Maria Knikou

The H-reflex as a probe: pathways and pitfalls.

The Hoffmann (or H) reflex is considered a major probe for non-invasive study of sensorimotor integration and plasticity of the central nervous system in humans. The first section of this paper reviews the neurophysiological properties of the H-reflex, which if ignored create serious pitfalls in human experimental studies. The second section reviews the spinal inhibitory circuits and neuronal pathways that can be indirectly assessed in humans using the H-reflex. The most confounding factor is that reciprocal, presynaptic, and Ib inhibition do not act in isolation during movement. Therefore, characterization of these spinal circuits should be more comprehensive, especially in cases of a neurological injury because neurophysiological findings are critical for the development of successful rehabilitation protocols. To conclude, the H-reflex is a highly sensitive reflex with an amplitude that is the result of complex neural mechanisms that act synchronously. If these limitations are recognized and addressed, the H-reflex constitutes one of the major probes to assess excitability of interneuronal circuits at rest and during movement in humans.

Effects of changes in hip joint angle on H-reflex excitability in humans

We examined the amplitude modulation of the soleus (Sol) H-reflex during controlled variations of the hip joint angle in 21 healthy adult human subjects. Hip angle variations were imposed separately, or in combination either with stimulation of the plantar skin or with electrical activation of muscle afferents from the medial gastrocnemius (MG) nerve. We found that with subjects in the supine position, flexion of the hip significantly depressed Sol H-reflex excitability, by as much as 50% of control reflex values (Ho) recorded at 10° of hip flexion. Conversely, significant facilitation of the H-reflex was observed when the hip joint was extended (10°), with amplitudes reaching 200±15.3% of Ho. Changes in H-reflex amplitude were also observed during electrical stimulation of either the foot sole or the MG nerve, when stimuli were delivered at different hip angles. Foot sole stimulation resulted in facilitation of the H-reflex with the hip extended while depression of the reflex was recorded with the hip flexed. In contrast, MG nerve stimulation at group-I muscle afferent strength resulted in a significant increase in the Sol H-reflex magnitude with the hip flexed, while during hip extension, suppression of the H-reflex was present. This study provides evidence for the existence of a spinal mechanism, determined principally by the hip joint angle, which promotes switching between inhibitory and facilitatory pathways during hip flexion and extension. The origins of such a spinal mechanism are discussed.

Neural control of locomotion and training-induced plasticity after spinal and cerebral lesions

Standing and walking require a plethora of sensorimotor interactions that occur throughout the nervous system. Sensory afferent feedback plays a crucial role in the rhythmical muscle activation pattern, as it affects through spinal reflex circuits the spinal neuronal networks responsible for inducing and maintaining rhythmicity, drives short-term and long-term re-organization of the brain and spinal cord circuits, and contributes to recovery of walking after locomotor training. Therefore, spinal circuits integrating sensory signals are adjustable networks with learning capabilities. In this review, I will synthesize the mechanisms underlying phase-dependent modulation of spinal reflexes in healthy humans as well as those with spinal or cerebral lesions along with findings on afferent regulation of spinal reflexes and central pattern generator in reduced animal preparations. Recovery of walking after locomotor training has been documented in numerous studies but the re-organization of spinal interneuronal and cortical circuits need to be further explored at cellular and physiological levels. For maximizing sensorimotor recovery in people with spinal or cerebral lesions, a multidisciplinary approach (rehabilitation, pharmacology, and electrical stimulation) delivered during various sensorimotor constraints is needed.

Plantar Cutaneous Afferents Normalize the Reflex Modulation Patterns During Stepping in Chronic Human Spinal Cord Injury

Plantar cutaneous afferent transmission is critical for recovery of locomotion in spinalized animals, whereas a phase-dependent reflex modulation is apparent during fictive or real locomotion. In nine people with a chronic spinal cord injury (SCI) the effects of foot sole stimulation on the soleus H-reflex and tibialis anterior (TA) flexion reflex modulation patterns during assisted stepping were established on different days. The soleus H-reflex was elicited by posterior tibial nerve stimulation followed by a supramaximal stimulus 100 ms after the test H-reflex to control for movement of recording electrodes. The flexion reflex was evoked by sural nerve stimulation with a 30-ms pulse train, recorded from the ipsilateral TA muscle, and elicited at 1.2- to twofold the reflex threshold. During assisted stepping, spinal reflexes were conditioned by percutaneous stimulation of the ipsilateral metatarsals at threefold perceptual threshold with a 20-ms pulse train delivered at 9- to 11-ms conditioning-test intervals. Stimuli were randomly dispersed across the step cycle, which was divided into 16 equal bins. The conditioned soleus H-reflex was significantly facilitated at midstance and depressed during midswing when compared with the unconditioned soleus H-reflex recorded during stepping. Foot sole stimulation induced a significant facilitation of the long-latency TA flexion reflex before, during, and after stance-to-swing transition when compared with the unconditioned long-latency TA flexion reflex during stepping. This study provides evidence that plantar cutaneous afferents remarkably influence the soleus H-reflex and TA flexion reflex modulation patterns during stepping and support that actions of plantar cutaneous afferents onto spinal interneuronal circuits engaged in locomotion are manifested in a phase-dependent manner in chronic SCI subjects.

Locomotor training improves premotoneuronal control after chronic spinal cord injury

Spinal inhibition is significantly reduced after spinal cord injury (SCI) in humans. In this work, we examined if locomotor training can improve spinal inhibition exerted at a presynaptic level. Sixteen people with chronic SCI received an average of 45 training sessions, 5 days/wk, 1 h/day. The soleus H-reflex depression in response to low-frequency stimulation, presynaptic inhibition of soleus Ia afferent terminals following stimulation of the common peroneal nerve, and bilateral EMG recovery patterns were assessed before and after locomotor training. The soleus H reflexes evoked at 1.0, 0.33, 0.20, 0.14, and 0.11 Hz were normalized to the H reflex evoked at 0.09 Hz. Conditioned H reflexes were normalized to the associated unconditioned H reflex evoked with subjects seated, while during stepping both H reflexes were normalized to the maximal M wave evoked after the test H reflex at each bin of the step cycle. Locomotor training potentiated homosynaptic depression in all participants regardless the type of the SCI. Presynaptic facilitation of soleus Ia afferents remained unaltered in motor complete SCI patients. In motor incomplete SCIs, locomotor training either reduced presynaptic facilitation or replaced presynaptic facilitation with presynaptic inhibition at rest. During stepping, presynaptic inhibition was modulated in a phase-dependent manner. Locomotor training changed the amplitude of locomotor EMG excitability, promoted intralimb and interlimb coordination, and altered cocontraction between knee and ankle antagonistic muscles differently in the more impaired leg compared with the less impaired leg. The results provide strong evidence that locomotor training improves premotoneuronal control after SCI in humans at rest and during walking.

Plasticity of Corticospinal Neural Control after Locomotor Training in Human Spinal Cord Injury

Spinal lesions substantially impair ambulation, occur generally in young and otherwise healthy individuals, and result in devastating effects on quality of life. Restoration of locomotion after damage to the spinal cord is challenging because axons of the damaged neurons do not regenerate spontaneously. Body-weight-supported treadmill training (BWSTT) is a therapeutic approach in which a person with a spinal cord injury (SCI) steps on a motorized treadmill while some body weight is removed through an upper body harness. BWSTT improves temporal gait parameters, muscle activation patterns, and clinical outcome measures in persons with SCI. These changes are likely the result of reorganization that occurs simultaneously in supraspinal and spinal cord neural circuits. This paper will focus on the cortical control of human locomotion and motor output, spinal reflex circuits, and spinal interneuronal circuits and how corticospinal control is reorganized after locomotor training in people with SCI. Based on neurophysiological studies, it is apparent that corticospinal plasticity is involved in restoration of locomotion after training. However, the neural mechanisms underlying restoration of lost voluntary motor function are not well understood and translational neuroscience research is needed so patient-orientated rehabilitation protocols to be developed.

Reduced reciprocal inhibition during assisted stepping in human spinal cord injury

The aim of this study was to establish the modulation pattern of the reciprocal inhibition exerted from tibialis anterior (TA) group I afferents onto soleus motoneurons during body weight support (BWS) assisted stepping in people with spinal cord injury (SCI). During assisted stepping, the soleus H-reflex was conditioned by percutaneous stimulation of the ipsilateral common peroneal nerve at one fold TA M-wave motor threshold with a single pulse delivered at a short conditioning-test interval. To counteract movement of recording and stimulating electrodes, a supramaximal stimulus at 80-100 ms after the test H-reflex was delivered. Stimuli were randomly dispersed across the step cycle which was divided into 16 equal bins. The conditioned soleus H-reflex was significantly facilitated throughout the stance phase, while during swing no significant changes on the conditioned H-reflex were observed when compared to the unconditioned soleus H-reflex recorded during stepping. Spontaneous clonic activity in triceps surae muscle occurred in multiple phases of the step cycle at a mean frequency of 7 Hz for steps with and without stimulation. This suggests that electrical excitation of TA and soleus group Ia afferents did not contribute to manifestation of ankle clonus. Absent reciprocal inhibition is likely responsible for lack of soleus H-reflex depression in swing phase observed in these patients. The pronounced reduced reciprocal inhibition in stance phase may contribute to impaired levels of co-contraction of antagonistic ankle muscles. Based on these findings, we suggest that rehabilitation should selectively target to transform reciprocal facilitation to inhibition through computer controlled reflex conditioning protocols.

Soleus H-Reflex Gain, Threshold, and Amplitude as Function of Body Posture and Load in Spinal Cord Intact and Injured Subjects

In this study, we established parameters of the soleus H-reflex excitability in response to changes of posture and load in 8 chronic spinal cord injured (SCI) and 10 spinal-intact subjects. The soleus H-reflex recruitment curve was established in all subjects while they were supine, seated, and standing on a stable treadmill. During standing, body weight support (BWS) was provided via an upper body harness and ranged in SCI subjects from 20%–50% and in spinal-intact subjects was set at 0% and 50%. Stimuli corresponding to the H-threshold (Hth), maximal H-reflex amplitude (Hmax), and 50% of Hmax as well as the reflex gain were estimated based on a sigmoid function of the ascending limb of the soleus H-reflex recruitment curve. The soleus H-reflex gain, Hmax amplitude, and stimuli corresponding to Hth, 50% of Hmax, and Hmax were increased in SCI subjects regardless of the body position and loading. Further, the reflex gain was not modulated appropriately during conditions of weight bearing in SCI subjects. Impaired spinal reflex excitability in SCI subjects is accompanied by changes of the H-reflex recruitment curve parameters regardless of presence or absence of body loading.

Soleus H-reflex phase-dependent modulation is preserved during stepping within a robotic exoskeleton.

OBJECTIVE To investigate to what extent the phase-dependent modulation of the soleus H-reflex is preserved when bilateral leg movements are electromechanically driven by a robotic exoskeleton at different levels of body weight support (BWS) in healthy subjects. METHODS The soleus H-reflex was elicited by posterior tibial nerve stimulation with a 1-ms single pulse at an intensity that the M-waves ranged from 4% to 9% of the maximal M-wave across subjects. Stimuli were randomly dispersed across the step cycle which was divided into 16 equal bins. At each bin, a maximal M-wave was elicited 100 ms after the test H-reflex and was used to normalize the associated M-wave and H-reflex. Electromyographic (EMG) activity from major hip, knee, and ankle muscles was recorded with surface bipolar electrodes. For each subject and muscle, the integrated EMG profile was established and plotted as a function of the step cycle phases. The H-reflex gain was determined as the slope of the relationship between the H-reflex and soleus EMG amplitudes at 100 ms before the H-reflex for each bin. RESULTS During robotic assisted stepping, the phase-dependent soleus H-reflex modulation pattern was preserved and was similar at 25% and 50% BWS, a linear relationship between soleus H-reflex amplitude and background activity was found, and the reflex gain did not change with alterations of the BWS level. EMG amplitudes were smaller at 50% compared to 25% BWS. CONCLUSIONS Body unloading, decreased EMG amplitude of ankle extensors, and reduced ankle movement are not key factors for the soleus H-reflex phasic excitability to be manifested. SIGNIFICANCE Robotic devices are utilized for rehabilitation of gait in neurological disorders. Based on our findings, spinal interneuronal circuits involved in the phase-dependent modulation of the soleus H-reflex will be engaged in a physiological manner during robotic assisted stepping in neurological disorders.

Neural coupling between the upper and lower limbs in humans

The aim of this study was to establish the effects of active sinusoidal ipsilateral and contralateral upper limb flexion, extension, abduction, and adduction with elbows extended on the right soleus H-reflex with subjects seated and standing. Reflex effects were also established when both arms moved synchronously in a reciprocal pattern with elbows flexed in seated and standing subjects. Sinusoidal arm movements were timed to a metronome and performed at 0.2 Hz. Soleus H-reflexes were elicited only once (every 4s) in every movement cycle of the upper limbs. Position of arms, and activity of shoulder muscles were recorded through twin-axis goniometers and surface electromyography (EMG), respectively. We found that in seated subjects, regardless the direction of the active movement or the upper limb being moved, the soleus H-reflex was depressed. In standing subjects, a reflex depression was observed during extension, abduction, and adduction of the ipsilateral and contralateral upper limbs. Muscles were active during arm flexion and abduction in all directions of arm movement with subjects either seated or standing. It is suggested that arm movement might be incorporated in the rehabilitation training of people with a supraspinal or spinal cord lesion, since it can benefit motor recovery by decreasing spinal reflex excitability of the legs in these patients.