A Comparison of Muscle Sympathetic Nerve Activity to Non-contracting Muscle During Isometric Exercise in the Upper and Lower Limbs

Previous research indicates that greater sympathetic vasoconstrictor drive to skeletal muscle occurs during isometric upper limb exercise compared to lower limb exercise. However, potential disparity between blood flow and metaboreflex activation in contracting upper and lower limbs could contribute to the augmented sympathetic response during upper limb exercise. Therefore, the aim of this study was to examine MSNA responses during ankle dorsiflexion and handgrip exercise under ischaemic conditions, in order to standardize the conditions in terms of perfusion and metaboreflex activation. Eight healthy male subjects performed 4-min contractions of ischaemic isometric handgrip and ankle dorsiflexion at ∼10% maximal voluntary contraction, followed by 6 min of post-exercise ischaemia. MSNA was recorded continuously by microneurography of the common peroneal nerve of the non-contracting leg and quantified from negative-going sympathetic spikes in the neurogram, synchronized with the cardiac cycle. The time-course of MSNA exhibited parallel increases during exercise of the upper and lower limbs, rising throughout the contraction to peak at 4 min. This represented an increase of 100% relative to resting levels for handgrip exercise (66 ± 24 vs. 33 ± 7 spikes/min at rest) and 103% for dorsiflexion (63 ± 25 vs. 31 ± 8 spikes/min at rest; P < 0.01). In both conditions MSNA remained elevated during post-exercise ischaemia and returned to pre-contraction levels during recovery. These findings demonstrate that that the MSNA response to metaboreflex activation is similar for upper and lower limb exercise when perfusion is controlled for

The role of central command in the increase in muscle sympathetic nerve activity to contracting muscle during high intensity isometric exercise

We previously demonstrated that muscle sympathetic nerve activity (MSNA) increases to contracting muscle as well as to non-contracting muscle, but this was only assessed during isometric exercise at ∼10% of maximum voluntary contraction (MVC). Given that high-intensity isometric contractions will release more metabolites, we tested the hypothesis that the metaboreflex is expressed in the contracting muscle during highintensity but not low-intensity exercise. MSNA was recorded continuously via a tungsten microelectrode inserted percutaneously into the right common peroneal nerve in 12 participants, performing isometric dorsiflexion of the right ankle at 10, 20, 30, 40, and 50% MVC for 2 min. Contractions were immediately followed by 6 min of post-exercise schemia (PEI); 6 min of recovery separated contractions. Cross-correlation analysis was performed between the negative-going sympathetic spikes of the raw neurogram and the ECG. MSNA increased as contraction intensity increased, reaching mean values (± SD) of 207 ± 210 spikes/min at 10% MVC (P = 0.04), 270 ± 189 spikes/min at 20% MVC (P < 0.01), 538 ± 329 spikes/min at 30% MVC (P < 0.01), 816 ± 551 spikes/min at 40% MVC (P < 0.01), and 1,097 ± 782 spikes/min at 50% MVC (P < 0.01). Mean arterial pressure also increased in an intensity-dependent manner from 76 ± 3 mmHg at rest to 90 ± 6 mmHg (P < 0.01) during contractions of 50% MVC. At all contraction intensities, blood pressure remained elevated during PEI, but MSNA returned to pre-contraction levels, indicating that the metaboreflex does not contribute to the increase in MSNA to contracting muscle even at these high contraction intensitie

Robust and Fast Whole Brain Mapping of the RF Transmit Field B1 at 7T

In-vivo whole brain mapping of the radio frequency transmit field B1+ is a key aspect of recent method developments in ultra high field MRI. We present an optimized method for fast and robust in-vivo whole-brain B1+ mapping at 7T. The method is based on the acquisition of stimulated and spin echo 3D EPI images and was originally developed at 3T. We further optimized the method for use at 7T. Our optimization significantly improved the robustness of the method against large B1+ deviations and off-resonance effects present at 7T. The mean accuracy and precision of the optimized method across the brain was high with a bias less than 2.6 percent unit (p.u.) and random error less than 0.7 p.u. respectively

Using Motor Tempi to Understand Rhythm and Grammatical Skills in Developmental Language Disorder and Typical Language Development

Children with developmental language disorder (DLD) show relative weaknesses on rhythm tasks beyond their characteristic linguistic impairments. The current study compares preferred tempo and the width of an entrainment region for 5- to 7-year-old typically developing (TD) children and children with DLD and considers the associations with rhythm aptitude and expressive grammar skills in the two populations. Preferred tempo was measured with a spontaneous motor tempo task (tapping tempo at a comfortable speed), and the width (range) of an entrainment region was measured by the difference between the upper (slow) and lower (fast) limits of tapping a rhythm normalized by an individual’s spontaneous motor tempo. Data from N = 16 children with DLD and N = 114 TD children showed that whereas entrainment-region width did not differ across the two groups, slowest motor tempo, the determinant of the upper (slow) limit of the entrainment region, was at a faster tempo in children with DLD vs. TD. In other words, the DLD group could not pace their slow tapping as slowly as the TD group. Entrainment-region width was positively associated with rhythm aptitude and receptive grammar even after taking into account potential confounding factors, whereas expressive grammar did not show an association with any of the tapping measures. Preferred tempo was not associated with any study variables after including covariates in the analyses. These results motivate future neuroscientific studies of low-frequency neural oscillatory mechanisms as the potential neural correlates of entrainment-region width and their associations with musical rhythm and spoken language processing in children with typical and atypical language development

Clinical risk stratification of paediatric renal transplant recipients using C1q and C3d fixing of de novo donor-specific antibodies

Introduction: We have previously shown that children who developed de novo donor-specific human leukocyte antigen (HLA) antibodies (DSA) had greater decline in allograft function. We hypothesised that patients with complement-activating DSA would have poorer renal allograft outcomes. Methods: A total of 75 children developed DSA in the original study. The first positive DSA sample was subsequently tested for C1q and C3d fixing. The primary event was defined as 50% reduction from baseline estimated glomerular filtration rate and was analysed using the Kaplan–Meier estimator. Results: Of 65 patients tested, 32 (49%) and 23 (35%) tested positive for C1q and C3d fixing, respectively. Of the 32 C1q-positive (c1q+) patients, 13 (41%) did not show concomitant C3d fixing. The mean fluorescence intensity values of the original immunoglobulin G DSA correlated poorly with complement-fixing positivity (C1q: adjusted R2 0.072; C3d: adjusted R2 0.11; p < 0.05). C1q+ antibodies were associated with acute tubulitis [0.75 ± 0.18 (C1q+) vs. 0.25 ± 0.08 (C1q−) episodes per patient (mean ± standard error of the mean; p < 0.05] but not with worse long-term renal allograft dysfunction (median time to primary event 5.9 (C1q+) vs. 6.4 (C1q−) years; hazard ratio (HR) 0.74; 95% confidence ratio (CI) 0.30–1.81; p = 0.58]. C3d-positive (C3d+) antibodies were associated with positive C4d histological staining [47% (C3d+) vs. 20% (C3d−); p = 0.04] and with significantly worse long-term allograft dysfunction [median time to primary event: 5.6 (C3d+) vs. 6.5 (C3d−) years; HR 0.38; 95% CI 0.15–0.97; p = 0.04]. Conclusion: Assessment of C3d fixing as part of prospective HLA monitoring can potentially aid stratification of patients at the highest risk of long-term renal allograft dysfunction

The Stability and Repeatability of Spontaneous Sympathetic Baroreflex Sensitivity in Healthy Young Individuals

Spontaneous sympathetic baroreflex sensitivity (BRS) is a valuable tool for assessing how well the baroreflex buffers beat-to-beat changes in blood pressure. However, there has yet to be a study involving appropriate statistical tests to examine the stability of sympathetic BRS within an experimental session and the repeatability between separate sessions. The aim of this study was to use intra-class correlations, ordinary least products regression, and Bland–Altman analyses to examine the stability and repeatability of spontaneous sympathetic BRS assessment. In addition, the influence of recording duration on values of BRS was assessed. In eighty-four healthy young individuals (49 males, 35 females), continuous measurements of blood pressure, heart rate and muscle sympathetic nerve activity (MSNA) were recorded for 10 min. In a subgroup of 13 participants (11 male, 2 female) the measurements were repeated on a separate day. Sympathetic BRS was quantified using MSNA burst incidence (BRSinc) and total MSNA (BRStotal) for the first 5-min period, the second 5-min period, and a 2-min segment taken from the second 5-min period. Intra-class correlation coefficients indicated moderate stability in sympathetic BRSinc and BRStotal between the first and second 5-min periods in males (BRSincr = 0.63, BRStotalr = 0.78) and females (BRSincr = 0.61, BRStotalr = 0.47) with no proportional bias, but with fixed bias for BRSinc in females. When comparing the first 5-min with the 2-min period (n = 76), the intra-class correlation coefficient indicated poor to moderate repeatability in sympathetic BRSinc and BRStotal for males (BRSincr = -0.01, BRStotalr = 0.70) and females (BRSincr = 0.46, BRStotalr = 0.39). However, Bland–Altman analysis revealed a fixed bias for BRStotal in males and proportional bias for BRStotal in females, with lower BRS values for 5-min recordings. In the subgroup, intra-class correlations indicated moderate repeatability for measures of BRSinc (9 male, 2 female, r = 0.63) and BRStotal (6 male, 2 female, r = 0.68) assessed using 5-min periods recorded on separate days. However, Bland–Altman analysis indicated proportional bias for BRSinc and fixed bias for BRStotal. In conclusion, measures of spontaneous sympathetic BRS are moderately stable and repeatable within and between testing sessions in healthy young adults, provided that the same length of recording is used when making comparisons

Magnitude of the Morning Surge in Blood Pressure is Associated with Sympathetic but not Cardiac Baroreflex Sensitivity

The ability of the arterial baroreflex to regulate blood pressure may influence the magnitude of the morning surge in blood pressure. The aim was to investigate the relationships between sympathetic and cardiac baroreflex sensitivity (BRS) and the morning surge. Twenty-four hour ambulatory blood pressure was recorded in 14 young individuals. The morning surge was defined via the pre-awakening method, which is calculated as the difference between mean blood pressure values two hours before and two hours after rising from sleep. The mean systolic morning surge, diastolic morning surge and morning surge in mean arterial pressures were 15 ± 2 mmHg, 13 ± 1 mmHg and 11 ± 1 mmHg respectively. During the laboratory protocol, continuous measurements of blood pressure, heart rate and muscle sympathetic nerve activity (MSNA) were made over a 10-min period of rest. Sympathetic BRS was quantified by plotting MSNA burst incidence against diastolic pressure (sympathetic BRSinc), and by plotting total MSNA against diastolic pressure (sympathetic BRStotal). Cardiac BRS was quantified using the sequence method. The mean values for sympathetic BRSinc, sympathetic BRStotal and cardiac BRS were -1.26 ± 0.26 bursts/100hb/mmHg, -1.60 ± 0.37 AU/beat/mmHg and 13.1 ± 1.5 ms/mmHg respectively. Significant relationships were identified between sympathetic BRSinc and the diastolic morning surge (r =0.62, p =0.02) and the morning surge in mean arterial pressure (r =0.57, p =0.03). Low sympathetic BRS was associated with a larger morning surge in mean arterial and diastolic blood pressure. Trends for relationships were identified between sympathetic BRStotal and the diastolic morning surge (r =0.52, p =0.066) and the morning surge in mean arterial pressure (r =0.48, p =0.095) but these did not reach significance. There were no significant relationships between cardiac BRS and the morning surge. These findings indicate that the ability of the baroreflex to buffer increases in blood pressure via reflexive changes in MSNA may play a role in determining the magnitude of the morning surge in blood pressure

New evidence of a rhythmic priming effect that enhances grammaticality judgments in children

International audienc

New evidence of a rhythmic priming effect that enhances grammaticality judgments in children

International audienc

Contributions of central command and muscle feedback to sympathetic nerve activity in contracting human skeletal muscle

During voluntary contractions, muscle sympathetic nerve activity (MSNA) to contracting muscles increases in proportion to force but the underlying mechanisms are not clear. To shed light on these mechanisms, particularly the influences of central command and muscle afferent feedback, the present study tested the hypothesis that MSNA is greater during voluntary compared with electrically-evoked contractions. Seven male subjects performed a series of 1-minute isometric dorsiflexion contractions (left leg) separated by 2-minute rest periods, alternating between voluntary and electrically-evoked contractions at similar forces (5-10 % of maximum). MSNA was recorded continuously (microneurography) from the left peroneal nerve and quantified from cardiac-synchronised, negative-going spikes in the neurogram. Compared with pre-contraction values, MSNA increased by 51 ± 34 % (P < 0.01) during voluntary contractions but did not change significantly during electrically-evoked contractions (-8 ± 12 %, P > 0.05). MSNA analysed at 15-s intervals revealed that this effect of voluntary contraction appeared 15-30 s after contraction onset (P < 0.01), remained elevated until the end of contraction, and disappeared within 15 s after contraction. These findings suggest that central command, and not feedback from contracting muscle, is the primary mechanism responsible for the increase in MSNA to contracting muscle. The time-course of MSNA suggests that there is a longer delay in the onset of this effect compared with its cessation after contraction