Visual–vestibular interaction during goal directed locomotion: effects of aging and blurring vision

Normal vision overrides perturbed vestibular information for the optimization of performance during goal directed locomotion, suggesting down-regulation of vestibular gain. However, it is not known if the responses to vestibular perturbation are accentuated when vision is impaired. Furthermore, both visual and vestibular systems deteriorate with age. It is not clear, however, how age-related decline in these sensory systems influences visual–vestibular interaction. Therefore, the dual purpose of the present study was to investigate the effects of aging and blurring vision, that simulated the consequences of cataracts, on visual–vestibular interaction. Young and healthy elderly walked to a target located straight ahead with either normal or blurring vision. On randomly selected trials vestibular system perturbation was achieved by applying transmastoidal galvanic vestibular stimulation (GVS). Two different galvanic stimulation intensities were used to provide insight into scaling effect of vestibular perturbation on locomotor performance and how age and vision influences this scaling effect. Maximum path deviation, frontal trunk tilt and postural coordination in the mediolateral direction were evaluated. The magnitude of the path deviation and the trunk tilt response were scaled to the magnitude of the vestibular perturbation in older adults independent of the visual condition. Older participants demonstrated increased coupling of the head and trunk segments irrespective of visual and vestibular perturbations. The results suggest that when visual information was available, the vestibular input reweighting was less effective in older individuals, as shown by the scaled responses to the GVS intensities and the inability to converge efficiently towards the target.     

Intersegmental coordination during human locomotion: does planar covariation of elevation angles reflect central constraints?

To study intersegmental coordination in humans performing different locomotor tasks (backward, normal, fast walking, and running), we analyzed the spatiotemporal patterns of both elevation and joint angles bilaterally in the sagittal plane. In particular, we determined the origins of the planar covariation of foot, shank, and thigh elevation angles. This planar constraint is observable in the three-dimensional space defined by these three angles and corresponds to the plane described by the three time-varying elevation angle variables over each step cycle. Previous studies showed that this relation between elevation angles constrains lower limb coordination in various experimental situations. We demonstrate here that this planar covariation mainly arises from the strong correlation between foot and shank elevation angles, with thigh angle independently contributing to the pattern of intersegmental covariation. We conclude that the planar covariation of elevation angles does not reflect central constraints, as previously suggested. An alternative approach for analyzing the patterns of coordination of both elevation and joint (hip, knee, and ankle) angles is used, based on temporal cross-correlation and phase relationships between pairs of kinematic variables. We describe the changes in the pattern of intersegmental coordination that are associated with the changes of locomotor modes and locomotor speeds. We provide some evidence for a distinct control of thigh motion and discuss the respective contributions of passive mechanical factors and of active (arising from neural control) factors to the formation and the regulation of the locomotor pattern throughout the gait cycle.     

Dynamic force responses of skeletal muscle during stretch–shortening cycles

Muscle damage due to stretch–shortening cycles (i.e., cyclic eccentric/concentric muscle actions) is one of the major concerns in sports and occupational related activities. Mechanical responses of whole muscle have been associated with damage in neural motor units, in connective tissues, and the force generation mechanism. The objective of this study was to introduce a new method to quantify the real-time changes in skeletal muscle forces of rats during injurious stretch–shortening cycles. Male Sprague Dawley rats (n=24) were selected for use in this study. The dorsi flexor muscle group was exposed to either 150 stretch–shortening cycles (n=12) or 15 isometric contractions (n=12) in vivo using a dynamometer and electrical stimulation. Muscle damage after exposure to stretch–shortening cycles was verified by the non-recoverable force deficit at 48 h and the presence of myofiber necrosis. Variations of the dynamic forces during stretch–shortening cycles were analyzed by decomposing the dynamic force signature into peak force (F_peak), minimum force (F_min), average force (F_mean), and cyclic force (F_a). After the 15th set of stretch–shortening cycles, the decrease in the stretch–shortening parameters, F_peak, F_min, F_mean, and F_a, was 50% (P<0.0001), 26% (P=0.0055), 68% (P<0.0001), and 50% (P<0.0001), respectively. Our results showed that both isometric contractions and stretch–shortening cycles induce a reduction in the isometric force. However, the force reduction induced by isometric contractions fully recovered after a break of 48 h while that induced by stretch–shortening cycles did not. Histopathologic assessment of the tibialis anterior exposed to stretch–shortening cycles showed significant myofiber degeneration and necrosis with associated inflammation, while muscles exposed to isometric contractions showed no myofiber degeneration and necrosis, and limited inflammation. Our results suggest that muscle damage can be identified by the non-recoverable isometric force decrement and also by the variations in the dynamic force signature during stretch–shortening cycles.     

Low-frequency tuning in the human vestibular–ocular projection is determined by both peripheral and central mechanisms

We recently reported that a major contribution to the low-frequency tuning and sensitivity of the human vestibular system is the biomechanical properties of the vestibular end-organs. In the current paper, we investigate the contribution of additional mechanisms to low-frequency tuning. We compared the response properties of the vestibular system in 6 human volunteers to trains of 2 ms pulses of sound and transmastoid vibration using pulse repetition frequencies of 12.5, 25, 50, 100, 200 and 400 Hz. Measurements were made using two separate pathways arising from the vestibular apparatus: to the neck using vestibular evoked myogenic potentials (VEMPs), and to the eyes using ocular vestibular evoked myogenic potentials (OVEMPs). For both sound and vibration the two response pathways produced different tuning to pulse trains. The vestibulo-ocular pathway was characterised by a band-pass tuning with best frequency of 100 Hz whereas the vestibulo-collic pathway showed a peak at 400 Hz with sound only. These results suggest that properties of the vestibulo-ocular pathway also contribute to the low-frequency tuning that occurs for the OVEMP, in addition to previously reported end-organ effects.     

The force–velocity relationship of the human soleus muscle during submaximal voluntary lengthening actions

In experiments on isolated animal muscle, the force produced during active lengthening contractions can be up to twice the isometric force, whereas in human experiments lengthening force shows only modest, if any, increase in force. The presence of synergist and antagonist muscle activation associated with human experiments in situ may partly account for the difference between animal and human studies. Therefore, this study aimed to quantify the force–velocity relationship of the human soleus muscle and assess the likelihood that co-activation of antagonist muscles was responsible for the inhibition of torque during submaximal voluntary plantar flexor efforts. Seven subjects performed submaximal voluntary lengthening, shortening(at angular, velocities of +5, –5, +15, –15 and +30, and –30° s^–1) and isometric plantar flexor efforts against an ankle torque motor. Angle-specific (90°) measures of plantar flexor torque plus surface and intramuscular electromyography from soleus, medial gastrocnemius and tibialis anterior were made. The level of activation (30% of maximal voluntary isometric effort) was maintained by providing direct visual feedback of the soleus electromyogram to the subject. In an attempt to isolate the contribution of soleus to the resultant plantar flexion torque, activation of the synergist and antagonist muscles were minimised by: (1) flexing the knee of the test limb, thereby minimising the activation of gastrocnemius, and (2) applying an anaesthetic block to the common peroneal nerve to eliminate activation of the primary antagonist muscle, tibialis anterior and the synergist muscles, peroneus longus and peroneus brevis. Plantar flexion torque decreased significantly (P<0.05) after blocking the common peroneal nerve which was likely due to abolishing activation of the peroneal muscles which are synergists for plantar flexion. When normalised to the corresponding isometric value, the force–velocity relationship between pre- and post-block conditions was not different. In both conditions, plantar flexion torques during shortening actions were significantly less than the isometric torque and decreased at faster velocities. During lengthening actions, however, plantar flexion torques were not significantly different from isometric regardless of angular velocity. It was concluded that the apparent inhibition of lengthening torques during voluntary activation is not due to co-activation of antagonist muscles. Results are presented as mean (SEM).     

Interlimb coupling from the arms to legs is differentially specified for populations of motor units comprising the compound H-reflex during “reduced” human locomotion

Recent experiments have identified neuromechanical interactions between the arms and legs during human locomotor movement. Previous work reported that during the rhythmic movement of all four limbs, the influence of the arms on reflex expression in the legs was superimposed on the dominant effect of the legs. This evidence was based upon studies using cutaneous and H-reflex modulation as indices of neuronal activity related to locomotion. The earlier H-reflex study was restricted to one phase of movement and to only a fixed H-reflex amplitude. Also, all four limbs were actively engaged in locomotor movement, and this led to the speculation that the effect from the arms could be underestimated by “swamping” of the conditioning during movement of the test limb. Work from the cat suggests that descending locomotor drive may be differentially specified for different motor unit populations in the hindlimb. Accordingly, details of interlimb coordination between the arms and legs in humans require further characterization and an examination of different populations of motor units as can be obtained from H-reflex recruitment curve (RC) parameters. Using modulation of H-reflex amplitudes across the entire ascending limb as neural probes for interlimb coupling, the present study evaluated the separated influences of rhythmic activity of the arms and leg on neuronal excitability of a stationary “test leg”. This three-limb “reduced” locomotion approach was applied using a stepping ergometer during the performance of three rhythmic movement tasks: arms (A); contralateral leg (L); and arms and contralateral leg (AL). Data were sampled at four different phases of the stepping cycle (using the moving leg as reference): start power (SP); end power (EP); start recovery (SR); and end recovery (ER). The main result was a large and significant influence of rhythmic AL activity on RC parameters of the H-reflex at EP and SP phases. However, the parameters (and thus motor unit populations) were differentially affected at each phase and task. For instance, a significant contribution of arms movement was noticed for H _max (largest motor units) at EP phase (P < 0.05), but no changes was observed for other parameters related to lower reflex amplitude (e.g., H-reflex evoked with an input that elicited 50% of maximum reflex response during static condition; H@50%). On the other hand, at SR phase, the parameter H@50% was significantly affected during AL compared to L. It is suggested that the remote effect from arms rhythmic activity has been differentially manifested across motor unit populations for each phase of movement. These findings provide definitive evidence for interlimb coupling between cervical and lumbar oscillators in gating the excitability of reflex pathways to a leg muscle for different populations of motorneurons within the pool. This further supports the contention of similar functional organization for locomotor networks in the human when compared to other animals. Additionally, these data provide additional confirmation of the significant role of the output of neural control for rhythmic arm movement in modulating reflex excitability of the legs that is specifically adjusted according to the phase and task.     

Brain oscillatory 4–35 Hz EEG responses during an n-back task with complex visual stimuli

Brain oscillatory responses of 4–35 Hz EEG frequencies elicited during performance of a visual n-back task with complex visual stimuli were assessed in 20 adult volunteers. Spectral power changes were assessed separately for target and non-target stimuli in four different memory load conditions (0, 1, 2, and 3-back). The presentation of both target and non-target stimuli elicited long-lasting ∼4–8 Hz power increases, which were more prominent at the beginning of stimulus onset during presentation of target stimuli, as compared to non-target stimuli, in the 0-back memory load condition. ∼8–25 Hz power decreases appeared at stimulus onset. These power decreases were more prominent during the presentation of target stimuli, as compared to non-target stimuli, and their duration increased as a function of memory load between the 0-, 1-, and 2-back, but not the 3-back, memory load conditions. The current results provide further evidence in support of the notion of a complex interplay between both ∼4–8 Hz power increases and ∼8–25 Hz power decreases during cognitive memory task performance.     

A 3D reconstruction of pancreas development in the human embryos during embryonic period (Carnegie stages 15–23)

Aims  

The goal in this paper was to rebuild a three dimensional (3D) reconstruction of the dorsal and ventral pancreatic buds, in the human embryos, at Carnegie stages 15–23.     

Low incidence of human coronavirus among hospitalized children in Novosibirsk city,Russia during pre-pandemic period (2013–2020)

We investigated the incidence of 15 respiratory viruses among 2991 children with acute respiratory infections in Novosibirsk city, Russia, prior to the COVID-19 pandemic (2013–2020). Viral infections were detected in 72.5% cases. The incidence of human coronavirus was 2% (Alphacoronaviruses, 63%; Betacoronaviruses, 37%).     

Novel first-dose adverse drug reactions during a phase I trial of olipudase alfa (recombinant human acid sphingomyelinase) in adults with Niemann–Pick disease type B (acid sphingomyelinase deficiency)

PurposeEnzyme replacement therapy with olipudase alfa (recombinant human acid sphingomyelinase) is being developed for Niemann–Pick disease type B (NPD B).MethodsA single-center, open-label, nonrandomized, single-ascending-dose trial evaluated the safety of intravenous olipudase alfa (0.03–1.0 mg/kg) in 11 adults with NPD B. Patients were monitored in the hospital for 72 h after infusion and had follow-up visits on days 14 and 28.ResultsPlasma ceramide, a product of sphingomyelin catabolism by olipudase alfa, showed dose-dependent elevations by 6 h postdose, or postinfusion. No serious adverse drug reactions (ADRs) occurred during the study. Acute phase reaction-type ADRs, as evidenced by elevated inflammatory biomarkers (high-sensitivity C-reactive protein, interleukin-8, and calcitonin) and constitutional symptoms (fever, pain, nausea, and/or vomiting) emerged 12–24 h following doses ≥0.3 mg/kg olipudase alfa. Three patients experienced hyperbilirubinemia. The study was terminated after a patient dosed at 1 mg/kg exhibited severe hyperbilirubinemia; he was subsequently diagnosed with Gilbert syndrome.ConclusionThe maximum tolerated dose of olipudase alfa in adults with NPD B was 0.6 mg/kg. First-dose ADRs were likely induced by elevated concentrations of ceramide (or its downstream derivatives) generated by the catabolism of accumulated sphingomyelin. Within-patient dose escalation to slowly catabolize sphingomyelin stores may be a strategy to mitigate first-dose ADRs in patients with NPD B.     

Molecular characterization of group A human rotaviruses in Bangkok and Buriram,Thailand during 2004–2006 reveals the predominance of G1P[8], G9P[8] and a rare G3P[19] strain

The aim of this study has been to determine the incidence of diverse human rotavirus strains circulating in Thailand between October 2004 and April 2006 by means of molecular characterization. Pediatric patients aged between 2 months and 5 years diagnosed with acute diarrhea (n = 307) in Bangkok and Buriram, Thailand were tested for human rotavirus A (RV-A) by RT-PCR. A total of 130 specimens (42.3%) were found RV-A positive and 126 were characterized by direct sequencing of the capsid glycoproteins VP7 and VP4. BLAST/FASTA analysis and phylogenetic analysis revealed genotypes G1P[8] (85.7%), G2P[4] (2.4%), G2P[8] (0.8%), G3P[8] (1.6%), G9P[8] (8.7%), and the uncommon strain G3P[19] (0.8%). Varying sites of polymorphism over time imply dependence on geographical location along with seasonal variation of relative incidence and distribution of rotavirus types. Thus, continuous molecular monitoring of human rotavirus epidemiology is essential for adjusting vaccine development.