Balance task and head orientation dependency of vestibular reflexes in neck muscles

Human upright posture of both the head and body is facilitated by the CNS’s ability to integrate multiple sensory feedback signals, as well as its discernibility of the motor commands that maintain this stabilization. The vestibular organ in particular detects motion of the head-in-space, which is transformed according to on-going head and body orientation into appropriate motor responses. However, when motor commands do not contribute to the control of standing posture, and are incongruent with their expected sensory consequences, vestibulomuscular responses in the lower limb undergo unconscious suppression. In this study, we investigated whether vestibular response suppression occurs in neck muscles under conditions where the muscles are active but not engaged in a task to balance the head. In addition, we examined the effects of head orientation to identify spatial transformation of vestibular reflex responses. Eight subjects were exposed to stochastic vestibular stimulation (0-75 Hz) in a seated condition while their head was either free or fixed, and rotated at either 0 or 60°. In head-free conditions, subjects were asked to rotate their head 60° to the left in order to activate agonist neck muscle pairs (sternocleidomastoid - SCM and splenius capitis - SPL). In head-fixed conditions, subjects performed isometric neck muscle contractions in yaw at orientations of 0° and 60°, as well as flexion, extension and co-contraction at an orientation of 0°. Intramuscular EMG was collected bilaterally in SCM and SPL muscles. Muscle responses correlated to the input stimuli were significant (P < 0.05) for all conditions provided the muscle was used in contraction. Neither muscle underwent the expected vestibulomuscular suppression when not engaged in the balance task (i.e. head-fixed). Nevertheless, the magnitude of the SPL responses decreased by 22% when the head was fixed whereas SCM responses were unaffected. The effect of head fixation only in SPL suggests differences in neural pathways across muscles, possibly via alternative pathways known to exist in the SPL from the well-established monosynaptic vestibulospinal inputs in SCM and SPL. For both muscles, the effect of orientation and force direction had no effect on muscles responses. Since the stimulation is fixed relative to the head, the same muscles are activated to respond to the input stimulus at both orientations and all force directions. These results indicate that the vestibular pathways connecting neck muscles are less susceptible to suppression than lower limb muscles, most likely because the monosynaptic inputs innervating them are subject to less central control

Vestibular contributions to lateral stabilization are bilaterally dependent during split belt walking

Vestibular information is critical for maintaining balance during locomotion, and is known to be attenuated with increasing locomotor velocity and cadence. This attenuation is muscle and phase dependent, and is thought to reflect the functional contribution of each muscle to balance control during each stride of the gait cycle. Bilaterally, the vestibular coupling is mirrored relative to the gait cycle as each leg undergoes similar modulation with variation in phase, velocity and cadence. Here, we asked whether the modulation of the vestibular contribution to each limb is bilaterally dependent. By using a split-belt treadmill with asymmetric belt speeds, we can control the locomotion properties of each leg and compare the vestibular modulation to symmetric conditions. We hypothesized that bilaterally symmetric vestibular modulation would indicate leg independent vestibular influence while bilaterally asymmetric vestibular modulation would indicate leg dependent vestibular influence. Subjects were exposed to binaural bipolar stochastic vestibular stimulation (0-25 Hz) during symmetric and asymmetric walking conditions. Symmetric trials were performed at belt speeds of 0.4 and 0.8 m/s and for 10 min. The asymmetric trial was performed at belt speeds of 0.4 and 0.8 m/s for 16 min. Subjects walked with a cadence of 78 steps/min which was easily maintained in both limbs. EMG of the bilateral medial gastrocnemii and three-dimensional ground reaction force and torques were collected. Only the last 340 strides (~ 9 min of data) were used in the analysis to avoid the adaptation that typically occurs within the first 250 strides (~ 6 min) of asymmetric walking. Significant muscle activity and lateral ground reaction forces (P < 0.01) were correlated to the input stimuli in all trials. Stimulus-EMG and -lateral ground reaction force correlations decreased at higher belt speeds during symmetric walking, as previously reported. During the split belt condition, the magnitude of correlations stimulus-EMG and -force were bilaterally asymmetric and different from their symmetric counterparts. During the asymmetric condition correlations decreased for the slow leg, but more closely resembled the responses observed during slow symmetric walking, and increased for the fast leg, but more closely resembled the responses observed during fast symmetric walking. These results indicate that the modulation of vestibular reflexes is dependent upon the specific kinematics of each leg but bilaterally linked to respond to the properties of the locomotion pattern

A task-relevant experimental pain model to target motor adaptation

Key points: Motor adaptation is thought to be a strategy to avoid pain. Current experimental pain models do not allow for consistent modulation of pain perception depending on movement. We showed that low-frequency sinusoidal stimuli delivered at painful intensity result in minimal habituation of pain perception (over 60 s) and minimal stimulation artefacts on electromyographic signals. When the amplitude of the low-frequency sinusoidal stimuli was modulated based on the vertical force participants applied to the ground with their right leg while standing upright, we demonstrated a strong association between perceived pain and motor adaptation. By enabling task-relevant modulation of perceived pain intensity and the recording electromyographic signals during electrical painful stimulation, our novel pain model will permit direct experimental testing of the relationship between pain and motor adaptation. Abstract: Contemporary pain adaptation theories predict that motor adaptation occurs to limit pain. Current experimental pain models, however, do not allow for pain intensity modulation according to one's posture or movements. We developed a task-relevant experimental pain model using low-frequency sinusoidal electrical stimuli applied over the infrapatellar fat pad. In fourteen participants, we compared perceived pain habituation and stimulation-induced artefacts in vastus medialis electromyographic recordings elicited by sinusoidal (4, 10, 20 and 50 Hz) and square electrical waveforms delivered at constant peak stimulation amplitude. Next, we simulated a clinical condition where perceived knee pain intensity is proportional to the load applied on the leg by controlling sinusoidal current amplitude (4 Hz) according to the vertical force the participants applied with their right leg to the ground while standing upright. Pain ratings habituated over a 60 s period for 50 Hz sinusoidal and square waveforms but not for low-frequency sinusoidal stimuli (P &lt; 0.001). EMG filters removed most stimulation artefacts for low-frequency sinusoidal stimuli (4 Hz). While balancing upright, participants’ pain ratings were correlated with the force applied by the right leg (R2 = 0.65), demonstrating task-relevant changes in perceived pain intensity. Low-frequency sinusoidal stimuli can induce knee pain of constant intensity for 60 s with minimal EMG artefacts while enabling task-relevant pain modulation when controlling current amplitude. By enabling task-dependent modulation of perceived pain intensity, our novel experimental model replicates key temporal aspects of clinical musculoskeletal pain while allowing quantification of neuromuscular activation during painful electrical stimulation. This approach will enable researchers to test the predicted relationship between movement strategies and pain. © 2021 The Authors. The Journal of Physiology © 2021 The Physiological Societ

Molecular characterisation of viruses from Kiwifruit

In 2003 Apple stem grooving virus was discovered in Actinidia accessions from China, being held in quarantine in Auckland. Subsequent examination of kiwifruit germplasm from the same source has detected several additional viruses, including a ~300 nm rigid rod related to Ribgrass mosaic virus (Tobamovirus), a 700-750 nm flexuous virus related to Citrus leaf blotch virus (Flexiviridae) and a novel vitivirus. Currently these viruses have not been reported from commercial kiwifruit crops in New Zealand or elsewhere. The biological properties of the viruses from kiwifruit and their phylogenetic relationships with similar viruses from other plants will be described, and the possible implications for the international movement of Actinidia germplasm are discussed

Lack of the transcription factor hypoxia-inducible factor (HIF)-1α in macrophages accelerates the necrosis of Mycobacterium avium-induced granulomas

Accepted ManuscriptThe establishment of mycobacterial infection is characterized by the formation of granulomas, which are well-organized aggregates of immune cells, namely, infected macrophages. The granuloma's main function is to constrain and prevent dissemination of the mycobacteria while focusing the immune response to a limited area. In some cases these lesions can grow progressively into large granulomas which can undergo central necrosis, thereby leading to their caseation. Macrophages are the most abundant cells present in the granuloma and are known to adapt under hypoxic conditions in order to avoid cell death. Our laboratory has developed a granuloma necrosis model that mimics the human pathology of Mycobacterium tuberculosis, using C57BL/6 mice infected intravenously with a low dose of a highly virulent strain of Mycobacterium avium. In this work, a mouse strain deleted of the hypoxia inducible factor 1a (HIF-1a) under the Cre-lox system regulated by the lysozyme M gene promoter was used to determine the relevance of HIF-1a in the caseation of granulomas. The genetic ablation of HIF-1a in the myeloid lineage causes the earlier emergence of granuloma necrosis and clearly induces an impairment of the resistance against M. avium infection coincident with the emergence of necrosis. The data provide evidence that granulomas become hypoxic before undergoing necrosis through the analysis of vascularization and quantification of HIF-1a in a necrotizing mouse model. Our results show that interfering with macrophage adaptation to hypoxia, such as through HIF-1a inactivation, accelerates granuloma necrosis.Support from national funds through FCT/MEC (Fundação para a Ciência e a Tecnologia/Ministério da Educação e Ciência), when applicable cofunded by FEDER funds within the partnership agreement PT2020 related to the research unit number 4293; from “NORTE-07-0124-FEDER-000002-Host-Pathogen Interactions,” cofunded by Programa Operacional Regional do Norte (ON.2–O Novo Norte), under the Quadro de Referência Estratégico Nacional (QREN); and from HMSP-ICT/0024/2010. T.M.S. received postdoctoral grant ON2201310 from “NORTE-07-0124-FEDER-000002-Host-Pathogen Interactions,” cofunded by Programa Operacional Regional do Norte (ON.2–O Novo Norte), under the Quadro de Referência Estratégico Nacional (QREN). M.R. received Ph.D. grant SFRH/BD/89871/2012 from FCT, Portuga

Electrical vestibular stimuli evoke robust muscle activity in deep and superficial neck muscles in humans

Neck muscle activity evoked by vestibular stimuli is a clinical measure for evaluating the function of the vestibular apparatus. Cervical vestibular-evoked myogenic potentials (cVEMP) are most commonly measured in the sternocleidomastoid muscle (and more recently the splenius capitis muscle) in response to air-conducted sound, bone-conducted vibration or electrical vestibular stimuli. It is currently unknown, however, whether and how other neck muscles respond to vestibular stimuli. Here we measured activity bilaterally in the sternocleidomastoid, splenius capitis, sternohyoid, semispinalis capitis, multifidus, rectus capitis posterior, and obliquus capitis inferior using indwelling electrodes in two subjects exposed to binaural bipolar electrical vestibular stimuli. All recorded neck muscles responded to the electrical vestibular stimuli (0-100 Hz) provided they were active. Furthermore, the evoked responses were inverted on either side of the neck, consistent with a coordinated contribution of all left-right muscle pairs acting as antagonists in response to the electrically-evoked vestibular error of head motion. Overall, our results suggest that, as previously observed in cat neck muscles, broad connections exist between the human vestibular system and neck motoneurons and highlight the need for future investigations to establish their neural connections

Quantitative backscattered electron imaging of bone using a thermionic or a field emission electron source

Quantitative backscattered electron imaging is an established method to map mineral content distributions in bone and to determine the bone mineralization density distribution (BMDD). The method we applied was initially validated for a scanning electron microscope (SEM) equipped with a tungsten hairpin cathode (thermionic electron emission) under strongly defined settings of SEM parameters. For several reasons, it would be interesting to migrate the technique to a SEM with a field emission electron source (FE-SEM), which, however, would require to work with different SEM parameter settings as have been validated for DSM 962. The FE-SEM has a much better spatial resolution based on an electron source size in the order of several 100 nanometers, corresponding to an about 105 to 106 times smaller source area compared to thermionic sources. In the present work, we compare BMDD between these two types of instruments in order to further validate the methodology. We show that a transition to higher pixel resolution (1.76, 0.88, and 0.57 μm) results in shifts of the BMDD peak and BMDD width to higher values. Further the inter-device reproducibility of the mean calcium content shows a difference of up to 1 wt% Ca, while the technical variance of each device can be reduced to ±0.17 wt% Ca. Bearing in mind that shifts in calcium levels due to diseases, e.g., high turnover osteoporosis, are often in the range of 1 wt% Ca, both the bone samples of the patients as well as the control samples have to be measured on the same SEM device. Therefore, we also constructed new reference BMDD curves for adults to be used for FE-SEM data comparison