The Neural Basis for Biased Behavioral Responses Evoked by Galvanic Vestibular Stimulation in Primates.

Noninvasive electrical stimulation of the vestibular system in humans has become an increasingly popular tool with a broad range of research and clinical applications. However, common assumptions regarding the neural mechanisms that underlie the activation of central vestibular pathways through such stimulation, known as galvanic vestibular stimulation (GVS), have not been directly tested. Here, we show that GVS is encoded by VIIIth nerve vestibular afferents with nonlinear dynamics that differ markedly from those predicted by current models. GVS produced asymmetric activation of both semicircular canal and otolith afferents to the onset versus offset and cathode versus anode of applied current, that in turn produced asymmetric eye movement responses in three awake-behaving male monkeys. Additionally, using computational methods, we demonstrate that the experimentally observed nonlinear neural response dynamics lead to an unexpected directional bias in the net population response when the information from both vestibular nerves is centrally integrated. Together our findings reveal the neural basis by which GVS activates the vestibular system, establish that neural response dynamics differ markedly from current predictions, and advance our mechanistic understanding of how asymmetric activation of the peripheral vestibular system alters vestibular function. We suggest that such nonlinear encoding is a general feature of neural processing that will be common across different noninvasive electrical stimulation approaches.SIGNIFICANCE STATEMENT Here, we show that the application of noninvasive electrical currents to the vestibular system (GVS) induces more complex responses than commonly assumed. We recorded vestibular afferent activity in macaque monkeys exposed to GVS using a setup analogous to human studies. GVS evoked notable asymmetries in irregular afferent responses to cathodal versus anodal currents. We developed a nonlinear model explaining these GVS-evoked afferent responses. Our model predicts that GVS induces directional biases in centrally integrated head motion signals and establishes electrical stimuli that recreate physiologically plausible sensations of motion. Altogether, our findings provide new insights into how GVS activates the vestibular system, which will be vital to advancing new clinical and biomedical applications.

Vestibular control of deep and superficial lumbar muscles.

The active control of the lumbar musculature provides a stable platform critical for postures and goal-directed movements. Voluntary and perturbation-evoked motor commands can recruit individual lumbar muscles in a task-specific manner according to their presumed biomechanics. Here, we investigated the vestibular control of the deep and superficial lumbar musculature. Ten healthy participants were exposed to noisy electrical vestibular stimulation while balancing upright with their head facing forward, left, or right to characterize the differential modulation in the vestibular-evoked lumbar extensor responses in generating multidirectional whole body motion. We quantified the activation of the lumbar muscles on the right side using indwelling [deep multifidus, superficial multifidus, caudal longissimus (L4), and cranial longissimus (L1)] and high-density surface recordings. We characterized the vestibular-evoked responses using coherence and peak-to-peak cross-covariance amplitude between the vestibular and electromyographic signals. Participants exhibited responses in all lumbar muscles. The vestibular control of the lumbar musculature exhibited muscle-specific modulations: responses were larger in the longissimus (combined cranio-caudal) compared with the multifidus (combined deep-superficial) when participants faced forward (P < 0.001) and right (P = 0.011) but not when they faced left. The high-density surface recordings partly supported this observation: the location of the responses was more lateral when facing right compared with left (P < 0.001). The vestibular control of muscle subregions within the longissimus or the multifidus was similar. Our results demonstrate muscle-specific vestibular control of the lumbar muscles in response to perturbations of vestibular origin. The lack of differential activation of lumbar muscle subregions suggests the vestibular control of these subregions is co-regulated for standing balance.NEW & NOTEWORTHY We investigated the vestibular control of the deep and superficial lumbar extensor muscles using electrical vestibular stimuli. Vestibular stimuli elicited preferential activation of the longissimus muscle over the multifidus muscle. We did not observe clear regional activation of lumbar muscle subregions in response to the vestibular stimuli. Our findings show that the central nervous system can finely tune the vestibular control of individual lumbar muscles and suggest minimal regional variations in the activation of lumbar muscle subregions.

Neural Mechanisms Underlying High-Frequency Vestibulocollic Reflexes In Humans And Monkeys.

The vestibulocollic reflex is a compensatory response that stabilizes the head in space. During everyday activities, this stabilizing response is evoked by head movements that typically span frequencies from 0 to 30 Hz. Transient head impacts, however, can elicit head movements with frequency content up to 300-400 Hz, raising the question whether vestibular pathways contribute to head stabilization at such high frequencies. Here, we first established that electrical vestibular stimulation modulates human neck motor unit (MU) activity at sinusoidal frequencies up to 300 Hz, but that sensitivity increases with frequency up to a low-pass cutoff of ∼70-80 Hz. To examine the neural substrates underlying the low-pass dynamics of vestibulocollic reflexes, we then recorded vestibular afferent responses to the same electrical stimuli in monkeys. Vestibular afferents also responded to electrical stimuli up to 300 Hz, but in contrast to MUs their sensitivity increased with frequency up to the afferent resting firing rate (∼100-150 Hz) and at higher frequencies afferents tended to phase-lock to the vestibular stimulus. This latter nonlinearity, however, was not transmitted to neck motoneurons, which instead showed minimal phase-locking that decreased at frequencies >75 Hz. Similar to human data, we validated that monkey muscle activity also exhibited low-pass filtered vestibulocollic reflex dynamics. Together, our results show that neck MUs are activated by high-frequency signals encoded by primary vestibular afferents, but undergo low-pass filtering at intermediate stages in the vestibulocollic reflex. These high-frequency contributions to vestibular-evoked neck muscle responses could stabilize the head during unexpected head transients.SIGNIFICANCE STATEMENT Vestibular-evoked neck muscle responses rely on accurate encoding and transmission of head movement information to stabilize the head in space. Unexpected transient events, such as head impacts, are likely to push the limits of these neural pathways since their high-frequency features (0-300 Hz) extend beyond the frequency bandwidth of head movements experienced during everyday activities (0-30 Hz). Here, we demonstrate that vestibular primary afferents encode high-frequency stimuli through frequency-dependent increases in sensitivity and phase-locking. When transmitted to neck motoneurons, these signals undergo low-pass filtering that limits neck motoneuron phase-locking in response to stimuli >75 Hz. This study provides insight into the neural dynamics producing vestibulocollic reflexes, which may respond to high-frequency transient events to stabilize the head.

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 < 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.

Soleus responses to Achilles tendon stimuli are suppressed by heel and enhanced by metatarsal cutaneous stimuli during standing.

KEY POINTS: We examined the influence of cutaneous feedback from the heel and metatarsal regions of the foot sole on the soleus stretch reflex pathway during standing. We found that heel electrical stimuli suppressed and metatarsal stimuli enhanced the soleus vibration response. Follow-up experiments indicated that the interaction between foot sole cutaneous feedback and the soleus vibration response was likely not mediated by presynaptic inhibition and was contingent upon a modulation at the ⍺-motoneuron pool level. The spatially organized interaction between cutaneous feedback from the foot sole and the soleus vibration response provides information about how somatosensory information is combined to appropriately respond to perturbations during standing. ABSTRACT: Cutaneous feedback from the foot sole provides balance-relevant information and has the potential to interact with spinal reflex pathways. In this study, we examined how cutaneous feedback from the foot sole (heel and metatarsals) influenced the soleus response to proprioceptive stimuli during standing. We delivered noisy vibration (10-115 Hz) to the right Achilles tendon while we intermittently applied electrical pulse trains (five 1-ms pulses at 200 Hz, every 0.8-1.0 s) to the skin under either the heel or the metatarsals of the ipsilateral foot sole. We analysed time-dependent (referenced to cutaneous stimuli) coherence and cross-correlations between the vibration acceleration and rectified soleus EMG. Vibration-EMG coherence was observed across a bandwidth of ∼10-80 Hz, and coherence was suppressed by heel but enhanced by metatarsal cutaneous stimuli. Cross-correlations showed soleus EMG was correlated with the vibration (∼40 ms lag) and cross-correlations were also suppressed by heel (from 104-155 ms) but enhanced by metatarsal (from 76-128 ms) stimuli. To examine the neural mechanisms mediating this reflex interaction, we conducted two further experiments to probe potential contributions from (1) presynaptic inhibition, and (2) modulations at the ⍺- and γ-motoneuron pools. Results suggest the cutaneous interactions with the stretch reflex pathway required a modulation at the ⍺-motoneuron pool and were likely not mediated by presynaptic inhibition. These findings demonstrate that foot sole cutaneous information functionally tunes the stretch reflex pathway during the control of upright posture and balance.

Regional activation in the human longissimus thoracis pars lumborum muscle.

KEY POINTS: •Longissimus activity in the lumbar region was measured using indwelling electromyography to characterize the territory of its motor units. •The distribution of motor units in the longissimus pars lumborum muscle was mainly grouped into two distinct regions. •Regional activation of the longissimus pars lumborum was also observed during functional tasks involving trunk movements. •The regional activation of the longissimus pars lumborum muscle may play a role in segmental stabilization of the lumbar spine. ABSTRACT: The longissimus pars lumborum contributes to lumbar postural control and movement. While animal studies suggest a segmental control of this muscle, the territory of motor units constituting the human longissimus pars lumborum remains unknown. The aims of this study were to identify the localization of motor unit territories in the longissimus and assess the activation of this muscle during functional tasks. Eight healthy participants were recruited. During isometric back extension contractions, single motor-unit (at L1, L2, L3 and L4) and multi-unit indwelling recordings (at L1, L1-L2, L2, L2-L3, L3, L3-L4 and L4) were used to estimate motor unit territories in the longissimus pars lumborum based on the motor-unit spike-triggered averages from fine-wire electrodes. A series of functional tasks involving trunk and arm movements were also performed. A total of 73 distinct motor units were identified along the length of the longissimus: only two motor units spanned all recording sites. The majority of the recorded motor units had muscle fibres located in two main rostro-caudal territories (32 motor units spanned L1 to L3 and 30 spanned ∼L3 to L4) and 11 had muscle fibres outside these two main territories. We also observed distinct muscle activation between the rostral and caudal regions of the longissimus pars lumborum during a trunk rotation task. Our results show clear rostral and caudal motor unit territories in the longissimus pars lumborum muscle and suggest that the central nervous system can selectively activate regions of the superficial lumbar muscles to provide local stabilization of the spine.

Influence of age on the frequency characteristics of the soleus muscle response to Achilles tendon vibration during standing.

KEY POINTS: Proprioceptive sensory information from the ankle joint is critical for the control of upright posture and balance. We examined the influence of age (n = 54 healthy adults, 20-82 years old) on lower limb muscle responses to proprioceptive perturbations evoked by Achilles tendon vibration during standing. The frequency bandwidth of the muscle response became narrower, and the gain (the muscle response relative to the stimulus) and scaling (increases in response amplitude with increases in stimulus amplitude) decreased with age. Mechanics of the muscle-tendon unit (mechanical admittance) did not differ with age during standing, and thus probably did not mediate the age-related changes observed in soleus muscle responses to vibration. These findings add to our understanding of how altered proprioceptive responses may contribute to impaired mobility and falls with ageing. ABSTRACT: Proprioceptive information from the ankle joint plays an important role in the control of upright posture and balance. Ageing influences many components of the sensorimotor system, which leads to poor mobility and falls. However, little is known about the influence of age on the characteristics of short latency muscle responses to proprioceptive stimuli during standing across frequencies that are encoded by muscle spindles. We examined the frequency characteristics of the soleus muscle response to noisy (10-115 Hz) Achilles tendon vibration during standing in 54 healthy adults across a broad age range (20-82 years). The results showed the frequency bandwidth of the soleus response (vibration-electromyography coherence) became progressively narrower with ageing. Coherence was significantly lower in middle-aged relative to young adults between ∼7-11 and 28-62 Hz, lower in older relative to middle-aged adults between ∼30-50 Hz and lower in older relative to young adults between ∼7-64 Hz. Muscle response gain was similar between age groups at low frequencies, although gain was lower in older relative to young adults between ∼28-54 Hz. Across the age range, the response amplitude (peak-to-peak cross-covariance) and the scaling of the response with stimulus amplitude were both negatively correlated with age. Muscle-tendon mechanics (admittance) did not differ with age, suggesting this did not mediate differences in soleus responses. Our findings suggest there is a progressive change in the soleus response to proprioceptive stimuli with ageing during standing, which could contribute to poorer mobility and falls.

Virtual signals of head rotation induce gravity-dependent inferences of linear acceleration.

KEY POINTS: Considerable debate exists regarding whether electrical vestibular stimuli encoded by vestibular afferents induce a net signal of linear acceleration, rotation or a combination of the two. This debate exists because an isolated signal of head rotation encoded by the vestibular afferents can cause perceptions of both linear and angular motion. We recorded participants' perceptions in different orientations relative to gravity and predicted their responses by modelling the effect of electrical vestibular stimuli on vestibular afferents and a current model of central vestibular processing. We show that, even if electrical vestibular stimuli are encoded as a net signal of head rotation, participants perceive both linear acceleration and rotation motions, provided the electrical stimulation-induced rotational vector has a component orthogonal to gravity. The emergence of a perception of linear acceleration from a single rotational input signal clarifies the origins of the neural mechanisms underlying electrical vestibular stimulation. ABSTRACT: Electrical vestibular stimulation (EVS) is an increasingly popular biomedical tool for generating sensations of virtual motion in humans, for which the mechanism of action is a topic of considerable debate. Contention surrounds whether the evoked vestibular afferent activity encodes a signal of net rotation and/or linear acceleration. Central processing of vestibular self-motion signals occurs through an internal representation of gravity that can lead to inferred linear accelerations in absence of a true inertial acceleration. Applying this model to virtual signals of rotation evoked by EVS, we predict that EVS will induce behaviours attributed to both angular and linear motion, depending on the head orientation relative to gravity. To demonstrate this, 18 subjects indicated their perceived motion during sinusoidal EVS when in one of four head/body positions orienting the gravitational vector parallel or orthogonal to the EVS rotation vector. During stimulation, participants selected one simulated movement from seven that corresponded best to what they perceived. Participants' responses in each orientation were predicted by a model combining the influence of EVS on vestibular afferents with known mechanisms of vestibular processing. When the EVS rotation vector had a component orthogonal to gravity, human perceptual responses were consistent with a non-zero central estimate of interaural or superior-inferior linear acceleration. The emergence of a perception of linear acceleration from a single rotational input signal clarifies the origins of the neural mechanisms underlying EVS, which has important implications for its use in human biomedical or sensory augmentation applications.

Soleus single motor units show stronger coherence with Achilles tendon vibration across a broad bandwidth relative to medial gastrocnemius units while standing.

To probe the frequency characteristics of somatosensory responses in the triceps surae muscles, we previously applied suprathreshold noisy vibration to the Achilles tendon and correlated it with ongoing triceps surae muscle activity (recorded via surface EMG) during standing. Stronger responses to tendon stimuli were observed in soleus (Sol) relative to medial gastrocnemius (MGas) surface EMG; however, it is unknown whether differences in motor unit activity or limitations of surface EMG could have influenced this finding. Here, we inserted indwelling EMG into Sol and MGas to record the activity of single motor units while we applied noisy vibration (10-115 Hz) to the right Achilles tendon of standing participants. We analyzed the relationship between vibration acceleration and the spike activity of active single motor units through estimates of coherence, gain, phase, and cross-covariance. We also applied sinusoidal vibration at frequencies from 10 to 100 Hz (in 5-Hz increments) to examine whether motor units demonstrate nonlinear synchronization or phase locking at higher frequencies. Relative to MGas single motor units, Sol units demonstrated stronger coherence and higher gain with noisy vibration across a bandwidth of 7-68 Hz, and larger peak-to-peak cross-covariance at all four stimulus amplitudes examined. Sol and MGas motor unit activity was modulated over the time course of the sinusoidal stimuli across all frequencies, but their phase-locking behavior was minimal. These findings suggest Sol plays a prominent role in responding to disturbances transmitted through the Achilles tendon across a broad frequency band during standing.NEW & NOTEWORTHY We examined the relationship between Achilles tendon stimuli and spike times of single soleus (Sol) and medial gastrocnemius (MGas) motor units during standing. Relative to MGas, Sol units demonstrated stronger coherence and higher gain with noisy stimuli across a bandwidth of 7-68 Hz. Sol and MGas units demonstrated minimal nonlinear phase locking with sinusoidal stimuli. These findings indicate Sol plays a prominent role in responding to tendon stimuli across a broad frequency band.

Increased human stretch reflex dynamic sensitivity with height-induced postural threat.

KEY POINTS: Threats to standing balance (postural threat) are known to facilitate soleus tendon-tap reflexes, yet the mechanisms driving reflex changes are unknown. Scaling of ramp-and-hold dorsiflexion stretch reflexes to stretch velocity and amplitude were examined as indirect measures of changes to muscle spindle dynamic and static function with height-induced postural threat. Overall, stretch reflexes were larger with threat. Furthermore, the slope (gain) of the stretch-velocity vs. short-latency reflex amplitude relationship was increased with threat. These findings are interpreted as indirect evidence for increased muscle spindle dynamic sensitivity, independent of changes in background muscle activity levels, with a threat to standing balance. We argue that context-dependent scaling of stretch reflexes forms part of a multisensory tuning process where acquisition and/or processing of balance-relevant sensory information is continuously primed to facilitate feedback control of standing balance in challenging balance scenarios. ABSTRACT: Postural threat increases soleus tendon-tap (t-) reflexes. However, it is not known whether t-reflex changes are a result of central modulation, altered muscle spindle dynamic sensitivity or combined spindle static and dynamic sensitization. Ramp-and-hold dorsiflexion stretches of varying velocities and amplitudes were used to examine velocity- and amplitude-dependent scaling of short- (SLR) and medium-latency (MLR) stretch reflexes as an indirect indicator of spindle sensitivity. t-reflexes were also performed to replicate previous work. In the present study, we examined the effects of postural threat on SLR, MLR and t-reflex amplitude, as well as SLR-stretch velocity scaling. Forty young-healthy adults stood with one foot on a servo-controlled tilting platform and the other on a stable surface. The platform was positioned on a hydraulic lift. Threat was manipulated by having participants stand in low (height 1.1 m; away from edge) then high (height 3.5 m; at the edge) threat conditions. Soleus stretch reflexes were recorded with surface electromyography and SLRs and MLRs were probed with fixed-amplitude variable-velocity stretches. t-reflexes were evoked with Achilles tendon taps using a linear motor. SLR, MLR and t-reflexes were 11%, 9.5% and 16.9% larger, respectively, in the high compared to low threat condition. In 22 out of 40 participants, SLR amplitude was correlated to stretch velocity at both threat levels. In these participants, the gain of the SLR-velocity relationship was increased by 36.1% with high postural threat. These findings provide new supportive evidence for increased muscle spindle dynamic sensitivity with postural threat and provide further support for the context-dependent modulation of human somatosensory pathways.

Neck muscle biomechanics and neural control.

The mechanics, morphometry, and geometry of our joints, segments, and muscles are fundamental biomechanical properties intrinsic to human neural control. The goal of our study was to investigate whether the biomechanical actions of individual neck muscles predict their neural control. Specifically, we compared the moment direction and variability produced by electrical stimulation of a neck muscle (biomechanics) to the preferred activation direction and variability (neural control). Subjects sat upright with their head fixed to a six-axis load cell and their torso restrained. Indwelling wire electrodes were placed into the sternocleidomastoid (SCM), splenius capitis (SPL), and semispinalis capitis (SSC) muscles. The electrically stimulated direction was defined as the moment direction produced when a current (2-19 mA) was passed through each muscle's electrodes. Preferred activation direction was defined as the vector sum of the spatial tuning curve built from root mean squared electromyogram when subjects produced isometric moments at 7.5% and 15% of their maximum voluntary contraction (MVC) in 26 three-dimensional directions. The spatial tuning curves at 15% MVC were well defined (unimodal, P < 0.05), and their preferred directions were 23°, 39°, and 21° different from their electrically stimulated directions for the SCM, SPL, and SSC, respectively ( P < 0.05). Intrasubject variability was smaller in electrically stimulated moment directions compared with voluntary preferred directions, and intrasubject variability decreased with increased activation levels. Our findings show that the neural control of neck muscles is not based solely on optimizing individual muscle biomechanics but, as activation increases, biomechanical constraints in part dictate the activation of synergistic neck muscles. NEW & NOTEWORTHY Biomechanics are an intrinsic part of human neural control. In this study, we found that the biomechanics of individual neck muscles cannot fully predict their neural control. Consequently, physiologically based computational neck muscle controllers cannot calculate muscle activation schemes based on the isolated biomechanics of muscles. Furthermore, by measuring biomechanics we showed that the intrasubject variability of the neural control was lower for electrical vs. voluntary activation of the neck muscles.

Transformation of Vestibular Signals for the Control of Standing in Humans.

During standing balance, vestibular signals encode head movement and are transformed into coordinates that are relevant to maintaining upright posture of the whole body. This transformation must account for head-on-body orientation as well as the muscle actions generating the postural response. Here, we investigate whether this transformation is dependent upon a muscle's ability to stabilize the body along the direction of a vestibular disturbance. Subjects were braced on top of a robotic balance system that simulated the mechanics of standing while being exposed to an electrical vestibular stimulus that evoked a craniocentric vestibular error of head roll. The balance system was limited to move in a single plane while the vestibular error direction was manipulated by having subjects rotate their head in yaw. Vestibular-evoked muscle responses were greatest when the vestibular error was aligned with the balance direction and decreased to zero as the two directions became orthogonal. This demonstrates that muscles respond only to the component of the error that is aligned with the balance direction and thus relevant to the balance task, not to the cumulative afferent activity, as expected for vestibulospinal reflex loops. When we reversed the relationship between balancing motor commands and associated vestibular sensory feedback, the direction of vestibular-evoked ankle compensatory responses was also reversed. This implies that the nervous system quickly reassociates new relationships between vestibular sensory signals and motor commands related to maintaining balance. These results indicate that vestibular-evoked muscle activity is a highly flexible balance response organized to compensate for vestibular disturbances. SIGNIFICANCE STATEMENT: The postural corrections critical to standing balance and navigation rely on transformation of sensory information into reference frames that are relevant for the required motor actions. Here, we demonstrate that the nervous system transforms vestibular sensory signals of head motion according to a muscle's ability to stabilize the body along the direction of a vestibular-evoked disturbance. By manipulating the direction of the imposed vestibular signal relative to a muscle's action, we show that the vestibular contribution to muscle activity is a highly flexible and organized balance response. This study provides insight into the neural integration and central processing associated with transformed vestibulomotor relationships that are essential to standing upright.

Regionalization of the stretch reflex in the human vastus medialis.

KEY POINTS: Regionalization of the stretch reflex, i.e. the notion that the activation of 1a afferents from a muscle region influences only the activation of motor units in the same region, has been demonstrated previously in animals but not in humans. Mechanical stretches applied to regions of vastus medialis as close as 10 mm apart resulted in recruitment of motor units localized topographically with respect to the location of the mechanical stretch. Stretch reflexes are regionalized in the human vastus medialis. The human spinal cord has the neuromuscular circuitry to preferentially activate motoneurones innervating muscle fibres located in different regions of the vastus medialis. ABSTRACT: The localization of motor unit territories provides an anatomical basis to suggest that the CNS may have more independence in motor unit recruitment and control strategies than what was previously thought. In this study, we investigated whether the human spinal cord has the neuromuscular circuitry to independently activate motor units located in different regions of the vastus medialis. Mechanical taps were applied to multiple locations in the vastus medialis (VM) in nine healthy individuals. Regional responses within the muscle were observed using a grid of 5 × 13 surface EMG electrodes. The EMG amplitude was quantified for each channel, and a cluster of channels showing the largest activation was identified. The spatial location of the EMG response was quantified as the position of the channels in the cluster. In a subset of three participants, intramuscular recordings were performed simultaneously with the surface EMG recordings. Mechanical taps resulted in localized, discrete responses for each participant. The spatial location of the elicited responses was dependent on the location of the tap (P < 0.001). Recordings with intramuscular electrodes confirmed the regional activation of the VM for different tap locations. Selective stimulation of 1a afferents localized in a region of the VM results in reflex recruitment of motor units in the same region. These findings suggest that the human spinal cord has the neuromuscular circuitry to modulate spatially the motoneuronal output to vastus medialis regions, which is a neuroanatomical prerequisite for regional activation.

The internal representation of head orientation differs for conscious perception and balance control.

KEY POINTS: We tested perceived head-on-feet orientation and the direction of vestibular-evoked balance responses in passively and actively held head-turned postures. The direction of vestibular-evoked balance responses was not aligned with perceived head-on-feet orientation while maintaining prolonged passively held head-turned postures. Furthermore, static visual cues of head-on-feet orientation did not update the estimate of head posture for the balance controller. A prolonged actively held head-turned posture did not elicit a rotation in the direction of the vestibular-evoked balance response despite a significant rotation in perceived angular head posture. It is proposed that conscious perception of head posture and the transformation of vestibular signals for standing balance relying on this head posture are not dependent on the same internal representation. Rather, the balance system may operate under its own sensorimotor principles, which are partly independent from perception. ABSTRACT: Vestibular signals used for balance control must be integrated with other sensorimotor cues to allow transformation of descending signals according to an internal representation of body configuration. We explored two alternative models of sensorimotor integration that propose (1) a single internal representation of head-on-feet orientation is responsible for perceived postural orientation and standing balance or (2) conscious perception and balance control are driven by separate internal representations. During three experiments, participants stood quietly while passively or actively maintaining a prolonged head-turned posture (>10 min). Throughout the trials, participants intermittently reported their perceived head angular position, and subsequently electrical vestibular stimuli were delivered to elicit whole-body balance responses. Visual recalibration of head-on-feet posture was used to determine whether static visual cues are used to update the internal representation of body configuration for perceived orientation and standing balance. All three experiments involved situations in which the vestibular-evoked balance response was not orthogonal to perceived head-on-feet orientation, regardless of the visual information provided. For prolonged head-turned postures, balance responses consistent with actual head-on-feet posture occurred only during the active condition. Our results indicate that conscious perception of head-on-feet posture and vestibular control of balance do not rely on the same internal representation, but instead treat sensorimotor cues in parallel and may arrive at different conclusions regarding head-on-feet posture. The balance system appears to bypass static visual cues of postural orientation and mainly use other sensorimotor signals of head-on-feet position to transform vestibular signals of head motion, a mechanism appropriate for most daily activities.

Both standing and postural threat decrease Achilles' tendon reflex inhibition from tendon electrical stimulation.

KEY POINTS: Golgi tendon organs (GTOs) and associated Ib reflexes contribute to standing balance, but the potential impacts of threats to standing balance on Ib reflexes are unknown. Tendon electrical stimulation to the Achilles' tendon was used to probe changes in Ib inhibition in medial gastrocnemius with postural orientation (lying prone vs. upright standing; experiment 1) and height-induced postural threat (standing at low and high surface heights; experiment 2). Ib inhibition was reduced while participants stood upright, compared to lying prone (42.2%); and further reduced when standing in the high, compared to low, threat condition (32.4%). These experiments will impact future research because they demonstrate that tendon electrical stimulation can be used to probe Ib reflexes in muscles engaged in standing balance. These results provide novel evidence that human short-latency GTO-Ib reflexes are dependent upon both task, as evidenced by changes with postural orientation, and context, such as height-induced postural threat during standing. ABSTRACT: Golgi tendon organ Ib reflexes are thought to contribute to standing balance control, but it is unknown if they are modulated when people are exposed to a postural threat. We used a novel application of tendon electrical stimulation (TStim) to elicit Ib inhibitory reflexes in the medial gastrocnemius, while actively engaged in upright standing balance, to examine (a) how Ib reflexes to TStim are influenced by upright stance, and (b) the effects of height-induced postural threat on Ib reflexes during standing. TStim evoked short-latency (<47 ms) inhibition apparent in trigger-averaged rectified EMG, which was quantified in terms of area, duration and mean amplitude of inhibition. In order to validate the use of TStim in a standing model, TStim-Ib inhibition was compared from conditions where participants were lying prone vs. standing upright. TStim evoked Ib inhibition in both conditions; however, significant reductions in Ib inhibition area (42.2%) and duration (32.9%) were observed during stance. Postural threat, manipulated by having participants stand at LOW (0.8 m high, 0.6 m from edge) and HIGH (3.2 m, at edge) elevated surfaces, significantly reduced Ib inhibition area (32.4%), duration (16.4%) and amplitude (24.8%) in the HIGH, compared to LOW, threat condition. These results demonstrate TStim is a viable technique for investigating Ib reflexes in standing, and confirm Ib reflexes are modulated with postural orientation. The novel observation of reduced Ib inhibition with elevated postural threat reveals that human Ib reflexes are context dependent, and the human Ib reflex pathways are modulated by threat or emotional processing centres of the CNS.

Rapid limb-specific modulation of vestibular contributions to ankle muscle activity during locomotion.

KEY POINTS: The vestibular influence on human walking is phase-dependent and modulated across both limbs with changes in locomotor velocity and cadence. Using a split-belt treadmill, we show that vestibular influence on locomotor activity is modulated independently in each limb. The independent vestibular modulation of muscle activity from each limb occurs rapidly at the onset of split-belt walking, over a shorter time course relative to the characteristic split-belt error-correction mechanisms (i.e. muscle activity and kinematics) associated with locomotor adaptation. Together, the present results indicate that the nervous system rapidly modulates the vestibular influence of each limb separately through processes involving ongoing sensory feedback loops. These findings help us understand how vestibular information is used to accommodate the variable and commonplace demands of locomotion, such as turning or navigating irregular terrain. ABSTRACT: During walking, the vestibular influence on locomotor activity is phase-dependent and modulated in both limbs with changes in velocity. It is unclear, however, whether this bilateral modulation is due to a coordinated mechanism between both limbs or instead through limb-specific processes that remain masked by the symmetric nature of locomotion. Here, human subjects walked on a split-belt treadmill with one belt moving at 0.4 m s-1 and the other moving at 0.8 m s-1 while exposed to an electrical vestibular stimulus. Muscle activity was recorded bilaterally around the ankles of each limb and used to compare vestibulo-muscular coupling between velocity-matched and unmatched tied-belt walking. In general, response magnitudes decreased by ∼20-50% and occurred ∼13-20% earlier in the stride cycle at the higher belt velocity. This velocity-dependent modulation of vestibular-evoked muscle activity was retained during split-belt walking and was similar, within each limb, to velocity-matched tied-belt walking. These results demonstrate that the vestibular influence on ankle muscles during locomotion can be adapted independently to each limb. Furthermore, modulation of vestibular-evoked muscle responses occurred rapidly (∼13-34 strides) after onset of split-belt walking. This rapid adaptation contrasted with the prolonged adaptation in step length symmetry (∼128 strides) as well as EMG magnitude and timing (∼40-100 and ∼20-70 strides, respectively). These results suggest that vestibular influence on ankle muscle control is adjusted rapidly in sensorimotor control loops as opposed to longer-term error correction mechanisms commonly associated with split-belt adaptation. Rapid limb-specific sensorimotor feedback adaptation may be advantageous for asymmetric overground locomotion, such as navigating irregular terrain or turning.

Exercise-induced quadriceps muscle fatigue in men and women: effects of arterial oxygen content and respiratory muscle work.

KEY POINTS: High work of breathing and exercise-induced arterial hypoxaemia (EIAH) can decrease O2 delivery and exacerbate exercise-induced quadriceps fatigue in healthy men. Women have a higher work of breathing during exercise, dedicate a greater fraction of whole-body V̇O2 towards their respiratory muscles and develop EIAH. Despite a greater reduction in men's work of breathing, the attenuation of quadriceps fatigue was similar between the sexes. The degree of EIAH was similar between sexes, and regardless of sex, those who developed the greatest hypoxaemia during exercise demonstrated the most attenuation of quadriceps fatigue. Based on our previous finding that women have a greater relative oxygen cost of breathing, women appear to be especially susceptible to work of breathing-related changes in quadriceps muscle fatigue. ABSTRACT: Reducing the work of breathing or eliminating exercise-induced arterial hypoxaemia (EIAH) during exercise decreases the severity of quadriceps fatigue in men. Women have a greater work of breathing during exercise, dedicate a greater fraction of whole-body V̇O2 towards their respiratory muscles, and demonstrate EIAH, suggesting women may be especially susceptible to quadriceps fatigue. Healthy subjects (8 male, 8 female) completed three constant load exercise tests over 4 days. During the first (control) test, subjects exercised at ∼85% of maximum while arterial blood gases and work of breathing were assessed. Subsequent constant load exercise tests were iso-time and iso-work rate, but with EIAH prevented by inspiring hyperoxic gas or work of breathing reduced via a proportional assist ventilator (PAV). Quadriceps fatigue was assessed by measuring force in response to femoral nerve stimulation. For both sexes, quadriceps force was equally reduced after the control trial (-27 ± 2% baseline) and was attenuated with hyperoxia and PAV (-18 ± 1 and -17 ± 2% baseline, P < 0.01, respectively), with no sex difference. EIAH was similar between the sexes, and regardless of sex, subjects with the lowest oxyhaemoglobin saturation during the control test had the greatest quadriceps fatigue attenuation with hyperoxia (r2  = 0.79, P < 0.0001). For the PAV trial, despite reducing the work of breathing to a greater degree in men (men: 60 ± 5, women: 75 ± 6% control, P < 0.05), the attenuation of quadriceps fatigue was similar between the sexes (36 ± 4 vs. 37 ± 7%). Owing to a greater relative V̇O2 of the respiratory muscles in women, less of a change in work of breathing is needed to reduce quadriceps fatigue.

Postural threat influences vestibular-evoked muscular responses.

Standing balance is significantly influenced by postural threat. While this effect has been well established, the underlying mechanisms of the effect are less understood. The involvement of the vestibular system is under current debate, and recent studies that investigated the effects of height-induced postural threat on vestibular-evoked responses provide conflicting results based on kinetic (Horslen BC, Dakin CJ, Inglis JT, Blouin JS, Carpenter MG. J Physiol 592: 3671-3685, 2014) and kinematic (Osler CJ, Tersteeg MC, Reynolds RF, Loram ID. Eur J Neurosci 38: 3239-3247, 2013) data. We examined the effect of threat of perturbation, a different form of postural threat, on coupling (cross-correlation, coherence, and gain) of the vestibulo-muscular relationship in 25 participants who maintained standing balance. In the "No-Threat" conditions, participants stood quietly on a stable surface. In the "Threat" condition, participants' balance was threatened with unpredictable mediolateral support surface tilts. Quiet standing immediately before the surface tilts was compared to an equivalent time from the No-Threat conditions. Surface EMG was recorded from bilateral trunk, hip, and leg muscles. Hip and leg muscles exhibited significant increases in peak cross-correlation amplitudes, coherence, and gain (1.23-2.66×) in the Threat condition compared with No-Threat conditions, and significant correlations were observed between threat-related changes in physiological arousal and medium-latency peak cross-correlation amplitude in medial gastrocnemius (r = 0.408) muscles. These findings show a clear threat effect on vestibular-evoked responses in muscles in the lower body, with less robust effects of threat on trunk muscles. Combined with previous work, the present results can provide insight into observed changes during balance control in threatening situations. NEW & NOTEWORTHY: This is the first study to show increases in vestibular-evoked responses of the lower body muscles under conditions of increased threat of postural perturbation. While robust findings were observed in hip and leg muscles, less consistent results were found in muscles of the trunk. The present findings provide further support in the ongoing debate for arguments that vestibular-evoked balance responses are influenced by fear and anxiety and explain previous threat-related changes in balance.

Vestibular contribution to balance control in the medial gastrocnemius and soleus.

The soleus (Sol) and medial gastrocnemius (mGas) muscles have different patterns of activity during standing balance and may have distinct functional roles. Using surface electromyography we previously observed larger responses to galvanic vestibular stimulation (GVS) in the mGas compared with the Sol muscle. However, it is unclear whether this difference is an artifact that reflects limitations associated with surface electromyography recordings or whether a compensatory balance response to a vestibular error signal activates the mGas to a greater extent than the Sol. In the present study, we compared the effect of GVS on the discharge behavior of 9 Sol and 21 mGas motor units from freely standing subjects. In both Sol and mGas motor units, vestibular stimulation induced biphasic responses in measures of discharge timing [11 ± 5.0 (mGas) and 5.6 ± 3.8 (Sol) counts relative to the sham (mean ± SD)], and frequency [0.86 ± 0.6 Hz (mGas), 0.34 ± 0.2 Hz (Sol) change relative to the sham]. Peak-to-trough response amplitudes were significantly larger in the mGas (62% in the probability-based measure and 160% in the frequency-based measure) compared with the Sol (multiple P < 0.05). Our results provide direct evidence that vestibular signals have a larger influence on the discharge activity of motor units in the mGas compared with the Sol. More tentatively, these results indicate the mGas plays a greater role in vestibular-driven balance corrections during standing balance.

Motor units in the human medial gastrocnemius muscle are not spatially localized or functionally grouped.

KEY POINTS: Human medial gastrocnemius (MG) motor units (MUs) are thought to occupy small muscle territories or regions, with low-threshold units preferentially located distally. We used intramuscular recordings to measure the territory of muscle fibres from MG MUs and determine whether these MUs are grouped by recruitment threshold or joint action (ankle plantar flexion and knee flexion). The territory of MUs from the MG muscle varied from somewhat localized to highly distributed, with approximately half the MUs spanning at least half the length and width of the muscle. There was also no evidence of regional muscle activity based on MU recruitment thresholds or joint action. The CNS does not have the means to selectively activate regions of the MG muscle based on task requirements. ABSTRACT: Human medial gastrocnemius (MG) motor units (MUs) are thought to occupy small muscle territories, with low-threshold units preferentially located distally. In this study, subjects (n = 8) performed ramped and sustained isometric contractions (ankle plantar flexion and knee flexion; range: ∼1-40% maximal voluntary contraction) and we measured MU territory size with spike-triggered averages from fine-wire electrodes inserted along the length (seven electrodes) or across the width (five electrodes) of the MG muscle. Of 69 MUs identified along the length of the muscle, 32 spanned at least half the muscle length (≥ 6.9 cm), 11 of which spanned all recording sites (13.6-17.9 cm). Distal fibres had smaller pennation angles (P < 0.05), which were accompanied by larger territories in MUs with fibres located distally (P < 0.05). There was no distal-to-proximal pattern of muscle activation in ramp contraction (P = 0.93). Of 36 MUs identified across the width of the muscle, 24 spanned at least half the muscle width (≥ 4.0 cm), 13 of which spanned all recording sites (8.0-10.8 cm). MUs were not localized (length or width) based on recruitment threshold or contraction type, nor was there a relationship between MU territory size and recruitment threshold (Spearman's rho = -0.20 and 0.13, P > 0.18). MUs in the human MG have larger territories than previously reported and are not localized based on recruitment threshold or joint action. This indicates that the CNS does not have the means to selectively activate regions of the MG muscle based on task requirements.