Intensity-dependent Changes Research Articles

Lipidome profiling of neutrophil-derived extracellular vesicles unveils their contribution to the ensemble of synovial fluid-derived extracellular vesicles during joint inflammation

The molecular signature of cell-derived extracellular vesicles (EVs) from synovial fluid (SF) offers insights into the cells and molecular processes associated with joint disorders and can be exploited to define biomarkers. The EV-signature is determined by cargo molecules and the lesser-studied lipid bilayer. We here investigated the lipidome of SF-EVs in inflamed joints derived from Rheumatoid Arthritis (RA) and Spondyloarthritis (SpA) patients, two autoimmune-driven joint diseases, and compared these signatures to the lipid profile of equine SF-EVs obtained during induced acute synovitis. Since neutrophils are primary SF-infiltrating cells during these inflammatory joint diseases, we also analyzed how inflammatory stimuli alter the lipidomic profile of human and equine neutrophil-derived EVs (nEVs) in vitro and how these signatures relate to the lipidome signatures of SF-EVs from inflamed joints. We identified neutrophil stimulation intensity-dependent changes in the lipidomic profile of nEVs with elevated presence of dihexosylceramide (lactosylceramide), phosphatidylserine, and phosphatidylethanolamine ether-linked lipid classes in human nEVs upon full neutrophil activation. In horses, levels of monohexosylceramide (glucosylceramide) increased instead of dihexosylceramide, indicating species-specific differences. The lipid profiles of RA and SpA SF-EVs were relatively similar and showed a relative resemblance with stimulated human nEVs. Similarly, the lipidome of equine synovitis-derived SF-EVs closer resembled the one of stimulated equine nEVs. Hence, lipidome profiling can provide insights into the contribution of nEVs to the heterogeneous pool of SF-EVs, deepening our understanding of inflammatory joint diseases and revealing molecular changes in joint homeostasis, which can lead to the development of more precise disease diagnosis and treatment strategies.

Beta tACS of varying intensities differentially affect resting-state and movement-related M1-M1 connectivity.

Due to the interconnected nature of the brain, changes in one region are likely to affect other structurally and functionally connected regions. Emerging evidence indicates that single-site transcranial alternating current stimulation (tACS) can modulate functional connectivity between stimulated and interconnected unstimulated brain regions. However, our understanding of the network response to tACS is incomplete. Here, we investigated the effect of beta tACS of different intensities on phase-based connectivity between the left and right primary motor cortices in 21 healthy young adults (13 female; mean age 24.30 ± 4.84 years). Participants underwent four sessions of 20 min of 20 Hz tACS of varying intensities (sham, 0.5 mA, 1.0 mA, or 1.5 mA) applied to the left primary motor cortex at rest. We recorded resting-state and event-related electroencephalography (EEG) before and after tACS, analyzing changes in sensorimotor beta (13-30 Hz) imaginary coherence (ImCoh), an index of functional connectivity. Event-related EEG captured movement-related beta activity as participants performed self-paced button presses using their right index finger. For resting-state connectivity, we observed intensity-dependent changes in beta ImCoh: sham and 0.5 mA stimulation resulted in an increase in beta ImCoh, while 1.0 mA and 1.5 mA stimulation decreased beta ImCoh. For event-related connectivity, 1.5 mA stimulation decreased broadband ImCoh (4-90 Hz) during movement execution. None of the other stimulation intensities significantly modulated event-related ImCoh during movement preparation, execution, or termination. Interestingly, changes in ImCoh during movement preparation following 1.0 mA and 1.5 mA stimulation were significantly associated with participants' pre-tACS peak beta frequency, suggesting that the alignment of stimulation frequency and peak beta frequency affected the extent of neuromodulation. Collectively, these results suggest that beta tACS applied to a single site influences connectivity within the motor network in a manner that depends on the intensity and frequency of stimulation. These findings have significant implications for both research and clinical applications.

Effects of the cardiac cycle on auditory processing: A preregistered study on mismatch negativity.

The systolic and diastolic phases of the cardiac cycle are known to affect perception and cognition differently. Higher order processing tends to be facilitated at systole, whereas sensory processing of external stimuli tends to be impaired at systole compared to diastole. The current study aims to examine whether the cardiac cycle affects auditory deviance detection, as reflected in the mismatch negativity (MMN) of the event-related brain potential (ERP). We recorded the intensity deviance response to deviant tones (70 dB) presented among standard tones (60 or 80 dB, depending on blocks) and calculated the MMN by subtracting standard ERP waveforms from deviant ERP waveforms. We also assessed intensity-dependent N1 and P2 amplitude changes by subtracting ERPs elicited by soft standard tones (60 dB) from ERPs elicited by loud standard tones (80 dB). These subtraction methods were used to eliminate phase-locked cardiac-related electric artifacts that overlap auditory ERPs. The endogenous MMN was expected to be larger at systole, reflecting the facilitation of memory-based auditory deviance detection, whereas the exogenous N1 and P2 would be smaller at systole, reflecting impaired exteroceptive sensory processing. However, after the elimination of cardiac-related artifacts, there were no significant differences between systole and diastole in any ERP components. The intensity-dependent N1 and P2 amplitude changes were not obvious in either cardiac phase, probably because of the short interstimulus intervals. The lack of a cardiac phase effect on MMN amplitude suggests that preattentive auditory processing may not be affected by bodily signals from the heart.

Neurovascular coupling during auditory stimulation: event-related potentials and fNIRS hemodynamic

Intensity-dependent amplitude changes (IDAP) have been extensively studied using event-related potentials (ERPs) and have been linked to several psychiatric disorders. This study aims to explore the application of functional near-infrared spectroscopy (fNIRS) in IDAP paradigms, which related to ERPs could indicate the existence of neurovascular coupling. Thirty-three and thirty-one subjects participated in two experiments, respectively. The first experiment consisted of the presentation of three-tone intensities (77.9 dB, 84.5 dB, and 89.5 dB) lasting 500 ms, each type randomly presented 54 times, while the second experiment consisted of the presentation of five-tone intensities (70.9 dB, 77.9 dB, 84.5 dB, 89.5 dB, and 94.5 dB) in trains of 8 tones lasting 70 ms each tone, the trains were presented 20 times. EEG was used to measure ERP components: N1, P2, and N1–P2 peak-to-peak amplitude. fNIRS allowed the analysis of the hemodynamic activity in the auditory, visual, and prefrontal cortices. The results showed an increase in N1, P2, and N1–P2 peak-to-peak amplitude with auditory intensity. Similarly, oxyhemoglobin and deoxyhemoglobin concentrations showed amplitude increases and decreases, respectively, with auditory intensity in the auditory and prefrontal cortices. Spearman correlation analysis showed a relationship between the left auditory cortex with N1 amplitude, and the right dorsolateral cortex with P2 amplitude, specifically for deoxyhemoglobin concentrations. These findings suggest that there is a brain response to auditory intensity changes that can be obtained by EEG and fNIRS, supporting the neurovascular coupling process. Overall, this study enhances our understanding of fNIRS application in auditory paradigms and highlights its potential as a complementary technique to ERPs.

Singlet Oxygen In Vivo: It Is All about Intensity-Part 2.

Recently, we reported induced anoxia as a limiting factor for photodynamic tumor therapy (PDT). This effect occurs in vivo if the amount of generated singlet oxygen that undergoes chemical reactions with cellular components exceeds the local oxygen supply. The amount of generated singlet oxygen depends mainly on photosensitizer (PS) accumulation, efficiency, and illumination intensity. With illumination intensities above a certain threshold, singlet oxygen is limited to the blood vessel and the nearest vicinity; lower intensities allow singlet oxygen generation also in tissue which is a few cell layers away from the vessels. While all experiments so far were limited to light intensities above this threshold, we report experimental results for intensities at both sides of the threshold for the first time, giving proof for the described model. Using time-resolved optical detection in NIR, we demonstrate characteristic, illumination intensity-dependent changes in signal kinetics of singlet oxygen and photosensitizer phosphorescence in vivo. The described analysis allows for better optimization and coordination of PDT drugs and treatment, as well as new diagnostic methods based on gated PS phosphorescence, for which we report a first in vivo feasibility test.

Optically tunable bianisotropy in a sphere made from an epsilon-near-zero material.

Bianisotropic media can be used to engineer absorbance, scattering, polarization, and dispersion of electromagnetic waves. However, the demonstration of a tunable light-induced bianisotropy at optical frequencies is still lacking. Here, we propose an experimentally feasible concept for a light-induced tunable bianisotropic response in a homogeneous sphere made of an epsilon-near-zero (ENZ) material. By exploiting the large linear absorption and the large possible intensity-dependent changes in the permittivity of ENZ materials, the direction-dependent scattering and absorption cross sections could be obtained. Our findings pave the way for further studies and applications in the optical regime requiring full dynamic control of the bianisotropic behavior.

Intensity-Dependent Changes in Quantified Resting Cerebral Perfusion With Multiple Sessions of Transcranial DC Stimulation.

Transcranial direct current stimulation (tDCS) to the left prefrontal cortex has been shown to produce broad behavioral effects including enhanced learning and vigilance. Still, the neural mechanisms underlying such effects are not fully understood. Furthermore, the neural underpinnings of repeated stimulation remain understudied. In this work, we evaluated the effects of the repetition and intensity of tDCS on cerebral perfusion [cerebral blood flow (CBF)]. A cohort of 47 subjects was randomly assigned to one of the three groups. tDCS of 1- or 2-mA was applied to the left prefrontal cortex on three consecutive days, and resting CBF was quantified before and after stimulation using the arterial spin labeling MRI and then compared with a group that received sham stimulation. A widespread decreased CBF was found in a group receiving sham stimulation across the three post-stimulation measures when compared with baseline. In contrast, only slight decreases were observed in the group receiving 2-mA stimulation in the second and third post-stimulation measurements, but more prominent increased CBF was observed across several brain regions including the locus coeruleus (LC). The LC is an integral region in the production of norepinephrine and the noradrenergic system, and an increased norepinephrine/noradrenergic activity could explain the various behavioral findings from the anodal prefrontal tDCS. A decreased CBF was observed in the 1-mA group across the first two post-stimulation measurements, similar to the sham group. This decreased CBF was apparent in only a few small clusters in the third post-stimulation scan but was accompanied by an increased CBF, indicating that the neural effects of stimulation may persist for at least 24 h and that the repeated stimulation may produce cumulative effects.

P 60. Influence of TMS intensity on the ipsilateral silent period - comparison of RMT-adjusted and maximum stimulator output intensities

Introduction. Transcranial magnetic stimulation (TMS) induced ipsilateral silent periods (iSP) provide information on interhemispheric inhibitory drive, but varying methodological approaches in equipment, measurement, and data analysis hamper the comparability and overall reproducibility. Even though it is generally agreed that only pulses above resting motor threshold (RMT) result in reliable occurrence of iSPs, studies differ on intensity conditions, either using fixed % maximum stimulator outputs (MSO) or individualized intensities based on RMT 1,2 . Our aim was to demonstrate the intensity-dependent changes of iSP parameters and to analyse which intensity configuration, either plotted by RMT or MSO values, predict the effect with a better fit. Method. We investigated 20 (9 F) right-handed healthy adults between 24y and 67y (M = 38.55, SD = 12.11) using navigated TMS. 50% maximal voluntary contraction of the left first dorsal interosseous muscle was performed during stimulation with intensities of 120%, 150%, 175%, and 200% RMT on the dominant motor hand area. A regression analysis was performed with RMT-adjusted states and their respective percentage of MSO as independent variable each for iSP onset, duration, and depth. Results. Overall, we found 54 iSPs across all states. In 12 cases, highest RMT states could not be reached due to stimulator output limits, in 14 recordings iSPs were missing. Neither MSO nor RMT intensity correlated with iSP onset. Duration increase was significantly associated with RMT intensity ( p = .013, r = .33), but not with MSO values ( p = .17, r = .16). Contrary, depth increase was significantly associated with MSO intensity ( p = .049, r = .26), with a trend for the RMT model ( p = .096, r = .22). Discussion. We here demonstrate an intensity-dependent increase in iSP duration and depth, but not onset. Additionally, we did not find a clear difference between the RMT or the MSO approach for the correlation of stimulus intensity to iSP depth or duration. Contrary to previous findings 1,3 , no evidence of a ceiling effect emerged from our data. Our data suggest that each aspect of the iSP has a different association with increasing TMS intensities. Considering the lacking power for analysis of iSP depth and diverging results further investigation with larger samples is needed to compare the effects of fixed MSO versus RMT-adjusted stimulation increase on iSP measurements. 1: Chen et al., 2003. J. Neurophysiol. 89, 1256–1264. 2: Davidson, T., 2016. In: Tremblay, F. (Ed.), Doctor of Philosophy in Human Kinetics. University of Ottawa. 3: Meyer et al. 1995. Brain 118, 429–440.

Age and Sport Intensity-Dependent Changes in Cytokines and Telomere Length in Elite Athletes.

Exercise-associated immune response plays a crucial role in the aging process. The aim of this study is to investigate the effect of sport intensity on cytokine levels, oxidative stress markers and telomere length in aging elite athletes. In this study, 80 blood samples from consenting elite athletes were collected for anti-doping analysis at an anti-doping laboratory in Italy (FMSI). Participants were divided into three groups according to their sport intensity: low-intensity skills and power sports (LI, n = 18); moderate-intensity mixed soccer players (MI, n = 31); and high-intensity endurance sports (HI, n = 31). Participants were also divided into two age groups: less than 25 (n = 45) and above 25 years old (n = 35). Serum levels of 10 pro and anti-inflammatory cytokines and two antioxidant enzymes were compared in age and sport intensity groups and telomere lengths were measured in their respective blood samples. Tumor necrosis factor-alpha (TNF-α) was the only cytokine showing significantly higher concentration in older athletes, regardless of sport intensity. Interleukin (IL)-10 increased significantly in HI regardless of age group, whereas IL-6 concentration was higher in the older HI athletes. IL-8 showed a significant interaction with sport intensity in different age groups. Overall, significant positive correlations among levels of IL-6, IL-10, IL-8 and TNF-α were identified. The antioxidant catalase activity was positively correlated with levels of TNF-α. Telomere length increased significantly with sport intensity, especially in the younger group. HI had longer telomeres and higher levels of pro- and anti-inflammatory cytokines, suggesting less aging in HI compared to low and moderate counterparts in association with heightened immune response. Investigation of the functional significance of these associations on the health and performance of elite athletes is warranted.

Mild blast wave exposure produces intensity-dependent changes in MMP2 expression patches in rat brains – Findings from different blast severities

Matrix metalloproteinase 2 (MMP2) is a gelatinase with multiple functions at the neurovascular interface, including local modification of the glia limitans to facilitate access of immune cells into the brain and amyloid-beta degradation during responses to injury or disease. This study examines regional changes in immunoreactive MMP2 in the rat brain after a single mild (2.7–7.9 psi peak) or moderate (13–17.5 psi peak) blast overpressure (BOP) exposure. Immunopositive MMP2 expression was examined quantitatively in histological sections of decalcified rat heads as a marker at 2, 24, and 72 h after BOP. The MMP2 immunoreactivity was isolated to patchy deposits in brain parenchyma surrounding blood vessels. Separate analyses were conducted for the cerebellum, brain stem caudal to the thalamo-mesencephalic junction, and the cerebrum (including diencephalon). The deposits varied in number, size, staining homogeneity (standard deviation of immunopositive region), and a cumulative measure, the product of size, average intensity and number, as a function of blast intensity and time. The sequences of changes in MMP2 spots from sham control animals suggested that the mild BOP exposure differences normalized within 72 h. However, the responses to moderate exposure revealed a delayed response at 72 h in the subtentorial brain stem and the cerebrum, but not the cerebellum. Hence, local MMP2 responses may be a contextual biomarker for locally regulated responses to widely distributed brain injury foci.

Nitric oxide coordinates growth, development, and stress response via histone modification and gene expression.

Nitric oxide (NO) is a signaling molecule with multiple regulatory functions in plant physiology and stress response. In addition to direct effects on transcriptional machinery, NO executes its signaling function via epigenetic mechanisms. We report that light intensity-dependent changes in NO correspond to changes in global histone acetylation (H3, H3K9, and H3K9/K14) in Arabidopsis (Arabidopsis thaliana) wild-type leaves, and that this relationship depends on S-nitrosoglutathione reductase and histone deacetylase 6 (HDA6). The activity of HDA6 was sensitive to NO, demonstrating that NO participates in regulation of histone acetylation. Chromatin immunoprecipitation sequencing and RNA-seq analyses revealed that NO participates in the metabolic switch from growth and development to stress response. This coordinating function of NO might be particularly important in plant ability to adapt to a changing environment, and is therefore a promising foundation for mitigating the negative effects of climate change on plant productivity.

Exercise training intensity-dependent adaptive changes in the cardiorespiratory function

Exercise training intensity-dependent adaptive changes in the cardiorespiratory function

Exercise training intensity-dependent adaptive changes in the cardiorespiratory function

Exercise training intensity-dependent adaptive changes in the cardiorespiratory function

Changes in circulating microRNA and arterial stiffness following high-intensity interval and moderate intensity continuous exercise.

High‐intensity interval (HII) exercise elicits distinct vascular responses compared to a matched dose of moderate intensity continuous (MOD) exercise. However, the acute effects of HII compared to MOD exercise on arterial stiffness are incompletely understood. Circulating microRNAs (ci‐miRs) may contribute to the vascular effects of exercise. We sought to determine exercise intensity‐dependent changes in ci‐miR potentially underlying changes in arterial stiffness. Ten young, healthy men underwent well‐matched, 30‐min HII and MOD exercise bouts. RT‐qPCR was used to determine the levels of seven vascular‐related ci‐miRs in serum obtained immediately before and after exercise. Arterial stiffness measures including carotid to femoral pulse wave velocity (cf‐PWV), carotid arterial compliance and β‐stiffness, and augmentation index (AIx and AIx75) were taken before, 10min after and 60min after exercise. Ci‐miR‐21‐5p, 126‐3p, 126‐5p, 150‐5p, 155‐5p, and 181b‐5p increased after HII exercise (p < .05), while ci‐miR‐150‐5p and 221‐3p increased after MOD exercise (p = .03 and 0.056). One hour after HII exercise, cf‐PWV trended toward being lower compared to baseline (p = .056) and was significantly lower compared to 60min after MOD exercise (p = .04). Carotid arterial compliance was increased 60min after HII exercise (p = .049) and was greater than 60min after MOD exercise (p = .02). AIx75 increased 10 min after both HII and MOD exercise (p < .05). There were significant correlations between some of the exercise‐induced changes in individual ci‐miRs and changes in cf‐PWV and AIx/AIx75. These results support the hypotheses that arterial stiffness and ci‐miRs are altered in an exercise intensity‐dependent manner, and ci‐miRs may contribute to changes in arterial stiffness.

Electrophysiological monitoring of pain afferent pathway of the trigeminal nerve and its functional plasticity in response to occlusal interference in rats

To observe the effect of occlusal interference on the afferent pathway of the trigeminal nerve and neuronal excitability in the trigeminal subnucleus caudalis (SPVC) of rats by electrical stimulation of the trigeminal ganglion (TG) and extracellular recordings of SPVC activities. Twenty male Wistar rats were randomly divided into control group and model group (n=10). In the model group, occlusal interference for 30 consecutive days was induced using light-cured flowable resin on the right maxillary molars. During occlusal interference, the pain sensitivity was scored with von Frey Fibers in the masseter. Simultaneous recordings of electrical activities from the SPVC, electrocardiogram, body temperature and electromyogram of the breath muscles of the anesthetized rats were performed, and the responses evoked by electrical stimulation of the TG were analyzed. Compared with the control rats, the rats in the model group showed significantly increased pain sensitivity scores (P < 0.05) and increased spontaneous discharge frequency of the SPVC (P < 0.05). The amplitude of the SPVC responses induced by electrical stimulation of the TG showed stimulus intensity-dependent changes (P < 0.05), and the amplitude evoked by 4 mA and 8 mA stimulation was similar between the model group and the control group (P>0.05). Train stimulation (0.2 ms, 1 mA, 30 s, 100 Hz) of the TG significantly increased the discharge frequency of the SPVC only in the rats in the model group (P < 0.05). The functional activities of the pain afferent pathway of the trigeminal nerve can be electrophysiologically monitored by electrical stimulation of the TG and extracellular recordings of SPVC activities in rats. Occlusal interference can increase the excitability of the neurons in the SPVC and enhance their sensitivities to TG afferent activation, suggesting the neural plasticity of the pain afferent pathway.

Uncovering the molecular signature underlying the light intensity-dependent root development in Arabidopsis thaliana

BackgroundRoot morphology is known to be affected by light quality, quantity and direction. Light signal is perceived at the shoot, translocated to roots through vasculature and further modulates the root development. Photoreceptors are differentially expressed in both shoot and root cells. The light irradiation to the root affects shoot morphology as well as whole plant development. The current work aims to understand the white light intensity dependent changes in root patterning and correlate that with the global gene expression profile.ResultsDifferent fluence of white light (WL) regulate overall root development via modulating the expression of a specific set of genes. Phytochrome A deficient Arabidopsis thaliana (phyA-211) showed shorter primary root compared to phytochrome B deficient (phyB-9) and wild type (WT) seedlings at a lower light intensity. However, at higher intensity, both mutants showed shorter primary root in comparison to WT. The lateral root number was observed to be lowest in phyA-211 at intensities of 38 and 75 μmol m − 2 s − 1. The number of adventitious roots was significantly lower in phyA-211 as compared to WT and phyB-9 under all light intensities tested. With the root phenotypic data, microarray was performed for four different intensities of WL light in WT. Here, we identified ~ 5243 differentially expressed genes (DEGs) under all light intensities. Gene ontology-based analysis indicated that different intensities of WL predominantly affect a subset of genes having catalytic activity and localized to the cytoplasm and membrane. Furthermore, when root is irradiated with different intensities of WL, several key genes involved in hormone, light signaling and clock-regulated pathways are differentially expressed.ConclusionUsing genome wide microarray-based approach, we have identified candidate genes in Arabidopsis root that responded to the changes in light intensities. Alteration in expression of genes such as PIF4, COL9, EPR1, CIP1, ARF18, ARR6, SAUR9, TOC1 etc. which are involved in light, hormone and clock pathway was validated by qRT-PCR. This indicates their potential role in light intensity mediated root development.

Nonlinear thermal and electronic optical properties of graphene in N-methylpyrrolidone at 800 nm with femtosecond laser pulses

Graphene is a useful saturable absorber in a variety of lasers working in mode-locking or Q-switch regimes. The optical performance of chemically synthesized graphene is still not completely characterized. In this study, the saturable absorption and the nonlinear refractive index of graphene flakes in N-methylpyrrolidone, in both liquid and solid phases, have been studied at 800 nm with the z-scan technique using femtosecond laser pulses. The results obtained using a Ti:sapphire laser oscillator in the mode-locking regime (6 fs, 78 MHz) or in the continuous wave shows that the optical properties of graphene have a thermal origin, while at the lower repetition rate and higher energy and intensity of a Ti:sapphire amplifier (95 fs, 1 kHz), it shows the electronic Kerr effect. Solid samples with very high optical densities, equivalent to 60 layers of graphene grown by chemical vapor deposition (CVD), can be fabricated. They show a higher saturation intensity (Is≈100 GW cm–2) than CVD-grown (74 MW cm–2) or epitaxially grown (4 GW cm–2) graphene and intensity-dependent changes in transmission from 25% to 43%. This change in transmission in multilayer solid samples points to a good performance as a saturable absorber in laser cavities.

Electrical Nerve Stimulation Elicits Intensity-dependent Changes in Force Steadiness in Young and Older Adults

When individuals attempt to match a submaximal target force by performing a steady isometric contraction, the fluctuations in force are often quantified as force steadiness (coefficient of variation [CV] for force) to provide an index of the neural drive to muscle. PURPOSE: To compare force steadiness of the wrist extensors during evoked and voluntary submaximal contractions in young and older adults. METHODS: Thirteen young (5 men, 25 ± 4 yrs) and 12 older (7 men, 78 ± 5 yrs) adults participated in a 1-hr protocol that involved maximal voluntary contractions (MVCs) and voluntary and evoked isometric contractions to match a 10% MVC target force. Force steadiness during the voluntary contraction was compared with that evoked by wide, high-frequency (1 ms pulses at 100 Hz) and narrow, low-frequency (0.2 ms pulses at 50 Hz) neuromuscular electrical stimulation (NMES), and a voluntary contraction with superimposed submotor transcutaneous electrical stimulation (TENS). CV for force was compared between age groups with unpaired t-tests and within age groups by paired t-tests. RESULTS: CV for force was less for young adults (1.82 ± 0.43%) than older adults (2.80 ± 1.08%) during the voluntary contraction with the wrist extensors (p<0.03). Force steadiness did not differ between age groups during the evoked contractions. However, older adults were steadier during both types of NMES (wide: 2.01 ± 0.67%, p<0.04; narrow: 1.69 ± 0.62%, p<0.02) than during the voluntary contractions (2.80 ± 1.08%). Concurrent TENS did not influence force steadiness for older adults, but young adults were less steady during TENS (2.41 ± 1.02%, p<0.03) than during the voluntary contraction by itself (1.82 ± 0.43%). CONCLUSION: The improvement in force steadiness for older adults during the NMES-evoked contractions indicates that the age-associated decline in force steadiness is attributable to changes in the neural drive to muscle, rather than the mechanical properties of muscle. In contrast, the decline in force steadiness for young adults during concurrent TENS suggests that heightened sensory feedback compromised the neural drive to muscle during the steady contraction.

Regulation of cerebral blood flow and metabolism during exercise.

What is the topic of this review? The manuscript collectively combines the experimental observations from >100 publications focusing on the regulation of cerebral blood flow and metabolism during exercise from 1945 to the present day. What advances does it highlight? This article highlights the importance of traditional and historical assessments of cerebral blood flow and metabolism during exercise, as well as traditional and new insights into the complex factors involved in the integrative regulation of brain blood flow and metabolism during exercise. The overarching theme is the importance of quantifying cerebral blood flow and metabolism during exercise using techniques that consider multiple volumetric cerebral haemodynamics (i.e. velocity, diameter, shear and flow). Cerebral function in humans is crucially dependent upon continuous oxygen delivery, metabolic nutrients and active regulation of cerebral blood flow (CBF). As a consequence, cerebrovascular function is precisely titrated by multiple physiological mechanisms, characterized by complex integration, synergism and protective redundancy. At rest, adequate CBF is regulated through reflexive responses in the following order of regulatory importance: fluctuating arterial blood gases (in particularly, partial pressure of carbon dioxide), cerebral metabolism, arterial blood pressure, neurogenic activity and cardiac output. Unfortunately, the magnitude that these integrative and synergistic relationships contribute to governing the CBF during exercise remains unclear. Despite some evidence indicating that CBF regulation during exercise is dependent on the changes of blood pressure, neurogenic activity and cardiac output, their role as a primary governor of the CBF response to exercise remains controversial. In contrast, the balance between the partial pressure of carbon dioxide and cerebral metabolism continues to gain empirical support as the primary contributor to the intensity-dependent changes in CBF observed during submaximal, moderate and maximal exercise. The goal of this review is to summarize the fundamental physiology and mechanisms involved in regulation of CBF and metabolism during exercise. The clinical implications of a better understanding of CBF during exercise and new research directions are also outlined.

High-Intensity Locomotor Exercise Increases Brain-Derived Neurotrophic Factor in Individuals with Incomplete Spinal Cord Injury.

High-intensity locomotor exercise is suggested to contribute to improved recovery of locomotor function after neurological injury. This may be secondary to exercise-intensity-dependent increases in neurotrophin expression demonstrated previously in control subjects. However, rigorous examination of intensity-dependent changes in neurotrophin levels is lacking in individuals with motor incomplete spinal cord injury (SCI). Therefore, the primary aim of this study was to evaluate the effect of locomotor exercise intensity on peripheral levels of brain-derived neurotrophic factor (BDNF) in individuals with incomplete SCI. We also explored the impact of the Val66Met single-nucleotide polymorphism (SNP) on the BDNF gene on intensity-dependent changes. Serum concentrations of BDNF and insulin-like growth factor-1 (IGF-1), as well as measures of cardiorespiratory dynamics, were evaluated across different levels of exercise intensity achieved during a graded-intensity, locomotor exercise paradigm in 11 individuals with incomplete SCI. Our results demonstrate a significant increase in serum BDNF at high, as compared to moderate, exercise intensities (p = 0.01) and 15 and 30 min post-exercise (p < 0.01 for both), with comparison to changes at low intensity approaching significance (p = 0.05). Serum IGF-1 demonstrated no intensity-dependent changes. Significant correlations were observed between changes in BDNF and specific indicators of exercise intensity (e.g., rating of perceived exertion; R = 0.43; p = 0.02). Additionally, the data suggest that Val66Met SNP carriers may not exhibit intensity-dependent changes in serum BDNF concentration. Given the known role of BDNF in experience-dependent neuroplasticity, these preliminary results suggest that exercise intensity modulates serum BDNF concentrations and may be an important parameter of physical rehabilitation interventions after neurological injury.