?

Abstract This study investigates the effect of government size, as measured by the tax revenue to gross domestic product (tax-GDP) ratio, on output responses to increases in government purchases. First, we show that in a standard static neoclassical model, the stimulus effect of fiscal expansion on output increases with the tax-GDP ratio. This finding is quantitatively confirmed using a dynamic neoclassical model with standard functional forms and parameter values. To empirically test the theoretical findings, we analyze the responses of macroeconomic variables to an unanticipated increase in government purchases for 12 Organisation for Economic Cooperation and Development (OECD) countries during 1985–2019 using a state-dependent local projection method. The estimation results reveal that while output responses to an unanticipated fiscal expansion are significantly positive when the tax-GDP ratio is high, they are statistically indistinguishable from zero when the ratio is low. Overall, our findings suggest that fiscal expansion can stimulate output more effectively at high tax rates, unlike the well-known predictions of the traditional Keynesian model.