Experimental Physiology最新文献

Context-dependent sensory processing within the predictive coding framework relies on detecting mismatches between incoming stimuli and internal predictive models. Sensory deviants elicit prediction errors, seen as enhanced neural responses, that update these models and influence attention and behaviour. Although prediction errors have been widely observed across brain regions, the downstream processes remain poorly understood. In this study, we recorded electrocorticography in five urethane-anaesthetised rats and identified cortical slow oscillations, characterised by spontaneous transitions between 'Up' and 'Down' states. Deviant stimuli in an auditory oddball paradigm evoked an initial positive prediction error, followed by a prolonged, all-or-nothing response which spread in a travelling wave across the cortex. Identified as putative evoked cortical Up states, these responses were not evoked by standards, omissions or a many-standards control. Up states following deviants occurred more recently after a previous Up state when compared to spontaneous Up states. In preliminary data from an awake rat, long-latency Up states were not present spontaneously or evoked. In a different rat, anaesthetic depth was key to spontaneous and evoked Up states, with more robust Up/Down states and more reliable triggering of Up states under deeper anaesthesia. These results suggest that sensory deviants may cause shifts in cortical state under anaesthesia, explaining the long-latency mismatch response under anaesthesia and sleep.

Consumption of a high-sugar mixed meal (HSMM) increases both glucose and insulin and elicits mixed vascular effects, with reduced microvascular blood flow but increased conduit artery diameter and blood flow. In this study, we sought to examine: (1) whether an HSMM elicits vascular segment-specific effects within cerebrovasculature; and (2) whether these responses differ between young healthy adults and middle-aged adults with cardiometabolic disease (CMD) risk factors. Twenty-one young, healthy adults (ages 18-39 years; 24 ± 6 years) and 20 middle-aged adults (ages 40-65 years; 55 ± 5 years) with CMD risk factors (hypertension, obesity or dyslipidaemia) underwent cerebrovascular assessments before and at 30 and 60 min after a 930 kcal HSMM. Carotid and aortic stiffness and carotid artery characteristic impedance were assessed via ultrasound and tonometry. Middle cerebral artery mean velocity, pulsatility index and resistive index were assessed via transcranial Doppler. In comparison to baseline, common carotid artery diameter increased while stiffness decreased, contributing to a decrease in carotid artery characteristic impedance in both groups following the HSMM (p < 0.05). In comparison to baseline, middle cerebral artery mean velocity, pulsatility index and resistive index increased only in young adults (p < 0.05) following the HSMM. Differential increases in cerebral pulsatility among young adults compared with middle-aged adults with CMD risk factors might reflect modest differences in upstream, extracranial artery pulsatile transmission following an HSMM, along with simultaneous, complex intracranial cerebrovascular responses that require further interrogation. Cumulatively, these data suggest that: (1) the cerebrovascular response to an HSMM might differ between segments of the extra- versus intracranial cerebrovasculature; and (2) middle-aged adults with CMD risk factors might have altered cerebrovascular responsiveness to an HSMM compared with young, healthy adults.

Endothelial dysfunction drives obesity-related complications. Doppler ultrasound measurement of blood flow during 1-min passive leg movements (PLM) is a valuable non-invasive tool for assessing endothelial function and nitric oxide (NO)-mediated vasodilation. The objectives of this work were t o identify endothelial dysfunction biomarkers in young individuals with obesity (OB) using the PLM test; to evaluate the effects of a rehabilitation programme on these biomarkers; and to explore associations between PLM data, oxidative metabolism and blood biomarkers of microvascular impairment. Fifteen male OB (age 17 ± 4 years; body mass 121.4 ± 24.1 kg; body mass index 39.3 ± 7.5 kg m^-2) were tested before (PRE) and after (POST) a 3-week multidisciplinary body mass reduction programme. Fifteen age-matched normal-weight males (CTRL) underwent PRE measurements. Participants performed an incremental exercise, a PLM test and underwent blood biomarker analysis. Peak oxygen uptake and ventilatory thresholds (mL kg^-1 min^-1) were ∼40% lower in OB versus CTRL (P < 0.001) and improved by ∼8% in OB POST versus PRE (P < 0.05). Plasma nitrite concentration was lower in OB (0.18 ± 0.09 µmol L^-1) versus CTRL (0.51 ± 0.49; P = 0.02). Baseline blood flow, normalized for appendicular muscle mass, was similar between the two groups, whereas peak blood flow, Δpeak (difference between peak and baseline) and the area under the blood flow versus time curve were significantly lower in OB PRE, with improvements in OB POST. Several blood biomarkers of endothelial barrier function and permeability differed in OB versus CTRL. The blunted PLM-induced hyperaemic response and lower plasma nitrite levels indicate impaired endothelial function in young individuals with obesity, occurring before the onset of cardiovascular and metabolic complications.

The aim of the study was to investigate the spinal mechanisms involved in regulating postural balance in humans. Participants stood in a normal stance, with their spinal postural networks either non-invasively activated or not stimulated by electrical stimulation. Postural sway, muscle activity, joint kinematics and respiratory movements were monitored. Half of the participants depended on external sensory cues for controlling balance (field dependent), whereas the other half did not (field independent). Stimulation was performed at the T11-T12 or L1-L2 vertebral level using intensities below the motor threshold. When participants stood without stimulation, differences in body segment movement in the frontal plane were observed between subgroups, in addition to similarities in segment movement in the sagittal plane. Field-dependent participants demonstrated greater mediolateral sway and pelvic motion and relied more on hip involvement in frontal centre of pressure dynamics than field-independent participants. Stimulation at T11-T12 induced changes in muscle activity and body segment coordination in both groups. It led to a reduction in mediolateral sway and enhanced postural stability, but only in field-dependent individuals. Stimulation at L1-L2 altered muscle activity and joint kinematics in both subgroups without having an effect on postural stability. Stimulation did not affect respiratory movements or posture-respiratory coupling. In the human spinal cord, the interneuronal networks involved in postural regulation are located at the T11-T12 level and operate under supraspinal control. Interneuronal networks at the L1-L2 level also modulate muscle activity and body segment coordination; however, their specific role in regulating upright posture remains unclear.

The dynamics of physiological systems are impacted by both exercise and hypoxia. Network models can be used to map the interactions between various physiological components in environmental physiology and exercise using the concepts of information theory. This cross-over study compared three normobaric conditions: control, simulated altitude of 2500 m (fraction of inspired oxygen: $F_{i{O}_2}$ ≈ 15.1%) and 3500 m ( $F_{i{O}_2}$ ≈ 13.5%), and rest vs. isometric exercise through the lens of network physiology. The 12 participants (6 M and 6 F; 22.25 ± 2.42 years; 23.01 ± 3.24 kg/m²) spent ∼30 min in a tent coupled to an altitude simulator, whose last 3 min consisted of a series of nine unilateral isometric maximal contractions of quadriceps. A metabolic system in breath-by-breath mode was used to register cardiorespiratory variables. In-degree, out-degree, and transfer entropy (TE) were computed to capture the information flow between variables. A weighted Jaccard Similarity Index was used to assess network similarities. The increase of ${\dot{V}}_{O_2}$ in exercise over rest was slightly more prominent during hypoxia (P = 0.054, η² _p = 0.232). Normoxia-hypoxia networks were more similar during resting than exercise. Rest-exercise networks were less similar to each other during simulated altitude of ∼2500 m (P = 0.008, η² _p = 0.353). Neither TE during rest nor during exercise nor the $S_{p{O}_2}$ / $F_{i{O}_2}$ ratio significantly predicted the occurrence of symptoms. Unexpectedly, compared to mild-grade hypoxia, low-grade hypoxia induced more changes in physiological connectivity, with the majority of the connections converging on putative hidden nodes that we suggest are oxygen delivery-dependent. Network approaches could offer new developments in exercise and environmental physiology.

There is a category of large-scale neuromusculoskeletal injuries that result in long-term functional disabilities, and one such injury is volumetric muscle loss (VML) injury. In addition to the clinical outcomes related to long-term dysfunction, co-morbidities and reduced mobility and physical activity, this review addresses several underexplored physiological limitations of VML at both the whole-body level and within the injured muscle. Our objectives with this review are to provide: (1) critical understanding of the pathophysiological limitations related to VML injury; (2) evidence for emerging treatment options that target the VML-induced metabolic dysregulation; and (3) early functional data on metabolic treatments as a component of regenerative rehabilitation. We highlight new attempts to intervene in this unique pathophysiology, in addition to current unanswered questions for the field.

Recanalization by endovascular treatment (EVT) is effective in acute ischaemic stroke caused by large-vessel occlusion. Better understanding of the pathophysiology could possibly identify targets for improving peri-procedural management and thereby patient outcome. Dynamic cerebral autoregulation (dCA), which maintains cerebral blood flow despite changes in arterial blood pressure (ABP), is reportedly impaired after EVT. Blood pressure thresholds after EVT have previously been individualized by accounting for dCA, which could improve outcome. The conventional method to estimate dCA requires transcranial Doppler, which is difficult to use during EVT. Instead, we investigated dCA during EVT by near-infrared spectroscopy (NIRS) which is more feasible. NIRS and ABP were measured continuously before recanalization, immediately after recanalization, and after general anaesthesia termination for subsequent transfer function analysis yielding the dCA measure of phase shift (0.07-0.2 Hz). Phase shift did not differ between the ischaemic and contralateral hemisphere but the sensitivity to end-tidal CO₂ was increased in the ischaemic hemisphere immediately after recanalization. Phase shift over time interacted with 90-day functional outcome including independence and mortality. Hence, patients with good long-term outcome showed increased phase shift during and after EVT, while phase shift decreased in poor outcome patients. In conclusion, dCA did not differ between hemispheres during EVT but was more sensitive to end-tidal CO₂ in the ischaemic compared to the contralateral hemisphere and dCA evolved differently in patients with good and poor outcome. Our findings of individual dCA differences during EVT suggest benefit of individualized blood pressure management, which should be addressed in future studies.

Skeletal muscle plays an important role in whole-body health, quality of life and regulation of metabolism. The maintenance of a healthy mitochondrial pool is imperative for the preservation of skeletal muscle quality and is mediated through mitochondrial quality control consisting of mitochondrial turnover mediated by a balance between organelle synthesis and degradation. The selective tagging and removal of dysfunctional mitochondria is essential for maintaining mitochondrial quality control and is termed mitophagy. The mechanisms of the initial stages of mitophagy involving the recognition and tagging of mitochondria within skeletal muscle are well established, but our understanding of the terminal step involving organelle degradation mediated via lysosomes is in its infancy. An assessment of the proteolytic functions to facilitate the removal and breakdown of dysfunctional mitochondria is crucial for our understanding of the mechanisms of mitophagy, which is essential for maintaining skeletal muscle health. The aim of this review is to address the current knowledge surrounding mitophagy and lysosomal function, alongside distinct physiological conditions, such as ageing, exercise and disuse, that have varying effects on mitophagy and lysosomal adaptations within skeletal muscle.