The evaluation of tactile dysfunction in the hand in type 1 diabetes: a novel method based on haptics.

AIMS: We present an innovative method based on haptics for the evaluation of the sense of touch in the hand, in people affected by type 1 diabetes. METHODS: Forty individuals affected by diabetes and 20 healthy controls took part in the study; the diabetes group was further divided into two subgroups based on vibration sensitivity in the lower limb. By means of a novel haptic device, tactile sensitivity in the fingertip was measured as the ability of the participants to discriminate slip motion speed. RESULTS: Tactile sensitivity was significantly lower in individuals affected by diabetes as compared to controls. Depending on the subgroup, the difference from the controls was equal to 0.11 (95% CI from 0.029 to 0.186) and to 0.267 (95% CI from 0.198 to 0.336). Within the diabetes group, tactile sensitivity correlated with vibration sensitivity in the upper (p = 0.001) and lower limb (p = 0.003). A significant relationship between nerve conduction parameters and tactile sensitivity was found (p = 0.03). Finally, we combined the different predictors (clinical, vibratory and electroneurography data) by using cluster analysis; tactile sensitivity was found to be significantly different between different clusters (p = 0.004). CONCLUSIONS: Early signs of tactile dysfunction in the hand were found in individuals affected by diabetes, even in absence of diabetic neuropathy. The protocol presented in this study is a promising tool for the assessment of tactile dysfunction in the hand in people affected by type 1 diabetes.

Spinal motoneurons of the human newborn are highly synchronized during leg movements.

Motoneurons of neonatal rodents show synchronous activity that modulates the development of the neuromuscular system. However, the characteristics of the activity of human neonatal motoneurons are largely unknown. Using a noninvasive neural interface, we identified the discharge timings of individual spinal motoneurons in human newborns. We found highly synchronized activities of motoneurons of the tibialis anterior muscle, which were associated with fast leg movements. Although neonates' motor units exhibited discharge rates similar to those of adults, their synchronization was significantly greater than in adults. Moreover, neonatal motor units showed coherent oscillations in the delta band, which is directly translated into force generation. These results suggest that motoneuron synchronization in human neonates might be an important mechanism for controlling fast limb movements, such as those of primitive reflexes. In addition to help revealing mechanisms of development, the proposed neural interface might monitor children at risk of developing motor disorders.

Locomotor patterns during obstacle avoidance in children with cerebral palsy.

We investigated how early injuries to developing brain affect the interaction of locomotor patterns with the voluntary action required by obstacle clearance. This task requires higher cognitive load and specific anticipatory sensorimotor integration than more automated steady-state gait. To this end, we compared the adaptive gait patterns during obstacle clearance in 40 children with cerebral palsy (CP) (24 diplegic, 16 hemiplegic, 2-12 yr) and 22 typically developing (TD) children (2-12 yr) by analyzing gait kinematics, joint moments during foot elevation, electromyographic (EMG) activity of 11 pairs of bilateral muscles, and muscle modules evaluated by factorization of the EMG signals. The results confirmed generally slower task performance, plus difficulty in motor planning and control in CP. Thus ~30% of diplegic children failed to perform the task. Children with CP demonstrated higher foot lift, smaller range of motion of distal segments, difficulties in properly activating the hamstring muscles at liftoff, and a modified hip strategy when elevating the trailing limb. Basic muscle modules were generally roughly similar to TD patterns, though they showed a limited adaptation. Thus a distinct activation burst in the adaptable muscle module timed to the voluntary task (liftoff) was less evident in CP. Children with CP also showed prolonged EMG burst durations. Impaired obstacle task performance may reflect impaired or less adaptable supraspinal and spinal control of gait when a locomotor task is superimposed with the voluntary movement. Neurorehabilitation of gait in CP may thus be beneficial by adding voluntary tasks such as obstacle clearance during gait performance.NEW & NOTEWORTHY Previous studies mainly evaluated the neuromuscular pattern generation in cerebral palsy (CP) during unobstructed gait. Here we characterized impairments in the obstacle task performance associated with a limited adaptation of the task-relevant muscle module timed to the foot lift during obstacle crossing. Impaired task performance in children with CP may reflect basic developmental deficits in the adaptable control of gait when the locomotor task is superimposed with the voluntary movement.

Neuromechanical adjustments when walking with an aiding or hindering horizontal force.

PURPOSE: Walking against a constant horizontal traction force which either hinders or aids the motion of the centre of mass of the body (COM) will create a discrepancy between the positive and negative work being done by the muscles and may thus affect the mechanics and energetics of walking. We aimed at investigating how this imbalance affects the exchange between potential and kinetic energy of the COM and how its dynamics is related to specific spatiotemporal organisation of motor pool activity in the spinal cord. To understand if and how the spinal cord activation may be associated with COM dynamics, we also compared the neuromechanical adjustments brought on by a horizontal force with published data about those brought on by a slope. METHODS: Ten subjects walked on a treadmill at different speeds with different traction forces. We recorded kinetics, kinematics, and electromyographic activity of 16 lower-limb muscles and assessed the spinal locomotor output by mapping them onto the rostrocaudal location of the motoneuron pools. RESULTS: When walking with a hindering force, the major part of the exchange between potential and kinetic energy of the COM occurs during the first part of stance, whereas with an aiding force exchanges increase during the second part of stance. Those changes occur since limb and trunk orientations remain aligned with the average orientation of the ground reaction force vector. Our results also show the sacral motor pools decreased their activity with an aiding force and increased with a hindering one, whereas the lumbar motor pools increased their engagement both with an aiding and a hindering force. CONCLUSION: Our findings suggest that applying a constant horizontal force results in similar modifications of COM dynamics and spinal motor output to those observed when walking on slopes, consistent with common principles of motor pool functioning and biomechanics of locomotion.

Differential activation of lumbar and sacral motor pools during walking at different speeds and slopes.

Organization of spinal motor output has become of interest for investigating differential activation of lumbar and sacral motor pools during locomotor tasks. Motor pools are associated with functional grouping of motoneurons of the lower limb muscles. Here we examined how the spatiotemporal organization of lumbar and sacral motor pool activity during walking is orchestrated with slope of terrain and speed of progression. Ten subjects walked on an instrumented treadmill at different slopes and imposed speeds. Kinetics, kinematics, and electromyography of 16 lower limb muscles were recorded. The spinal locomotor output was assessed by decomposing the coordinated muscle activation profiles into a small set of common factors and by mapping them onto the rostrocaudal location of the motoneuron pools. Our results show that lumbar and sacral motor pool activity depend on slope and speed. Compared with level walking, sacral motor pools decrease their activity at negative slopes and increase at positive slopes, whereas lumbar motor pools increase their engagement when both positive and negative slope increase. These findings are consistent with a differential involvement of the lumbar and the sacral motor pools in relation to changes in positive and negative center of body mass mechanical power production due to slope and speed.NEW & NOTEWORTHY In this study, the spatiotemporal maps of motoneuron activity in the spinal cord were assessed during walking at different slopes and speeds. We found differential involvement of lumbar and sacral motor pools in relation to changes in positive and negative center of body mass power production due to slope and speed. The results are consistent with recent findings about the specialization of neuronal networks located at different segments of the spinal cord for performing specific locomotor tasks.

Touch as an auxiliary proprioceptive cue for movement control.

Recent studies extended the classical view that touch is mainly devoted to the perception of the external world. Perceptual tasks where the hand was stationary demonstrated that cutaneous stimuli from contact with objects provide the illusion of hand displacement. Here, we tested the hypothesis that touch provides auxiliary proprioceptive feedback for guiding actions. We used a well-established perceptual phenomenon to dissociate the estimates of reaching direction from touch and musculoskeletal proprioception. Participants slid their fingertip on a ridged plate to move toward a target without any visual feedback on hand location. Tactile motion estimates were biased by ridge orientation, inducing a systematic deviation in hand trajectories in accordance with our hypothesis. Results are in agreement with an ideal observer model, where motion estimates from different somatosensory cues are optimally integrated for the control of movement. These outcomes shed new light on the interplay between proprioception and touch in active tasks.

Locomotor coordination in patients with Hereditary Spastic Paraplegia.

Locomotion is a complex behaviour that requires the coordination of multiple body segments and muscle groups. Here we investigated how the weakness and spasticity in individuals with Hereditary Spastic Paraplegia (HSP) affect the coordination patterns of the lower limbs. We analysed kinematics and electromyographic (EMG) activity from 12 leg muscles in 21 persons with HSP and 20 control subjects at matched walking speeds. To assess the locomotor coordination, we examined the covariation between thigh, shank and foot elevation angles by means of principal component analysis and the modular organization of EMG patterns using the non-negative matrix factorization algorithm. The characteristic features of the HSP gait consisted in changes of the elevation angles covariation, the shape of the gait loop, reduced range of motion of the distal segments and significantly lower foot lift. The EMG factorization analysis revealed a comparable structure of the motor output between HSP and control groups, but significantly wider basic temporal patterns associated with muscles innervated from the sacral spinal segments in HSP. Overall, the applied methodology highlighted the impact of the corticospinal degeneration and spasticity on the coordination of distal limb segments and basic muscle modules associated with distal spinal segments.

Reduced betweenness centrality of a sensory-motor vestibular network in subclinical agoraphobia.

Agoraphobic patients feel dizzy in crowded open spaces and respond to this symptom with excessive fear and avoidance. These clinical features show great similitude with the newly defined syndrome of persistent postural perceptual dizziness (PPPD). Patients with PPPD show decreased activity and connectivity in regions of the vestibular cortex. Due to the great overlap between these two conditions, we hypothesized that individuals with sub-clinical agoraphobia would show reduction in the connectivity features of these regions. We selected a group of healthy individuals from the Human Connectome Project that self-reported agoraphobia episodes, and compared it with a control group. We accurately matched the two groups for psychological measures and personality traits in order to study the neural correlates of vestibular symptoms independently of possible psychiatric vulnerabilities. We found that the agoraphobia group showed reduced betweenness centrality of a network encompassing key regions of the vestibular cortex. Dysfunctions of the vestibular cortex may explain the dizziness symptom for a disorder previously labelled as psychogenic.

Structural connectome of the human vestibular, pre-motor, and navigation network.

The aim of this study is to characterize modules and hubs within the multimodal vestibular system and, particularly, to test the centrality of posterior peri-sylvian regions. Structural connectivity matrices from 50 unrelated healthy right-handed subjects from the Human Connectome Project (HCP) database were analyzed using multishell diffusion-weighted data, probabilistic tractography (constrained spherical-deconvolution informed filtering of tractograms) in combination with subject-specific grey matter parcellations. Network nodes included parcellated regions within the vestibular, pre-motor and navigation system. Module calculation produced two and three modules in the right and left hemisphere, respectively. On the right, regions were grouped into a vestibular and pre-motor module, and into a visual-navigation module. On the left this last module was split into an inferior and superior component. In the thalamus, a region comprising the mediodorsal and anterior complex, and lateral and inferior pulvinar, was included in the ipsilateral navigation module, while the remaining thalamus was clustered with the ipsilateral vestibular pre-motor module. Hubs were located bilaterally in regions encompassing the inferior parietal cortex and the precuneus. This analysis revealed a dorso-lateral path within the multi-modal vestibular system related to vestibular / motor control, and a ventro-medial path related to spatial orientation / navigation. Posterior peri-sylvian regions may represent the main hubs of the whole modular network.

Kinematic patterns while walking on a slope at different speeds.

During walking, the elevation angles of the thigh, shank, and foot (i.e., the angle between the segment and the vertical) covary along a characteristic loop constrained on a plane. Here, we investigate how the shape of the loop and the orientation of the plane, which reflect the intersegmental coordination, change with the slope of the terrain and the speed of progression. Ten subjects walked on an inclined treadmill at different slopes (between -9° and +9°) and speeds (from 0.56 to 2.22 m/s). A principal component analysis was performed on the covariance matrix of the thigh, shank, and foot elevation angles. At each slope and speed, the variance accounted for by the two principal components was >99%, indicating that the planar covariation is maintained. The two principal components can be associated to the limb orientation (PC1*) and the limb length (PC2*). At low walking speeds, changes in the intersegmental coordination across slopes are characterized mainly by a change in the orientation of the covariation plane and in PC2* and to a lesser extent, by a change in PC1*. As speed increases, changes in the intersegmental coordination across slopes are more related to a change in PC1 *, with limited changes in the orientation of the plane and in PC 2*. Our results show that the kinematic patterns highly depend on both slope and speed. NEW & NOTEWORTHY In this paper, changes in the lower-limb intersegmental coordination during walking with slope and speed are linked to changes in the trajectory of the body center of mass. Modifications in the kinematic pattern with slope depend on speed: at slow speeds, the net vertical displacement of the body during each step is related to changes in limb length and orientation. When speed increases, the vertical displacement is mostly related to a change in limb orientation.

Early manifestation of arm-leg coordination during stepping on a surface in human neonates.

The accomplishment of mature locomotor movements relies upon the integrated coordination of the lower and upper limbs and the trunk. Human adults normally swing their arms and a quadrupedal limb coordination persists during bipedal walking despite a strong corticospinal control of the upper extremities that allows to uncouple this connection during voluntary activities. Here we investigated arm-leg coordination during stepping responses on a surface in human neonates. In eight neonates, we found the overt presence of alternating arm-leg oscillations, the arms moving up and down in alternation with ipsilateral lower limb movements. These neonates moved the diagonal limbs together, and the peak of the arm-to-trunk angle (i.e., maximum vertical excursion of the arm) occurred around the end of the ipsilateral stance phase, as it occurs during typical adult walking. Although episodes of arm-leg coordination were sporadic in our sample of neonates, their presence provides significant evidence for a neural coupling between the upper and lower limbs during early ontogenesis of locomotion in humans.

Differential changes in the spinal segmental locomotor output in Hereditary Spastic Paraplegia.

OBJECTIVE: A comprehensive treatment of Hereditary Spastic Paraplegia (HSP) should consider the specific pathophysiological changes in the spinal cord. Here we reported a detailed characterization of the spinal motoneuronal output in HSP during locomotion. METHODS: We recorded kinematics and electromyographic (EMG) activity of 12 leg muscles in 29 patients with pure forms of HSP and compared them with 30 controls while walking at matched speeds. We assessed the spinal locomotor output by evaluating EMG patterns and by mapping them onto the rostrocaudal location of the spinal motoneuron pools. RESULTS: The activity profiles of muscles innervated from the sacral segments were significantly wider in patients. Similarly, spinal maps revealed a tendency for spreading the main loci of activation, involving initially the sacral segments and, at more severe stages, the lumbar segments. CONCLUSIONS: The degeneration of the corticospinal tract in HSP is associated with a widening of spinal locomotor output spreading from caudal to rostral segments. SIGNIFICANCE: The findings highlight pathophysiologically relevant differential changes in the spinal locomotor output in HSP related to the specific innervation of muscles in the spinal cord, and might be helpful for developing future therapeutic strategies and identifying physiological markers of the disease.

Corrigendum: Foot Placement Characteristics and Plantar Pressure Distribution Patterns during Stepping on Ground in Neonates.

[This corrects the article on p. 784 in vol. 8, PMID: 29066982.].

Foot Placement Characteristics and Plantar Pressure Distribution Patterns during Stepping on Ground in Neonates.

Stepping on ground can be evoked in human neonates, though it is rather irregular and stereotyped heel-to-toe roll-over pattern is lacking. Such investigations can provide insights into the role of contact- or load-related proprioceptive feedback during early development of locomotion. However, the detailed characteristics of foot placements and their association with motor patterns are still incompletely documented. We elicited stepping in 33 neonates supported on a table. Unilateral limb kinematics, bilateral plantar pressure distribution and EMG activity from up to 11 ipsilateral leg muscles were recorded. Foot placement characteristics in neonates showed a wide variation. In ~25% of steps, the swinging foot stepped onto the contralateral foot due to generally small step width. In the remaining steps with separate foot placements, the stance phase could start with forefoot (28%), midfoot (47%), or heel (25%) touchdowns. Despite forefoot or heel initial contacts, the kinematic and loading patterns markedly differed relatively to toe-walking or adult-like two-peaked vertical force profile. Furthermore, while the general stepping parameters (cycle duration, step length, range of motion of proximal joints) were similar, the initial foot contact was consistently associated with specific center-of-pressure excursion, range of motion in the ankle joint, and the center-of-activity of extensor muscles (being shifted by ~5% of cycle toward the end of stance in the "heel" relative to "forefoot" condition). In sum, we found a variety of footfall patterns in conjunction with associated changes in motor patterns. These findings suggest the potential contribution of load-related proprioceptive feedback and/or the expression of variations in the locomotor program already during early manifestations of stepping on ground in human babies.

Planar covariance of upper and lower limb elevation angles during hand-foot crawling in healthy young adults.

Habitual quadrupeds have been shown to display a planar covariance of segment elevation angle waveforms in the fore and hind limbs during many forms of locomotion. The purpose of the current study was to determine if humans generate similar patterns in the upper and lower limbs during hand-foot crawling. Nine healthy young adults performed hand-foot crawling on a treadmill at speeds of 1, 2, and 3 km/h. A principal component analysis (PCA) was applied to the segment elevation angle waveforms for the upper (upper arm, lower arm, and hand) and lower (thigh, shank, and foot) limbs separately. The planarity of the elevation angle waveforms was determined using the sum of the variance explained by the first two PCs and the orientation of the covariance plane was quantified using the direction cosines of the eigenvector orthogonal to the plane, projected upon each of the segmental semi-axes. Results showed that planarity of segment elevation angles was maintained in the upper and lower limbs (explained variance >97%), although a slight decrease was present in the upper limb when crawling at 3 km/h. The orientation of the covariance plane was highly limb-specific, consistent with animal studies and possibly related to the functional neural control differences between the upper and lower limbs. These results may suggest that the motor patterns stored in the central nervous system for quadrupedal locomotion may be retained through evolution and may still be exploited when humans perform such tasks.

Neuromuscular adjustments of gait associated with unstable conditions.

A compact description of coordinated muscle activity is provided by the factorization of electromyographic (EMG) signals. With the use of this approach, it has consistently been shown that multimuscle activity during human locomotion can be accounted for by four to five modules, each one comprised of a basic pattern timed at a different phase of gait cycle and the weighting coefficients of synergistic muscle activations. These modules are flexible, in so far as the timing of patterns and the amplitude of weightings can change as a function of gait speed and mode. Here we consider the adjustments of the locomotor modules related to unstable walking conditions. We compared three different conditions, i.e., locomotion of healthy subjects on slippery ground (SL) and on narrow beam (NB) and of cerebellar ataxic (CA) patients on normal ground. Motor modules were computed from the EMG signals of 12 muscles of the right lower limb using non-negative matrix factorization. The unstable gait of SL, NB, and CA showed significant changes compared with controls in the stride length, stride width, range of angular motion, and trunk oscillations. In most subjects of all three unstable conditions, >70% of the overall variation of EMG waveforms was accounted for by four modules that were characterized by a widening of muscle activity patterns. This suggests that the nervous system adopts the strategy of prolonging the duration of basic muscle activity patterns to cope with unstable conditions resulting from either slippery ground, reduced support surface, or pathology.

Locomotor patterns in cerebellar ataxia.

Several studies have demonstrated how cerebellar ataxia (CA) affects gait, resulting in deficits in multijoint coordination and stability. Nevertheless, how lesions of cerebellum influence the locomotor muscle pattern generation is still unclear. To better understand the effects of CA on locomotor output, here we investigated the idiosyncratic features of the spatiotemporal structure of leg muscle activity and impairments in the biomechanics of CA gait. To this end, we recorded the electromyographic (EMG) activity of 12 unilateral lower limb muscles and analyzed kinematic and kinetic parameters of 19 ataxic patients and 20 age-matched healthy subjects during overground walking. Neuromuscular control of gait in CA was characterized by a considerable widening of EMG bursts and significant temporal shifts in the center of activity due to overall enhanced muscle activation between late swing and mid-stance. Patients also demonstrated significant changes in the intersegmental coordination, an abnormal transient in the vertical ground reaction force and instability of limb loading at heel strike. The observed abnormalities in EMG patterns and foot loading correlated with the severity of pathology [International Cooperative Ataxia Rating Scale (ICARS), a clinical ataxia scale] and the changes in the biomechanical output. The findings provide new insights into the physiological role of cerebellum in optimizing the duration of muscle activity bursts and the control of appropriate foot loading during locomotion.

Visual control of trunk translation and orientation during locomotion.

Previous studies have suggested distinct control of gait characteristics in the anterior-posterior (AP) and medial-lateral (ML) directions in response to visual input. Responses were larger to a ML visual stimulus, suggesting that vision plays a larger role in stabilizing gait in the ML direction. Here, we investigated responses of the trunk during locomotion to determine whether a similar direction dependence is observed. We hypothesized that translation of the trunk would show a similar ML dependence on vision, but that angular deviations of the trunk would show equivalent responses in all directions. Subjects stood or walked on a treadmill at 5 km/h while viewing a virtual wall of white triangles that moved in either the AP or ML direction according to a broadband input stimulus. Frequency response functions between the visual scene motion and trunk kinematics revealed that trunk translation gain was larger across all frequencies during walking compared with standing. Trunk orientation responses were not different from standing at very low frequencies; however, at high frequencies, trunk orientation gain was much higher during walking. Larger gains in response to ML visual scene motion were found for all trunk movements. Higher gains in the ML direction while walking suggest that visual feedback may contribute more to the stability of trunk movements in the ML direction. Vision modified trunk movement behavior on both a slow (translation) and fast (orientation) time scale suggesting a priority for minimizing angular deviations of the trunk. Overall, trunk responses to visual input were consistent with the theme that control of locomotion requires higher-level sensory input to maintain stability in the ML direction.

Muscle activation patterns are bilaterally linked during split-belt treadmill walking in humans.

There is growing evidence that human locomotion is controlled by flexibly combining a set of basic muscle activity patterns. To explore how these patterns are modified to cope with environmental constraints, 10 healthy young adults 1st walked on a split-belt treadmill at symmetric speeds of 4 and 6 km/h for 2 min. An asymmetric condition was then performed for 10 min in which treadmill speeds for the dominant (fast) and nondominant (slow) sides were 6 and 4 km/h, respectively. This was immediately followed by a symmetric speed condition of 4 km/h for 5 min. Gait kinematics and ground reaction forces were recorded. Electromyography (EMG) was collected from 12 lower limb muscles on each side of the body. Nonnegative matrix factorization was applied to the EMG signals bilaterally and unilaterally to obtain basic activation patterns. A cross-correlation analysis was then used to quantify temporal changes in the activation patterns. During the early (1st 10 strides) and late (final 10 strides) phases of the asymmetric condition, the patterns related to ankle plantar flexor (push-off) of the fast limb and quadriceps muscle (contralateral heel contact) of the slow limb occurred earlier in the gait cycle compared with the symmetric conditions. Moreover, a bilateral temporal alignment of basic patterns between limbs was still maintained in the split-belt condition since a similar shift was observed in the unilateral patterns. The results suggest that the temporal structure of these locomotor patterns is shaped by sensory feedback and that the patterns are bilaterally linked.

Plasticity and modular control of locomotor patterns in neurological disorders with motor deficits.

Human locomotor movements exhibit considerable variability and are highly complex in terms of both neural activation and biomechanical output. The building blocks with which the central nervous system constructs these motor patterns can be preserved in patients with various sensory-motor disorders. In particular, several studies highlighted a modular burst-like organization of the muscle activity. Here we review and discuss this issue with a particular emphasis on the various examples of adaptation of locomotor patterns in patients (with large fiber neuropathy, amputees, stroke and spinal cord injury). The results highlight plasticity and different solutions to reorganize muscle patterns in both peripheral and central nervous system lesions. The findings are discussed in a general context of compensatory gait mechanisms, spatiotemporal architecture and modularity of the locomotor program.