Allison Hyngstrom

Intrinsic electrical properties of spinal motoneurons vary with joint angle

The dendrites of spinal motoneurons amplify synaptic inputs to a marked degree through persistent inward currents (PICs). Dendritic amplification is subject to neuromodulatory control from the brainstem by axons releasing the monoamines serotonin and norepinephrine; however, the monoaminergic projection to the cord is diffusely organized and does not allow independent adjustment of amplification in different motor pools. Using in vivo voltage-clamp techniques, here we show that dendritic PICs in ankle extensor motoneurons in the cat are reduced about 50% by small rotations (±10°) of the ankle joint. This reduction is primarily due to reciprocal inhibition, a tightly focused input shared only among strict muscle antagonists. These results demonstrate how a specific change in limb position can regulate intrinsic cellular properties set by a background of diffuse descending neuromodulation.

Active properties of motoneurone dendrites: Diffuse descending neuromodulation, focused local inhibition

The dendrites of spinal motoneurones are highly active, generating a strong persistent inward current (PIC) that has an enormous impact on processing of synaptic input. The PIC is subject to regulation by descending neuromodulatory systems releasing the monoamines serotonin and noradrenaline. At high monoaminergic drive levels, the PIC dominates synaptic integration, generating an intrinsic dendritic current that is as much as 5‐fold larger than the current entering via synapses. Without the PIC, motoneurone excitability is very low. Presumably, this descending control of the synaptic integration via the PIC is used to adjust the excitability (gain) of motoneurones for different motor tasks. A problem with this gain control is that monoaminergic input to the cord is very diffuse, affecting many motor pools simultaneously, probably including both agonists and antagonists. The PIC is, however, exquisitely sensitive to the reciprocal inhibition mediated by length sensitive muscle spindle Ia afferents and Ia interneurones. Reciprocal inhibition is tightly focused, shared only between strict mechanical antagonists, and thus can act to ‘sculpt’ specific movement patterns out of a background of diffuse neuromodulation. Thus it is likely that motoneurone gain is set by the interaction between diffuse descending neuromodulation and specific and focused local synaptic inhibitory circuits.

Movement-related receptive fields of spinal motoneurones with active dendrites

The primary control of spinal motoneurone excitability is mediated by descending monoaminergic systems, which have diffuse effects on multiple motor pools. Much of the sensory input evoked by movement is also distributed broadly to multiple joints. The muscle spindle Ia afferent system, however, is sharply focused, with Ia excitation restricted to close synergists and Ia reciprocal inhibition only shared between antagonists acting at a single joint. We studied the interaction of neuromodulatory and sensory inputs in determining the movement‐related receptive field (MRRF) of motoneurones during passive joint movements of the cat hindlimb. In a decerebrate preparation with tonic monoaminergic input to the cord, the MRRFs tended to be focused for the ankle and knee extensor motor pools studied. Ankle rotation produced larger synaptic currents in ankle extensors than knee or hip rotations and knee rotation dominated input to the knee extensors. The persistent inward current (PIC) in motoneurone dendrites, which is facilitated by monoaminergic input, amplified the MRRF about 2‐fold, consistent with its effects on other inputs. Acute spinal transaction markedly broadened MRRFs, with hip rotation generating large currents in both ankle and knee extensors. Spinalization also eliminated amplification of MRRFs, as expected from elimination of descending monoaminergic input. Ia reciprocal inhibition is very effective in suppressing dendritic PICs and thus provides a local and specific PIC control system to oppose the diffuse PIC facilitation from descending monoaminergic systems. The focused MRRF seen in the intact cord state would allow reciprocal inhibition to fulfil this role without undue interference from multijoint input from other afferent systems.

Summation of Excitatory and Inhibitory Synaptic Inputs by Motoneurons With Highly Active Dendrites

We investigated summation of steady excitatory and inhibitory inputs in spinal motoneurons using an in vivo preparation, the decerebrate cat, in which neuromodulatory input from the brain stem facilitated a strong persistent inward current (PIC) in dendritic regions. This dendritic PIC amplified both excitatory and inhibitory synaptic currents two- to threefold, but within different voltage ranges. Amplification of excitatory synaptic current peaked at voltage-clamp holding potentials near spike threshold (about -55 to -50 mV), whereas amplification of inhibitory current peaked at significantly more depolarized levels (about -45 to -40 mV). Thus the linear sum of excitatory and inhibitory currents tended to vary from net excitatory to net inhibitory as holding potential was depolarized. The actual summed currents, however, diverged from the predicted linear currents. At the peak of excitation, summation averaged about 15% sublinear (actual sum was less positive than the linear sum). In contrast, at the peak of inhibition, summation averaged about 18% supralinear (actual more positive than linear). Moreover, these nonlinear effects were substantially larger in cells where the variation from peak excitation to peak inhibition for linear summation was larger. When descending neuromodulatory input was eliminated by acute spinalization, PIC amplification was not observed and summation tended to be either sublinear or approximately linear, depending on input source. Overall, in cells with strong PICs, nonlinear summation of excitation and inhibition does occur, but this nonlinearity results in a more consistent relationship between membrane potential and the summed excitatory and inhibitory current.

Push-Pull Control of Motor Output

Inhibition usually decreases input–output excitability of neurons. If, however, inhibition is coupled to excitation in a push–pull fashion, where inhibition decreases as excitation increases, neuron excitability can be increased. Although the presence of push–pull organization has been demonstrated in single cells, its functional impact on neural processing depends on its effect on the system level. We studied push–pull in the motor output stage of the feline spinal cord, a system that allows independent control of inhibitory and excitatory components. Push–pull organization was clearly present in ankle extensor motoneurons, producing increased peak-to-peak modulation of synaptic currents. The effect at the system level was equally strong. Independent control of the inhibitory component showed that the stronger the background of inhibition, the greater the peak force production. This illustrates the paradox at the heart of push–pull organization: increased force output can be achieved by increasing background inhibition to provide greater disinhibition.

Stroke-related changes in neuromuscular fatigue of the hip flexors and functional implications.

ObjectiveThe aim of this study was to compare stroke-related changes in hip flexor neuromuscular fatigue of the paretic leg during a sustained isometric submaximal contraction with those of the nonparetic leg and controls and to correlate fatigue with clinical measures of function. DesignHip torques were measured during a fatiguing hip flexion contraction at 20% of the hip flexion maximal voluntary contraction in the paretic and nonparetic legs of 13 people with chronic stroke and 10 age-matched controls. In addition, the participants with stroke performed a fatiguing contraction of the paretic leg at the absolute torque equivalent to 20% maximal voluntary contraction of the nonparetic leg and were tested for self-selected walking speed (10-m Walk Test) and balance (Berg). ResultsWhen matching the nonparetic target torque, the paretic hip flexors had a shorter time to task failure compared with the nonparetic leg and controls (P < 0.05). The time to failure of the paretic leg was inversely correlated with the reduction of hip flexion maximal voluntary contraction torque. Self-selected walking speed was correlated with declines in torque and steadiness. Berg-Balance scores were inversely correlated with the force fluctuation amplitude. ConclusionsFatigue and precision of contraction are correlated with walking function and balance after stroke.

Abnormal Volitional Hip Torque Phasing and Hip Impairments in Gait Post Stroke

The purpose of this study was to quantify how volitional control of hip torque relates to walking function poststroke. Volitional phasing of hip flexion and extension torques was assessed using a load-cell-instrumented servomotor drive system in 11 chronic stroke subjects and 5 age-matched controls. Hips were oscillated from approximately 40 degrees of hip flexion to 10 degrees of hip extension at a frequency of 0.50 Hz during three movement conditions [hips in phase (IP), 180 degrees out of phase (OP), and unilateral hip movement (UN)] while the knees and ankles were held stationary. The magnitude and phasing of hip, knee, and ankle torques were measured during each movement condition. Surface electromyography was measured throughout the legs. Over ground gait analysis was done for all stroke subjects. During robotic-assisted movement conditions, the paretic limb produced peak hip torques when agonist hip musculature was stretched instead of midway through the movement as seen in the nonparetic and control limbs (P < 0.012). However, mean torque magnitudes of the paretic and nonparetic limbs were not significantly different. Abnormalities of paretic hip torque phasing were more pronounced during bilateral movement conditions and were associated with quadriceps overactivity. The magnitude of flexion torque produced during maximal hip extension was correlated with the Fugl Meyer Score, self-selected walking speed, and maximal hip extension during over ground walking. These results suggest that hyperexcitable stretch reflexes in the paretic limb impair coordinated hip torque phasing and likely interfere with walking function post stroke.

Functional Implications of Impaired Control of Submaximal Hip Flexion Following Stroke

Introduction: We quantified submaximal torque regulation during low to moderate intensity isometric hip flexion contractions in individuals with stroke and the associations with leg function. Methods: Ten participants with chronic stroke and 10 controls performed isometric hip flexion contractions at 5%, 10%, 15%, 20%, and 40% of maximal voluntary contraction (MVC) in paretic, nonparetic, and control legs. Results: Participants with stroke had larger torque fluctuations (coefficient of variation, CV), for both the paretic and nonparetic legs, than controls (P < 0.05) with the largest CV at 5% MVC in the paretic leg (P < 0.05). The paretic CV correlated with walking speed (r2 = 0.54) and Berg Balance Score (r2 = 0.40). At 5% MVC, there were larger torque fluctuations in the contralateral leg during paretic contractions compared with the control leg. Conclusions: Impaired low‐force regulation of paretic leg hip flexion can be functionally relevant and related to control versus strength deficits poststroke. Muscle Nerve 49: 225–232, 2014

Influence of visual feedback on dynamic balance control in chronic stroke survivors

Chronic stroke survivors have an increased incidence of falls during walking, suggesting changes in dynamic balance control post-stroke. Despite this increased incidence of falls during walking, balance control is often studied only in standing. The purpose of this study was to quantify deficits in dynamic balance control during walking, and to evaluate the influence of visual feedback on this control in stroke survivors. Ten individuals with chronic stroke, and ten neurologically intact individuals participated in this study. Walking performance was assessed while participants walked on an instrumented split-belt treadmill with different types of visual feedback. Dynamic balance control was quantified using both the extent of center of mass (COM) movement in the frontal plane over a gait cycle (COM sway), and base of support (step width). Stroke survivors walked with larger COM sway and wider step widths compared to controls. Despite these baseline differences, both groups walked with a similar ratio of step width to COM sway (SW/COM). Providing a stationary target with a laser reference of body movement reduced COM sway only in the stroke group, indicating that visual feedback of sway alters dynamic balance control post-stroke. These results demonstrate that stroke survivors attempt to maintain a similar ratio of step width to COM movement, and visual cues can be used to help control COM movement during walking post-stroke.

The stroke-related effects of hip flexion fatigue on over ground walking

Individuals post stroke often rely more on hip flexors for limb advancement during walking due to distal weakness but the effects of muscle fatigue in this group is not known. The purpose of this study was to quantify how stroke affects the influence of hip flexor fatigue on over ground walking kinematics and performance and muscle activation. Ten individuals with chronic stroke and 10 without stroke (controls) participated in the study. Maximal walking speed, walking distance, muscle electromyograms (EMG), and lower extremity joint kinematics were compared before and after dynamic, submaximal fatiguing contractions of the hip flexors (30% maximal load) performed until failure of the task. Task duration and decline in hip flexion maximal voluntary contraction (MVC) and power were used to assess fatigue. The stroke and control groups had similar task durations and percent reductions in MVC force following fatiguing contractions. Compared with controls, individuals with stroke had larger percent reductions in maximal walking speed, greater decrements in hip range of motion and peak velocity during swing, greater decrements in ankle velocity and lack of modulation of hip flexor EMG following fatiguing dynamic hip flexion contractions. For a given level of fatigue, the impact on walking function was more profound in individuals with stroke than neurologically intact individuals, and a decreased ability to up regulate hip flexor muscle activity may contribute. These data highlight the importance of monitoring the effect of hip flexor muscle activity during exercise or performance of activities of daily living on walking function post stroke.