Reduced inhibition from quadriceps onto soleus after acute quadriceps fatigue suggests Golgi tendon organ contribution to heteronymous inhibition.

Heteronymous inhibition between lower limb muscles is primarily attributed to recurrent inhibitory circuits in humans but could also arise from Golgi tendon organs (GTOs). Distinguishing between recurrent inhibition and mechanical activation of GTOs is challenging because their heteronymous effects are both elicited by stimulation of nerves or a muscle above motor threshold. Here, the unique influence of mechanically activated GTOs was examined by comparing the magnitude of heteronymous inhibition from quadriceps (Q) muscle stimulation onto ongoing soleus electromyographic at five Q stimulation intensities (1.5-2.5× motor threshold) before and after an acute bout of stimulation-induced Q fatigue. Fatigue was used to decrease Q stimulation evoked force (i.e., decreased GTO activation) despite using the same pre-fatigue stimulation currents (i.e., same antidromic recurrent inhibition input). Thus, a decrease in heteronymous inhibition after Q fatigue and a linear relation between stimulation-evoked torque and inhibition both before and after fatigue would support mechanical activation of GTOs as a source of inhibition. A reduction in evoked torque but no change in inhibition would support recurrent inhibition. After fatigue, Q stimulation-evoked knee torque, heteronymous inhibition magnitude and inhibition duration were significantly decreased for all stimulation intensities. In addition, heteronymous inhibition magnitude was linearly related to twitch-evoked knee torque before and after fatigue. These findings support mechanical activation of GTOs as a source of heteronymous inhibition along with recurrent inhibition. The unique patterns of heteronymous inhibition before and after fatigue across participants suggest the relative contribution of GTOs, and recurrent inhibition may vary across persons.

Quadriceps muscle stimulation evokes heteronymous inhibition onto soleus with limited Ia activation compared to femoral nerve stimulation.

Heteronymous excitatory feedback from muscle spindles and inhibitory feedback from Golgi tendon organs and recurrent inhibitory circuits can influence motor coordination. The functional role of inhibitory feedback is difficult to determine, because nerve stimulation, the primary method used in humans, cannot evoke inhibition without first activating the largest diameter muscle spindle axons. Here, we tested the hypothesis that quadriceps muscle stimulation could be used to examine heteronymous inhibition more selectively when compared to femoral nerve stimulation by comparing the effects of nerve and muscle stimulation onto ongoing soleus EMG held at 20% of maximal effort. Motor threshold and two higher femoral nerve and quadriceps stimulus intensities matched by twitch evoked torque magnitudes were examined. We found that significantly fewer participants exhibited excitation during quadriceps muscle stimulation when compared to nerve stimulation (14-29% vs. 64-71% of participants across stimulation intensities) and the magnitude of heteronymous excitation from muscle stimulation, when present, was much reduced compared to nerve stimulation. Muscle and nerve stimulation resulted in heteronymous inhibition that significantly increased with increasing stimulation evoked torque magnitudes. This study provides novel evidence that muscle stimulation may be used to more selectively examine inhibitory heteronymous feedback between muscles in the human lower limb when compared to nerve stimulation.

Perturbation-induced fast drifts in finger enslaving.

We explored changes in finger forces and in an index of unintentional finger force production (enslaving) under a variety of visual feedback conditions and positional finger perturbations. In particular, we tested a hypothesis that enslaving would show a consistent increase with time at characteristic times of about 1-2 s. Young healthy subjects performed accurate force production tasks under visual feedback on the total force of the instructed fingers (index and ring) or enslaved fingers (middle and little). Finger feedback was covertly alternated between master and enslaved fingers in a random fashion. The feedback could be presented over the first 5 s of the trial only or over the whole trial duration (21 s). After 5 s, the fingers were lifted by 1 cm, and after 15 s, the fingers were lowered to the initial position. The force of the instructed fingers drifted toward lower magnitudes in all conditions except the one with continuous feedback on that force. The force of enslaved fingers showed variable behavior across conditions. In all conditions, the index of enslaving showed a consistent increase with the time constant varying between 1 and 3 s. We interpret the results as pointing at the spread of excitation to enslaved fingers (possibly, in the cortical M1 areas). The relatively fast changes in enslaving under positional finger perturbations suggest that quick changes of the input into M1 from pre-M1 areas can accelerate the hypothesized spread of cortical excitation.

What do people match when they try to match force? Analysis at the level of hypothetical control variables.

We used the theory of control with spatial referent coordinates (RC) to explore how young, healthy persons modify finger pressing force and match forces between the two hands. Three specific hypotheses were tested related to patterns of RC and apparent stiffness (defined as the slope of force-coordinate relation) used in the presence of visual feedback on the force and in its absence. The subjects used the right hand to produce accurate force under visual feedback; further the force could be increased or decreased, intentionally or unintentionally (induced by controlled lifting or lowering of the fingertips). The left hand was used to match force without visual feedback before and after the force change; the match hand consistently underestimated the actual force change in the task hand. The "inverse piano" device was used to compute RC and apparent stiffness. We found very high coefficients of determination for the inter-trial hyperbolic regressions between RC and apparent stiffness in the presence of visual feedback; the coefficients of determination dropped significantly without visual feedback. There were consistent preferred sharing patterns in the space of RC and apparent stiffness between the task and match hands across subjects. In contrast, there was much less consistency between the task and match hands in the magnitudes of RC and apparent stiffness observed in individual trials. Compared to the task hand, the match hand showed consistently lower magnitudes of apparent stiffness and, correspondingly, larger absolute magnitudes of RC. Involuntary force changes produced by lifting and lowering the force sensors led to significantly lower force changes compared to what could be expected based on the computed values of apparent stiffness and sensor movement amplitude. The results confirm the importance of visual feedback for stabilization of force in the space of hypothetical control variables. They suggest the existence of personal traits reflected in preferred ranges of RC and apparent stiffness across the two hands. They also show that subjects react to external perturbations, even when instructed "not to interfere": Such perturbations cause unintentional and unperceived drifts in both RC and apparent stiffness.

Case Studies in Neuroscience: The central and somatosensory contributions to finger interdependence and coordination: lessons from a study of a "deafferented person".

We tested finger force interdependence and multifinger force-stabilizing synergies in a patient with large-fiber peripheral neuropathy ("deafferented person"). The subject performed a range of tasks involving accurate force production with one finger and with four fingers. In one-finger tasks, nontask fingers showed unintentional force production (enslaving) with an atypical pattern: very large indices for the lateral (index and little) fingers and relatively small indices for the central (middle and ring) fingers. Indices of multifinger synergies stabilizing total force and of anticipatory synergy adjustments in preparation to quick force pulses were similar to those in age-matched control females. During constant force production, removing visual feedback led to a slow force drift to lower values (by ~25% over 15 s). The results support the idea of a neural origin of enslaving and suggest that the patterns observed in the deafferented person were reorganized based on everyday manipulation tasks. The lack of significant changes in the synergy index shows that synergic control can be organized in the absence of somatosensory feedback. We discuss the control of the hand in deafferented persons within the α-model of the equilibrium-point hypothesis and suggest that force drift results from an unintentional drift of the control variables to muscles toward zero values. NEW & NOTEWORTHY We demonstrate atypical patterns of finger enslaving and unchanged force-stabilizing synergies in a person with large-fiber peripheral neuropathy. The results speak strongly in favor of central origin of enslaving and its reorganization based on everyday manipulation tasks. The data show that synergic control can be implemented in the absence of somatosensory feedback. We discuss the control of the hand in deafferented persons within the α-model of the equilibrium-point hypothesis.

Force illusions and drifts observed during muscle vibration.

We explored predictions of a scheme that views position and force perception as a result of measuring proprioceptive signals within a reference frame set by ongoing efferent process. In particular, this hypothesis predicts force illusions caused by muscle vibration and mediated via changes in both afferent and efferent components of kinesthesia. Healthy subjects performed accurate steady force production tasks by pressing with the four fingers of one hand (the task hand) on individual force sensors with and without visual feedback. At various times during the trials, subjects matched the perceived force using the other hand. High-frequency vibration was applied to one or both of the forearms (over the hand and finger extensors). Without visual feedback, subjects showed a drop in the task hand force, which was significantly smaller under the vibration of that forearm. Force production by the matching hand was consistently higher than that of the task hand. Vibrating one of the forearms affected the matching hand in a manner consistent with the perception of higher magnitude of force produced by the vibrated hand. The findings were consistent between the dominant and nondominant hands. The effects of vibration on both force drift and force mismatching suggest that vibration led to shifts in both signals from proprioceptors and the efferent component of perception, the referent coordinate and/or coactivation command. The observations fit the hypothesis on combined perception of kinematic-kinetic variables with little specificity of different groups of peripheral receptors that all contribute to perception of forces and coordinates. NEW & NOTEWORTHY We show that vibration of hand/finger extensors produces consistent errors in finger force perception. Without visual feedback, finger force drifted to lower values without a drift in the matching force produced by the other hand; hand extensor vibration led to smaller finger force drift. The findings fit the scheme with combined perception of kinematic-kinetic variables and suggest that vibration leads to consistent shifts of the referent coordinate and, possibly, of coactivation command to the effector.

Multi-finger synergies and the muscular apparatus of the hand.

We explored whether the synergic control of the hand during multi-finger force production tasks depends on the hand muscles involved. Healthy subjects performed accurate force production tasks and targeted force pulses while pressing against loops positioned at the level of fingertips, middle phalanges, and proximal phalanges. This varied the involvement of the extrinsic and intrinsic finger flexors. The framework of the uncontrolled manifold (UCM) hypothesis was used to analyze the structure of inter-trial variance, motor equivalence, and anticipatory synergy adjustments prior to the force pulse in the spaces of finger forces and finger modes (hypothetical finger-specific control signals). Subjects showed larger maximal force magnitudes at the proximal site of force production. There were synergies stabilizing total force during steady-state phases across all three sites of force production; no differences were seen across the sites in indices of structure of variance, motor equivalence, or anticipatory synergy adjustments. Indices of variance, which did not affect the task (within the UCM), correlated with motor equivalent motion between the steady states prior to and after the force pulse; in contrast, variance affecting task performance did not correlate with non-motor equivalent motion. The observations are discussed within the framework of hierarchical control with referent coordinates for salient effectors at each level. The findings suggest that multi-finger synergies are defined at the level of abundant transformation between the low-dimensional hand level and higher dimensional finger level while being relatively immune to transformations between the finger level and muscle level. The results also support the scheme of control with two classes of neural variables that define referent coordinates and gains in back-coupling loops between hierarchical control levels.

Anticipatory synergy adjustments: preparing a quick action in an unknown direction.

We studied a mechanism of feed-forward control of a multi-finger action, namely anticipatory synergy adjustments (ASAs), prior to a quick force correction in response to a change in the gain of the visual feedback. Synergies were defined as co-varied across trials adjustments of commands to fingers that stabilized (decreased variance of) the total force. We hypothesized that ASAs would be highly sensitive to prior information about the timing of the action but not to information on its direction, i.e., on whether the gain would go up or down. The subjects produced accurate constant total force by pressing with four fingers on individual force sensors. The feedback signal could change from veridical (the sum of finger forces) to modified, with the middle finger force multiplied by 0.2 or by 1.8. The timing of the gain change and its direction could be known or unknown to the subject in advance. When the timing of the gain change was known, ASA was seen as a drop in the synergy index starting about 250-300 ms prior to the first visible correction of the total force. When the gain change timing was unknown, ASAs started much later, less than 100 ms prior to the total force correction. The magnitude of synergy index changes was significantly larger under the "time known" conditions. Information on the direction of the visual gain change had no effect on the ASA timing, while the ASA magnitude was somewhat larger when this information was not available to the subject. After the total force correction, the synergy index was significantly larger for the force signal computed using the modified gain values as compared to the synergy index value for the actual total force. We conclude that ASAs represent an important feed-forward motor control mechanism that allows preparing for a quick action even when the direction of the action is not known in advance. The results emphasize the subtle control of multi-finger synergies that are specific to the exact contributions of individual fingers to performance variables. The data fit well the central back-coupling hypothesis of synergies and the idea of control with referent body configurations.

Differential effect of heteronymous feedback from femoral nerve and quadriceps muscle stimulation onto soleus H-reflex.

Excitatory feedback from muscle spindles, and inhibitory feedback from Golgi tendon organs and recurrent inhibitory circuits are widely distributed within the spinal cord to modulate activity between human lower limb muscles. Heteronymous feedback is most commonly studied in humans by stimulating peripheral nerves, but the unique effect of non-spindle heteronymous feedback is difficult to determine due to the lower threshold of excitatory spindle axons. A few studies suggest stimulation of the muscle belly preferentially elicits non-spindle heteronymous feedback. However, there remains a lack of consensus on the differential effect of nerve and muscle stimulation onto the H-reflex, and the relation of the heteronymous effects onto H-reflex compared to that onto ongoing EMG has not been determined. In this cross-sectional study, we compared excitatory and inhibitory effects from femoral nerve and quadriceps muscle belly stimulation onto soleus H-reflex size in 15 able-bodied participants and in a subset also compared heteronymous effects onto ongoing soleus EMG at 10% and 20% max. Femoral nerve stimulation elicited greater excitation of the H-reflex compared to quadriceps stimulation. The differential effect was also observed onto ongoing soleus EMG at 20% max but not 10%. Femoral nerve and quadriceps stimulation elicited similar inhibition of the soleus H-reflexes, and these results were better associated with soleus EMG at 20%. The results support surface quadriceps muscles stimulation as a method to preferentially study heteronymous inhibition at least in healthy adults. The primary benefit of using muscle stimulation is expected to be in persons with abnormal, prolonged heteronymous excitation. These data further suggest heteronymous feedback should be evaluated with H-reflex or onto ongoing EMG of at least 20% max to identify group differences or modulation of heteronymous feedback in response to treatment or task.

Multi-muscle synergies in preparation for gait initiation in Parkinson's disease.

OBJECTIVE: We investigated changes in indices of muscle synergies prior to gait initiation and the effects of gaze shift in patients with Parkinson's disease (PD). A long-term objective of the study is to develop a method for quantitative assessment of gait-initiation problems in PD. METHODS: PD patients without clinical signs of postural instability and two control groups (age-matched and young) performed a gait initiation task in a self-paced manner, with and without a quick prior gaze shift produced by turning the head. Muscle groups with parallel scaling of activation levels (muscle modes) were identified as factors in the muscle activation space. Synergy index stabilizing center of pressure trajectory in the anterior-posterior and medio-lateral directions (indices of stability) was quantified in the muscle mode space. A drop in the synergy index in preparation to gait initiation (anticipatory synergy adjustment, ASA) was quantified. RESULTS: Compared to the control groups, PD patients showed significantly smaller synergy indices and ASA for both directions of the center of pressure shift. Both PD and age-matched controls, but not younger controls, showed detrimental effects of the prior gaze shift on the ASA indices. CONCLUSIONS: PD patients without clinically significant posture or gait disorders show impaired stability of the center of pressure and its diminished adjustment during gait initiation. SIGNIFICANCE: The indices of stability and ASA may be useful to monitor pre-clinical gait disorders, and lower ASA may be relevant to emergence of freezing of gait in PD.

Distortions of the Efferent Copy during Force Perception: A Study of Force Drifts and Effects of Muscle Vibration.

We used a finger force matching task to explore the role of efferent signals in force perception. Healthy, young participants performed accurate force production tasks at different force levels with the index and middle fingers of one hand (task-hand). They received visual feedback during an early part of each trial only. After the feedback was turned off, the force drifted toward lower magnitudes. After 5 s of the drift, the participants matched the force with the same finger pair of the other hand (match-hand). The match-hand consistently overshot the task-hand force by a magnitude invariant over the initial force levels. During force matching, both hands were lifted and lowered smoothly to estimate their referent coordinate (RC) and apparent stiffness values. These trials were performed without muscle vibration and under vibration applied to the finger/hand flexors or extensors of the task-hand or match-hand. Effects of vibration were seen in the match-hand only; they were the same during vibration of flexors and extensors. We interpret the vibration-induced effects as consequences of using distorted copies of the central commands to the task-hand during force matching. In particular, using distorted copies of the RC for the antagonist muscle group could account for the differences between the task-hand and match-hand. We conclude that efferent signals may be distorted before their participation in the perceptual process. Such distortions emerge spontaneously and may be amplified by the response of sensory endings to muscle vibration combined over both agonist and antagonist muscle groups.

Finger Force Matching and Verbal Reports: Testing Predictions of the Iso-Perceptual Manifold Concept.

We used force matching and verbal reports of finger force to explore a prediction of the iso-perceptual manifold concept, which assumes that stable percepts are associated with a manifold in the afferent-efferent space. Young subjects produced various force magnitudes with the index finger, middle finger, or both fingers together. Further, they reported the force level using a verbal scale and by matching the force with fingers of the contralateral hand. Force matching, but not verbal reports, showed larger variable errors for individual fingers in the two-finger task compared to the single-finger tasks. We discuss possible differences in afferent and efferent contributions to force perception at low and high forces based on the idea of motor control with referent coordinates for the effectors. The differences between the force matching and verbal reports are possibly related to neural circuitry differences between perceiving without action and perceiving-to-act.

Finger interdependence and unintentional force drifts: Lessons from manipulations of visual feedback.

We explored the phenomenon of unintentional finger force drift by using visual feedback on the force produced either by explicitly instructed (master) finger pairs or by non-instructed (enslaved) finger pairs. In particular, we drew contrasting predictions from two hypotheses: that force drifts represented consequences of drifts in effector referent coordinates at the level of individual fingers vs. at the level of finger modes (hypothetical variables accounting for the finger force interdependence). Subjects performed accurate force production with two fingers of a hand, index-ring or middle-little. They received visual feedback on the force produced either by the master fingers or by the other two, enslaved, fingers. The feedback scale was adjusted to ensure that the subjects did not know the difference between these two, randomly presented, conditions. Under feedback on the master finger force, enslaved force showed a consistent drift upward. Under feedback on the enslaved finger force, master force showed a consistent drift downward. The subjects were unaware of the force drifts, which could reach over 35% of the initial force magnitude. The data support the hypothesis on drifts in the referent coordinate at the level of individual digits, not finger modes, as the origin of unintentional force drifts. The consistent increase in the relative amount of force produced by the enslaved fingers suggests that the commonly used methods to quantify enslaving should include relatively brief force production tasks.

Perceptual and Motor Effects of Muscle Co-activation in a Force Production Task.

We tested several predictions of the theory of motor control with spatial referent coordinates related to effects of muscle coactivation on force production and perception. In particular, we predicted that subjects would produce unintentional force increase by finger flexors and be unaware of this force increase. Healthy subjects performed steady force production task in isometric conditions with visual feedback on the force level. They coactivated muscles of the arm trying to keep the force constant in the absence of visual feedback. This led to a consistent force increase not perceived by the subjects as reflected by their verbal reports. In contrast, when asked to match the force with the contralateral hand, adequate force matching was observed. Using the "inverse piano" apparatus confirmed no change in the referent coordinate of the fingers and an increase in its apparent stiffness. The results confirm the earlier hypothesis on the reciprocal command being hierarchically higher than the coactivation command. The observations suggest that verbal reports and force matching use different neural mechanisms of force perception; the former are dominated by sense of effort, which reflects primarily the magnitude of the reciprocal command. There were only minor differences between the dominant and non-dominant hands, likely reflecting the faster unintentional drifts of control variables in the dominant hand.

Exploring the Concept of Iso-perceptual Manifold (IPM): A Study of Finger Force-Matching Tasks.

We used force-matching tasks between the two hands to test predictions of the recently introduced scheme of perception based on the concept of iso-perceptual manifold (IPM) in the combined afferent-efferent space of neural signals. The main hypothesis was that accuracy and variability of individual finger force matching would be worse in a four-finger task compared to one-finger tasks. The subjects produced accurate force levels under visual feedback by pressing with either all four fingers or by one of the fingers of a hand (task-hand). They tried to match the total four-finger force or individual finger forces by pressing with the other hand (match-hand, no visual feedback). The match-hand consistently overshot the task-hand force during single-finger matching episodes. It showed higher inter-trial force variability during single-finger matching when the task-hand performed the four-finger task compared to trials when the task-hand performed single-finger tasks. These findings confirm our main hypothesis by showing that perception of individual finger forces can vary in multi-finger tasks within a space (IPM) corresponding to veridical perception of total force. Matching hypothetical commands to fingers, rather than finger forces, could be responsible for the consistent force overshoots. Indices of inter-trial variance affecting and unaffecting total force showed strong stabilization of total force in the task-hand but not in the match-hand in support of an earlier hypothesis on the importance of visual feedback for force stabilization. No differences were seen between the right and left hands suggesting that the dynamic dominance hypothesis may not be generalizable to perceptual phenomena.

[Effects of midodrine on symptomatic hypotension during hemodialysis]. / Efecto de la midodrina en la hipotensión sintomática en hemodiálisis.

BACKGROUND: Hypotension occurs in 20% of hemodialysis procedures. AIM: To study the effects of midodrine on hypotension during hemodialysis. PATIENTS AND METHODS: Ten patients on chronic hemodialysis and with a history of hypotension during the procedure, were studied. They received midodrine 10 mg per os or placebo during 5 dialytic procedures each, in a double blind cross over design. RESULTS: Blood pressure levels prior to dialysis were similar during the midodrine or placebo administration periods. During dialysis, systolic blood pressure fell 19.3 +/- 28 mmHg with midodrine and 23.4 +/- 28 mmHg with placebo. Diastolic blood pressure fell 7.3 +/- 11.5 mmHg with midodrine and 11.1 +/- 12 mmHg with placebo. The reduction in median arterial pressure was also less pronounced with midodrine. CONCLUSIONS: Midodrine lessens the fall in arterial pressure during hemodialysis, in patients with symptomatic hypotension.