Sham Control Condition Research Articles

Inhibition moderates the effect of attentional bias modification for reducing residual depressive symptoms: A randomized sham-controlled clinical trial

ObjectivesResidual symptoms represent risk factor for relapse. Attention bias modification (ABM) may reduce clinical and sub-clinical depressive symptoms, indicating that is may be of relevance when preventing relapse. Current evidence suggests that executive functions may moderate the outcome of interventions targeting depressive symptoms. MethodsWe assessed inhibition and shifting as indicators of executive functioning by means of the Color-Word Interference Test (i.e., “Stroop task”). These baseline characteristics were investigated as moderator of the effect of ABM on depression symptoms in a double-blinded randomized sham-controlled trial of ABM including patients with a history of recurrent depression (N = 301). Inclusion and follow-ups took place from January 2015 to October 2016. The trial was retrospectively registered #NCT02658682 January 2016. ResultsThe moderation analysis was based on the interaction term ABM x Stroop. Scaled inhibition scores ≤10.8, but not shifting ability, moderated the effect of ABM compared to sham on clinician-rated depression (HDRS). The difference from the 15th to the 85th percentile of the inhibition score was about 1 HDRS-point, indicating a small effect size. No moderation was found when self-reported depression and AB were the outcome. Post-hoc power calculation indicates risk of Type-II error. ConclusionWhen targeting depressive symptoms, ABM seems to be somewhat more effective in patients with weak inhibitory control. This suggests that evaluating the level of inhibition in individual patients could provide some information when making decisions about prescribing ABM to reduce residual symptoms, but the clinical implications of this is uncertain due to an overall small effect size attributable to ABM. Future studies should examine whether inhibitory control still is a relevant moderator when comparing ABM to treatment options other than the sham control condition.

Closed-loop transcutaneous auricular vagus nerve stimulation for the improvement of upper extremity motor function in stroke patients: a study protocol.

Transcutaneous auricular vagus nerve stimulation (taVNS) has garnered attention for stroke rehabilitation, with studies demonstrating its benefits when combined with motor rehabilitative training or delivered before motor training. The necessity of concurrently applying taVNS with motor training for post-stroke motor rehabilitation remains unclear. We aimed to investigate the necessity and advantages of applying the taVNS concurrently with motor training by an electromyography (EMG)-triggered closed-loop system for post-stroke rehabilitation. We propose a double-blinded, randomized clinical trial involving 150 stroke patients assigned to one of three groups: concurrent taVNS, sequential taVNS, or sham control condition. In the concurrent group, taVNS bursts will synchronize with upper extremity motor movements with EMG-triggered closed-loop system during the rehabilitative training, while in the sequential group, a taVNS session will precede the motor rehabilitative training. TaVNS intensity will be set below the pain threshold for both concurrent and sequential conditions and at zero for the control condition. The primary outcome measure is the Fugl-Meyer Assessment of Upper Extremity (FMA-UE). Secondary measures include standard upper limb function assessments, as well as EMG and electrocardiogram (ECG) features. Ethical approval has been granted by the Medical Ethics Committee, affiliated with Zhujiang Hospital of Southern Medical University for Clinical Studies (2023-QX-012-01). This study has been registered on ClinicalTrials (NCT05943431). Signed informed consent will be obtained from all included participants. The findings will be published in peer-reviewed journals and presented at relevant stakeholder conferences and meetings. This study represents a pioneering effort in directly comparing the impact of concurrent taVNS with motor training to that of sequential taVNS with motor training on stroke rehabilitation. Secondly, the incorporation of an EMG-triggered closed-loop taVNS system has enabled the automation and individualization of both taVNS and diverse motor training tasks-a novel approach not explored in previous research. This technological advancement holds promise for delivering more precise and tailored training interventions for stroke patients. However, it is essential to acknowledge a limitation of this study, as it does not delve into examining the neural mechanisms underlying taVNS in the context of post-stroke rehabilitation.

Increase in choroidal thickness after blue light stimulation of the blind spot in young adults.

Blue light activates melanopsin, a photopigment that is expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs). The axons of ipRGCs converge on the optic disc, which corresponds to the physiological blind spot in the visual field. Thus, a blue light stimulus aligned with the blind spot captures the ipRGCs axons at the optic disc. This study examined the potential changes in choroidal thickness and axial length associated with blue light stimulation of melanopsin-expressing ipRGCs at the blind spot. It was hypothesized that blue light stimulation at the blind spot in adults increases choroidal thickness. The blind spots of both eyes of 10 emmetropes and 10 myopes, with a mean age of 28 ± 6 years (SD), were stimulated locally for 1-minute with blue flickering light with a 460nm peak wavelength. Measurements of choroidal thickness and axial length were collected from the left eye before stimulation and over a 60-minute poststimulation period. At a similar time of day, choroidal thickness and axial length were measured under sham control condition in all participants, while a subset of 3 emmetropes and 3 myopes were measured after 1-minute of red flickering light stimulation of the blind spot with a peak wavelength of 620nm. Linear mixed model analyses were performed to examine the light-induced changes in choroidal thickness and axial length over time and between refractive groups. Compared with sham control (2 ± 1μm, n = 20) and red light (-1 ± 2μm, n = 6) stimulation, subfoveal choroidal thickness increased within 60min after blue light stimulation of the blind spot (7 ± 1μm, n = 20; main effect of light, p < 0.001). Significant choroidal thickening after blue light stimulation occurred in emmetropes (10 ± 2μm, p < 0.001) but not in myopes (4 ± 2μm, p > 0.05). Choroidal thickening after blue light stimulation was greater in the fovea, diminishing in the parafoveal and perifoveal regions. There was no significant main effect of light, or light by refractive error interaction on the axial length after blind spot stimulation. These findings demonstrate that stimulating melanopsin-expressing axons of ipRGCs at the blind spot with blue light increases choroidal thickness in young adults. This has potential implications for regulating eye growth.

The effects of prefrontal tDCS and hf-tRNS on the processing of positive and negative emotions evoked by video clips in first- and third-person

The causal role of the cerebral hemispheres in positive and negative emotion processing remains uncertain. The Right Hemisphere Hypothesis proposes right hemispheric superiority for all emotions, while the Valence Hypothesis suggests the left/right hemisphere's primary involvement in positive/negative emotions, respectively. To address this, emotional video clips were presented during dorsolateral prefrontal cortex (DLPFC) electrical stimulation, incorporating a comparison of tDCS and high frequency tRNS stimulation techniques and manipulating perspective-taking (first-person vs third-person Point of View, POV). Four stimulation conditions were applied while participants were asked to rate emotional video valence: anodal/cathodal tDCS to the left/right DLPFC, reverse configuration (anodal/cathodal on the right/left DLPFC), bilateral hf-tRNS, and sham (control condition). Results revealed significant interactions between stimulation setup, emotional valence, and POV, implicating the DLPFC in emotions and perspective-taking. The right hemisphere played a crucial role in both positive and negative valence, supporting the Right Hemisphere Hypothesis. However, the complex interactions between the brain hemispheres and valence also supported the Valence Hypothesis. Both stimulation techniques (tDCS and tRNS) significantly modulated results. These findings support both hypotheses regarding hemispheric involvement in emotions, underscore the utility of video stimuli, and emphasize the importance of perspective-taking in this field, which is often overlooked.

Frontal midline theta transcranial alternating current stimulation enhances early consolidation of episodic memory

Evidence implicating theta rhythms in declarative memory encoding and retrieval, together with the notion that both retrieval and consolidation involve memory reinstatement or replay, suggests that post-learning theta rhythm modulation can promote early consolidation of newly formed memories. Building on earlier work employing theta neurofeedback, we examined whether theta-frequency transcranial alternating stimulation (tACS) can engender effective consolidation of newly formed episodic memories, compared with beta frequency stimulation or sham control conditions. We compared midline frontal and posterior parietal theta stimulation montages and examined whether benefits to memory of theta upregulation are attributable to consolidation rather than to retrieval processes by using a washout period to eliminate tACS after-effects between stimulation and memory assessment. Four groups of participants viewed object pictures followed by a free recall test during three study-test cycles. They then engaged in tACS (frontal theta montage/parietal theta montage/frontal beta montage/sham) for a period of 20 min, followed by a 2-h break. Free recall assessments were conducted after the break, 24 h later, and 7 days later. Frontal midline theta-tACS induced significant off-line retrieval gains at all assessment time points relative to all other conditions. This indicates that theta upregulation provides optimal conditions for the consolidation of episodic memory, independent of mental-state strategies.

Slow waves during deep sleep support cardiac function

Introduction The role of sleep in cardiovascular health, particularly the impact of deep non-rapid eye movement (NREM) sleep, is gaining interest in the prevention of cardiovascular diseases (Grandner et al., 2016). Essentially slow waves, prominent brain oscillations during deep sleep, seem to represent an important cardiovascular recovery process for the human body. However, to date, the specific mechanisms through which sleep affects cardiovascular function and whether slow waves accelerate recovery remain elusive. Methods Here, we explored the role of slow waves in promoting cardiovascular function. In this randomized, cross-over trial involving 18 healthy male participants (Huwiler et al., 2023), we investigated how experimentally enhancing slow waves via auditory stimulation (Huwiler et al., 2022) impacts cardiovascular dynamics during sleep and next-day cardiac function, assessed via an echocardiography. All participants underwent three experimental nights including two conditions for slow wave enhancement and one SHAM control condition while brain oscillatory, blood pressure, and cardiac dynamics were continuously measured during sleep. Results Using a linear mixed-effect model approach, we found auditory stimulation to significantly increase slow wave activity (F(2, 33.095) = 11.397, p &lt; 0.001) during times of stimulation. This slow wave enhancement coincided with a dynamic cardiovascular activation, indicated through short increases in blood pressure and a biphasic heart rate response. After sleep, we found a significant increase in general longitudinal strain (F(2, 34) = 81.17, p &lt; 0.001), an increase in left-ventricular ejection fraction (F(2, 34) = 4.55, p = 0.018), and a decrease in E/e’ ratio (F(2, 34) = 3.38, p = 0.046) for both slow wave stimulation conditions compared to SHAM. Discussion/Conclusion We show that slow wave stimulation induces a cardiovascular activation response possibly related to increasing cardiovascular stability during sleep (De Zambotti et al., 2016). Moreover, we demonstrate that slow wave stimulation enhances left-ventricular systolic and diastolic function, both together indicating improved cardiac function. Altogether, this points towards the functional involvement of slow waves in promoting cardiovascular health. Therefore, sleep slow wave stimulation may be considered a potential supplementary method in treating cardiovascular diseases involving decreased left-ventricular function. Furthermore, our findings hint that enhancing slow waves could potentially optimize post-exercise recovery processes and increase cardiovascular well-being.

Utility of Repetitive Transcranial Magnetic Stimulation for Chronic Daily Headache Prophylaxis: A Systematic Review and Meta-Analysis.

Management of chronic daily headaches (CDH) remains challenging due to the limited efficacy of standard prophylactic pharmacological measures. Several studies have reported that repetitive transcranial magnetic stimulation (rTMS) can effectively treat chronic headaches. The objective was to determine the utility of rTMS for immediate post-treatment and sustained CDH prophylaxis. All procedures were conducted per PRISMA guidelines. PubMed, Scopus, Web of Science, and ProQuest databases were searched for controlled clinical trials that have tested the efficacy of rTMS on populations with CDH. DerSimonian-Laird random-effects meta-analyses were performed using the 'meta' package in R to examine the post- vs. pre-rTMS changes in standardized headache intensity and frequency compared to sham-control conditions. Thirteen trials were included with a combined study population of N = 538 patients with CDH (rTMS, N = 284; Sham, N = 254). Patients exposed to rTMS had significantly reduced standardized CDH intensity and frequency in the immediate post-treatment period (Hedges' g = -1.16 [-1.89, -0.43], p = 0.002 and Δ = -5.07 [-10.05, -0.11], p = 0.045 respectively). However, these effects were sustained marginally in the follow-up period (Hedges' g = -0.43 [-0.76, -0.09], p = 0.012 and Δ = -3.33 [-5.52, -1.14], p = 0.003). Significant between-study heterogeneity was observed, at least partially driven by variations in rTMS protocols. Despite the observed clinically meaningful and statistically significant benefits in the immediate post-treatment period, the prophylactic effects of rTMS on CDH do not seem to sustain with discontinuation. Thus, the cost-effectiveness of the routine use of rTMS for CDH prophylaxis remains questionable. Protocol preregistered in PROSPERO International Prospective Register of Systematic Reviews (CRD42021250100).

Abstract 1102: Establishing the cytotoxic benefit of Tumor Treating Fields on radiation sensitive and acquired radiation resistant glioblastoma patient derived xenograft pairs

Abstract Background: Glioblastoma (GBM) is the most common malignant primary brain tumor with very poor prognosis. The current standard of care for GBM consists of maximal safe tumor resection, chemotherapy (temozolomide) and radiotherapy followed by adjuvant temozolomide and Tumor Treating Fields (TTFields). Unfortunately, GBM displays both inherent and acquired resistance to temozolomide and radiation and is incurable. While TTFields have been found to broadly induce endoplasmic reticulum stress, autophagy, cell membrane permeability, DNA replication stress, anti-mitotic and anti-migratory effects, it is unclear how well TTFields impact radiation resistant GBM. To better understand the cytotoxic benefit of TTFields on acquired radiation resistant GBM, we tested patient-derived xenograft (PDX) brain tumor initiating cells (BTICs) that had been selected for radiation resistance and compared them to their radiation sensitive parent. Methods: PDX were developed with subcutaneous implantation of patient GBM cells into immunodeficient (nu/nu) mice. Acquired radiation resistant PDXs were generated through in vivo selection (6-8 passages) using six fractions of 2 Gray of radiation over two weeks. PDX BTICs were cultured on laminin-coated cover slips under serum free conditions. Cytotoxicity was measured on both the two-dimensional sham control and two-dimensional TTFields treatment conditions over the course of 72 hours and analyzed with crystal violet staining for both imaging and absorbance quantification. PamStation 12 Kinomic data and RNA-seq (Illumina) data was generated for each PDX. Results: Crystal violet quantification and representative imaging indicated that TTFields inhibit cell growth in both parental and acquired radiation resistant PDX-derived BTICs. There is an observed TTFields sensitivity response from the acquired radiation resistant PDX, indicating that TTFields treatment does have a cytotoxic effect on acquired radiation resistant models (seen over four reproducible experiments). Baseline kinomic and transcriptomic differences between the PDX lines suggest potential TTFields sensitivity signatures. Conclusions: Ongoing studies are focused on validation of this cytotoxic effect on larger cohort of both acquired and inherent radiation resistant PDX cells. We plan to measure TTFields -treatment induced kinomic alterations to identify downstream signaling pathways associated with TTFields treatment response, as well as the development of acquired TTFields resistant GBM PDX cells. Citation Format: Taylor L. Schanel, Amber B. Jones, Andee M. Beierle, Hasan Alrefai, Lauren C. Nassour, Patricia H. Hicks, Joshua C. Anderson, Anita B. Hjelmeland, Christopher D. Willey. Establishing the cytotoxic benefit of Tumor Treating Fields on radiation sensitive and acquired radiation resistant glioblastoma patient derived xenograft pairs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1102.

The Effects of Transcutaneous Vagus Nerve Stimulation on Functional Connectivity Within Semantic and Hippocampal Networks in Mild Cognitive Impairment.

Better treatments are needed to improve cognition and brain health in people with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Transcutaneous vagus nerve stimulation (tVNS) may impact brain networks relevant to AD through multiple mechanisms including, but not limited to, projection to the locus coeruleus, the brain's primary source of norepinephrine, and reduction in inflammation. Neuropathological data suggest that the locus coeruleus may be an early site of tau pathology in AD. Thus, tVNS may modify the activity of networks that are impaired and progressively deteriorate in patients with MCI and AD. Fifty patients with MCI (28 women) confirmed via diagnostic consensus conference prior to MRI (sources of info: Montreal Cognitive Assessment Test (MOCA), Clinical Dementia Rating scale (CDR), Functional Activities Questionnaire (FAQ), Hopkins Verbal Learning Test - Revised (HVLT-R) and medical record review) underwent resting state functional magnetic resonance imaging (fMRI) on a Siemens 3T scanner during tVNS (left tragus, n = 25) or sham control conditions (left ear lobe, n = 25). During unilateral left tVNS, compared with ear lobe stimulation, patients with MCI showed alterations in functional connectivity between regions of the brain that are important in semantic and salience functions including regions of the temporal and parietal lobes. Furthermore, connectivity from hippocampi to several cortical and subcortical clusters of ROIs also demonstrated change with tVNS compared with ear lobe stimulation. In conclusion, tVNS modified the activity of brain networks in which disruption correlates with deterioration in AD. These findings suggest afferent target engagement of tVNS, which carries implications for the development of noninvasive therapeutic intervention in the MCI population.

Ischaemic preconditioning blunts exercise-induced mitochondrial dysfunction, speeds oxygen uptake kinetics but does not alter severe-intensity exercise capacity.

What is the central question of this study? Ischaemic preconditioning is a novel pre-exercise priming strategy. We asked whether ischaemic preconditioning would alter mitochondrial respiratory function and pulmonary oxygen uptake kinetics and improve severe-intensity exercise performance. What is the main finding and its importance? Ischaemic preconditioning expedited overall pulmonary oxygen uptake kinetics and appeared to prevent an increase in leak respiration, proportional to maximal electron transfer system and ADP-stimulated respiration, that was evoked by severe-intensity exercise in sham-control conditions. However, severe-intensity exercise performance was not improved. The results do not support ischaemic preconditioning as a pre-exercise strategy to improve exercise performance in recreationally active participants. We examined the effect of ischaemic preconditioning (IPC) on severe-intensity exercise performance, pulmonary oxygen uptake ( ) kinetics, skeletal muscle oxygenation (muscle tissue O2 saturation index) and mitochondrial respiration. Eight men underwent contralateral IPC (4×5min at 220mmHg) or sham-control (SHAM; 20mmHg) before performing a cycling time-to-exhaustion test (92% maximum aerobic power). Muscle (vastus lateralis) biopsies were obtained before IPC or SHAM and ∼1.5min postexercise. The time to exhaustion did not differ between SHAM and IPC (249±37vs. 240±32s; P=0.62). Pre- and postexercise ADP-stimulated (P) and maximal (E) mitochondrial respiration through protein complexes (C) I, II and IV did not differ (P>0.05). Complex I leak respiration was greater postexercise compared with baseline in SHAM, but not in IPC, when normalized to wet mass (P=0.01vs. P=0.19), mitochondrial content (citrate synthase activity, P=0.003vs. P=0.16; CI+IIP, P=0.03vs. P=0.23) and expressed relative to P (P=0.006vs. P=0.30) and E (P=0.004vs. P=0.26). The mean response time was faster (51.3±15.5vs. 63.7±14.5s; P=0.003), with a smaller slow component (270±105vs. 377±188mlmin-1 ; P=0.03), in IPC compared with SHAM. The muscle tissue O2 saturation index did not differ between trials (P>0.05). Ischaemic preconditioning expedited kinetics and appeared to prevent an increase in leak respiration through CI, when expressed proportional to E and P evoked by severe-intensity exercise, but did not improve exercise performance.

Ischaemic preconditioning improves upper-body endurance performance without altering V̇O2 kinetics

ABSTRACT Purpose: Whilst pre-exercise ischaemic preconditioning (IPC) can improve lower-body exercise performance, its impact on upper-limb performance has received little attention. This study examines the influence of IPC on upper-body exercise performance and oxygen uptake (V̇O2) kinetics. Methods: Eleven recreationally-active males (24 ± 2 years) completed an arm-crank graded exercise test to exhaustion to determine the power outputs at the ventilatory thresholds (VT1 and VT2) and V̇O2peak (40.0 ± 7.4 ml·kg−1·min−1). Four main trials were conducted, two following IPC (4 × 5-min, 220 mmHg contralateral upper-limb occlusion), the other two following SHAM (4 × 5-min, 20 mmHg). The first two trials consisted of a 15-minute constant work rate and the last two time-to-exhaustion (TTE) arm-crank tests at the power equivalents of 95% VT1 (LOW) and VT2 (HIGH), respectively. Pulmonary V̇O2 kinetics, heart rate, blood-lactate concentration, and rating of perceived exertion were recorded throughout exercise. Results: TTE during HIGH was longer following IPC than SHAM (459 ± 115 vs 395 ± 102 s, p = .004). Mean response time and change in V̇O2 between 2-min and end exercise (ΔV̇O2) were not different between IPC and SHAM for arm-cranking at both LOW (80.3 ± 19.0 vs 90.3 ± 23.5 s [p = .06], 457 ± 184 vs 443 ± 245 ml [p = .83]) and HIGH (96.6 ± 31.2 vs 92.1 ± 24.4 s [p = .65], 617 ± 321 vs 649 ± 230 ml [p = .74]). Heart rate, blood-lactate concentration, and rating of perceived exertion did not differ between conditions (all p ≥ .05). Conclusion: TTE was longer following IPC during upper-body exercise despite unchanged V̇O2 kinetics. Highlights Whilst pre-exercise ischaemic preconditioning can improve lower-body exercise performance and alter V̇O2 kinetics, its impact on upper-limb performance has received little attention. An acute bout of ischaemic preconditioning prior to arm-crank ergometry exercise significantly improved time to exhaustion compared to a sham control condition. V̇O2 kinetics in response to ischaemic preconditioning remained unchanged, suggesting alternative mechanisms may explain performance improvements.

Effects of auditory sleep modulation approaches on brain oscillatory and cardiovascular dynamics.

Slow waves, the hallmark feature of deep nonrapid eye movement sleep, do potentially drive restorative effects of sleep on brain and body functions. Sleep modulation techniques to elucidate the functional role of slow waves thus have gained large interest. Auditory slow wave stimulation is a promising tool; however, directly comparing auditory stimulation approaches within a night and analyzing induced dynamic brain and cardiovascular effects are yet missing. Here, we tested various auditory stimulation approaches in a windowed, 10 s ON (stimulations) followed by 10 s OFF (no stimulations), within-night stimulation design and compared them to a SHAM control condition. We report the results of three studies and a total of 51 included nights and found a large and global increase in slow-wave activity (SWA) in the stimulation window compared to SHAM. Furthermore, slow-wave dynamics were most pronouncedly increased at the start of the stimulation and declined across the stimulation window. Beyond the changes in brain oscillations, we observed, for some conditions, a significant increase in the mean interval between two heartbeats within a stimulation window, indicating a slowing of the heart rate, and increased heart rate variability derived parasympathetic activity. Those cardiovascular changes were positively correlated with the change in SWA, and thus, our findings provide insight into the potential of auditory slow wave enhancement to modulate cardiovascular restorative conditions during sleep. However, future studies need to investigate whether the potentially increased restorative capacity through slow-wave enhancements translates into a more rested cardiovascular system on a subsequent day.

Obesity Exacerbates Lipid Nephrotoxicity and Renal Injury in a Model of Ovarian Hormone Deficiency

Obesity rates are continually increasing both in the USA and around the world. As rates of obesity continue to grow, public health concerns remain a top priority in order to curtail mortality and morbidity. An increase in visceral adipose tissue is correlated with dysfunction in multiple organs, including the kidneys. Increases in basal metabolic index, or BMI, has been linked to increases in triglyceride accumulation in the kidneys. Obesity accounts for ~25% of kidney diseases observed in women; however, its effects on kidney function have not been defined in post‐menopausal women. In an ovarian hormone deficient mouse model (ovariectomized animals), we measured a significant weight gain compared with sham‐operated control, associated with perirenal adipose tissue accumulation, and an increase in 1. glomerular filtration rate (GFR) used to determine renal function, 2. protein level of the NGAL, an early biomarker of kidney injury and 3. intrarenal lipid accumulation found in the renal tubules. In this study, we aim to determine whether obesity affects the levels of renal injury and lipid accumulation measured in a model of ovarian hormone deficiency. We studied four groups of mice: the first and second groups underwent ovariectomy (OVX); group one was fed a 60% high‐fat (HF) diet, and group two was on a 10% low‐fat (LH) diet. The third and fourth groups (controls), underwent surgery without ovariectomy (SHAM) and were fed a HF or LF diet. All animals had ad libitum access to their respective diet for fourteen weeks (i.e., ten weeks prior to surgery and four weeks after). Significant increase in body weight was measured in mice on HF compared to LF diet. The size of triglyceride droplets in the renal tubules was significantly higher (20‐25%) in OVX compared to SHAM‐operated control mice on both HF and LF diets. The Neutrophil Gelatinase Associated Lipocalin (NGAL) protein levels were measured as a biomarker of kidney injury. Levels of NGAL protein expression increased in OVX mice when compared to SHAM control in the renal tubules of mice on both HF (211.3 ± 3.7%, p&lt;0.0001) and LF diet (111.33 ± 1.7%, p=0.02). In the glomeruli, NGAL protein expression levels increased in OVX mice compared to SHAM control in HF (188.8 ± 9.9%, p&lt;0.0001) and LF diet fed groups (113.1 ± 4.9%, p=0.64). Furthermore, mice on HF diet had significant higher NGAL levels in OVX and sham‐control conditions than mice in the same conditions on LF diet. These findings indicate that weight gain exacerbates renal injury induced by OVX, and that estrogen may be protective against excessive accumulation of triglycerides in kidney structures. Our study supports the understanding of the mechanisms implicated in the development of kidney diseases in obese post‐menopausal women.

Effects of the Elevation Training Mask® 2.0 on dyspnea and respiratory muscle mechanics, electromyography, and fatigue during exhaustive cycling in healthy humans

ObjectivesExamine the effects of the Elevation Training Mask® 2.0 (ETM) on dyspnea, and respiratory muscle function and fatigue during exercise. DesignRandomized crossover. Methods10 healthy participants completed 2 time-to-exhaustion (TTE) cycling tests while wearing the ETM or under a sham control condition. During the sham, participants were told they were breathing air equivalent to “9000 ft” (matched to the selected resistance valves on the ETM according to the manufacturer), but they were breathing room air. Dyspnea and leg discomfort were assessed using the modified 0–10 category-ratio Borg scale. Qualitative dyspnea descriptors at peak exercise were selected from a list of 15. Crural diaphragmatic electromyography (EMGdi) and transdiaphragmatic pressure (Pdi) were measured via a multipair esophageal electrode balloon catheter. Participants performed maximal respiratory maneuvers before and after exercise to estimate the degree of respiratory muscle fatigue. ResultsExercise with the ETM resulted in a significant decrease in TTE (p = 0.015), as well as increased dyspnea at baseline (p = 0.032) and during the highest equivalent submaximal exercise time (p = 0.0001). The increase in dyspnea with the ETM was significantly correlated with the decrease in exercise time (r = 0.73, p = 0.020). EMGdi and Pdi were significantly increased with the ETM at all time points (all p < 0.05). There was a significant increase in the selection frequency of “my breath does not go in all the way” at peak exercise with the ETM (p = 0.02). The ETM did not induce respiratory muscle fatigue. ConclusionsExercising with the ETM appears to decrease exercise performance, in part, by increasing the sensation of dyspnea.

Transcutaneous vagal nerve stimulation effects on the salience network in patients with amnestic mild cognitive impairment

AbstractBackgroundBetter treatments are needed to improve cognition and reduce the disability associated with MCI and Alzheimer’s disease (AD). Transcutaneous vagal nerve stimulation (tVNS) may impact brain networks relevant to AD through multiple mechanisms: the vagus projects to the nucleus tractus solitarius (NTS) which in turn projects to the locus coeruleus (LC), the brain’s primary source of norepinephrine (NE). The NTS also projects directly to the hippocampus, as does the LC. Neuropathological data suggest that the LC may be an early site of AD pathology. Thus, tVNS may modify the activity of several networks that are impaired and that progressively deteriorate in patients with MCI and AD.Method24 patients with mild cognitive impairment (MCI) confirmed via diagnostic consensus conference (sources of info: Montreal Cognitive Assessment Test [MOCA], Clinical Dementia Rating scale (CDR), Functional Activities Questionnaire (FAQ) , Hopkins Verbal Learning Test – Revised [HVLT‐R] and medical record review) were assessed during rest using functional magnetic resonance imaging (fMRI) on a Siemens 3T scanner during tVNS (left tragus, n = 12) or under sham control conditions (ear lobe, n = 12).ResultDuring unilateral left tVNS, patients with MCI showed increased functional connectivity between nodes of the salience network, the anterior cingulate, and the supramarginal gyrus from both the right and left temporal poles.ConclusionIn patients with MCI, tVNS modified cognitively relevant brain networks whose degeneration predicts deterioration in AD. These findings demonstrate afferent target engagement of tVNS which carries implications for noninvasive therapeutic intervention in this population.

Music attenuates a widened central pulse pressure caused by resistance exercise: A randomized, single-blinded, sham-controlled, crossover study

Increasing central blood pressure is an independent predictor of cardiovascular disease and is an acute effect of high-intensity resistance exercise. It has been shown that classical music suppresses increased peripheral pressure during exercise. We hypothesized that classical music would suppress increased central pressure induced by high-intensity resistance exercise. To confirm this hypothesis, we examined the effect of classical music on central pressure following high-intensity resistance exercise in 18 young men. A randomized, single-blinded, sham-controlled, crossover trial was conducted under parallel experimental conditions on four separate days. The order of experiments was randomized between sham control (seated rest), music (20-min classical music track compilation), resistance exercise (5 sets of 10 repetitions at 75% of 1 repetition maximum), and resistance exercise with music conditions. Aortic pressure was measured in all subjects. No significant interaction between time, music, and resistance exercise was observed for aortic systolic pressure and diastolic pressure. In contrast, aortic pulse pressure showed a significant interaction; that is, aortic pulse pressure significantly widened after resistance exercise, whereas music significantly attenuated this widening. No significant change was observed in aortic pulse pressure in sham control and music conditions. The present findings suggest that music attenuates resistance exercise-induced increase in central pressure.

Dry Cupping Therapy for Improving Nonspecific Neck Pain and Subcutaneous Hemodynamics.

Dry cupping therapy is a noninvasive treatment commonly used to reduce pain and promote the healing process in various populations, including those with nonspecific neck pain; however, no data are available to support most of this method's true physiological benefits. To determine if dry cupping therapy decreased pain and increased subcutaneous blood flow compared with sham cupping and control conditions. Controlled laboratory study. Laboratory. A total of 32 participants (age = 22.5 ± 2.8 years, height = 173.3 ± 10.1 cm, mass = 76.6 ± 18.7 kg) with self-reported nonspecific neck pain. We used dry cupping and sham cupping interventions and a control condition. For the dry cupping intervention, 1 stationary cup was placed directly over the most painful area for 8 minutes. The sham cupping intervention followed the same procedures as the dry cupping intervention except a sham cup was applied. For the control condition, participants received no treatment. Subjective pain intensity (visual analog scale); pain-pressure threshold; subcutaneous hemodynamics, including superficial and deep oxygenated, deoxygenated, and total hemoglobin levels; and tissue saturation index. We observed differences in the visual analog scale score and the superficial and deep oxygenated and total hemoglobin levels (P values ≤ .002) immediately postintervention compared with baseline. Post hoc tests revealed that the dry cupping group had less pain than the sham cupping and control groups and higher superficial and deep oxygenated and total hemoglobin levels (P values ≤ .008). No differences were found between baseline and 24 hours postintervention. A single session of dry cupping therapy may be an effective short-term treatment method for immediately reducing pain and increasing oxygenated and total hemoglobin levels in patients with nonspecific neck pain.

Impact of tDCS and HD-tDCS on tinnitus perception: A scoping review.

Tinnitus is the auditory phantom perception of a sound that severely affects the quality of life of over 300,000 people in the United Kingdom alone. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation tool, which has been investigated as a potential tinnitus management option since 2006. This study aimed to investigate the impact of tDCS and high-definition transcranial direct current stimulation (HD-tDCS) on tinnitus perception. A scoping review was undertaken using the framework by Arksey and O'malley (2005). After consideration of relevance, 38 primary research studies were included in the data charting to examine the impact of (HD-)tDCS on tinnitus. Twenty-two of the primary research studies reported significant therapeutic effects of (HD)-tDCS on tinnitus perception. However, only eight of these included a sham-control condition. The tDCS protocols in the studies were highly heterogeneous and sample sizes were generally small. More double-blind, sham-controlled trials are needed that use similar protocols and outcome measures before definitive conclusions about the efficacy of (HD-)tDCS for tinnitus can be drawn.

Randomized, Sham-Controlled Trial of Real-Time Functional Magnetic Resonance Imaging Neurofeedback for Tics in Adolescents With Tourette Syndrome

BackgroundActivity in the supplementary motor area (SMA) has been associated with tics in Tourette syndrome (TS). The aim of this study was to test a novel intervention—real-time functional magnetic resonance imaging neurofeedback from the SMA—for reduction of tics in adolescents with TS. MethodsTwenty-one adolescents with TS were enrolled in a double-blind, randomized, sham-controlled, crossover study involving two sessions of neurofeedback from their SMA. The primary outcome measure of tic severity was the Yale Global Tic Severity Scale administered by an independent evaluator before and after each arm. The secondary outcome was control over the SMA assessed in neuroimaging scans, in which subjects were cued to increase/decrease activity in SMA without receiving feedback. ResultsAll 21 subjects completed both arms of the study and all assessments. Participants had significantly greater reduction of tics on the Yale Global Tic Severity Scale after real neurofeedback as compared with the sham control (p < .05). Mean Yale Global Tic Severity Scale Total Tic score decreased from 25.2 ± 4.6 at baseline to 19.9 ± 5.7 at end point in the neurofeedback condition and from 24.8 ± 8.1 to 23.3 ± 8.5 in the sham control condition. The 3.8-point difference is clinically meaningful and corresponds to an effect size of 0.59. However, there were no differences in changes on the secondary measure of control over the SMA. ConclusionsThis first randomized controlled trial of real-time functional magnetic resonance imaging neurofeedback in adolescents with TS suggests that this neurofeedback intervention may be helpful for improving tic symptoms. However, no effects were found in terms of change in control over the SMA, the hypothesized mechanism of action.

Reward motivation and neurostimulation interact to improve working memory performance in healthy older adults: A simultaneous tDCS-fNIRS study

Several studies have evaluated the effect of anodal transcranial direct current stimulation (tDCS) over the prefrontal cortex (PFC) for the enhancement of working memory (WM) performance in healthy older adults. However, the mixed results obtained so far suggest the need for concurrent brain imaging, in order to more directly examine tDCS effects. The present study adopted a continuous multimodal approach utilizing functional near-infrared spectroscopy (fNIRS) to examine the interactive effects of tDCS combined with manipulations of reward motivation. Twenty-one older adults (mean age = 69.7 years; SD = 5.05) performed an experimental visuo-spatial WM task before, during and after the delivery of 1.5 mA anodal tDCS/sham over the left prefrontal cortex (PFC). During stimulation, participants received performance-contingent reward for every fast and correct response during the WM task. In both sessions, hemodynamic activity of the bilateral frontal, motor and parietal areas was recorded across the entire duration of the WM task. Cognitive functions and reward sensitivity were also assessed with standard measures. Results demonstrated a significant impact of tDCS on both WM performance and hemodynamic activity. Specifically, faster responses in the WM task were observed both during and after anodal tDCS, while no differences were found under sham control conditions. However, these effects emerged only when taking into account individual visuo-spatial WM capacity. Additionally, during and after the anodal tDCS, increased hemodynamic activity relative to sham was observed in the bilateral PFC, while no effects of tDCS were detected in the motor and parietal areas. These results provide the first evidence of tDCS-dependent functional changes in PFC activity in healthy older adults during the execution of a WM task. Moreover, they highlight the utility of combining reward motivation with prefrontal anodal tDCS, as a potential strategy to improve WM efficiency in low performing healthy older adults.