Antonino Casabona

Differences in H-reflex between athletes trained for explosive contractions and non-trained subjects

SummaryThe efficacy of type la synapse on alpha-motoneurons of soleus and lateral gastrocnemius muscles has been investigated, using the H-reflex technique, in athletes engaged in sports requiring very rapid and intense contractions (sprinters and volley-ball players) as well as in non-trained subjects. It has been observed, in both muscles, that the ratio between the mean value of the maximal reflex response (Hmax) and the mean value of the maximal direct response (Mmax) elicited upon electrical stimulation of the tibial nerve is significantly smaller in athletes trained for explosive-type movements than in non-trained subjects. This difference in the Hmax:Mmax ratio was dependent on a smaller amplitude of Hmax and not on a greater amplitude of Mmax. No significant differences were observed between sprinters and volley-ball players. In both trained and non-trained subjects, soleus and lateral gastrocnemius muscles displayed significant differences in Hmax: Mmax ratio and Mmax amplitude but not in Hmax amplitude. Since the H-response is considered to be due mainly to activation of the smallest motoneurons in the motoneuronal pools, the difference in Hmax amplitude and Hmax:Mmax ratio between athletes and non-trained subjects could have been dependent on a lower incidence of these motoneurons in the athletes. This is in accord with the mechanical needs of muscles during explosive-type power training. Although this difference ,ay have been wholly determined genetically, the possibility is discussed as to whether the lower incidence in sprinters and volley-ball players of small motoneurons could have been related to a training-induced transformation of small and slow motoneurons into large and fast ones.

Neuromuscular junction disassembly and muscle fatigue in mice lacking neurotrophin-4.

Neurotrophin-4 (NT-4) is produced by slow muscle fibers in an activity-dependent manner and promotes growth and remodeling of adult motorneuron innervation. However, both muscle fibers and motor neurons express NT-4 receptors, suggesting bidirectional NT-4 signaling at the neuromuscular junction. Mice lacking NT-4 displayed enlarged and fragmented neuromuscular junctions with disassembled postsynaptic acetylcholine receptor (AChR) clusters, reduced AChR binding, and acetylcholinesterase activity. Electromyographic responses, posttetanic potentiation, and action potential amplitude were also significantly reduced in muscle fibers from NT-4 knock-out mice. Slow-twitch soleus muscles from these mice fatigued twice as rapidly as those from wild-type mice during repeated tetanic stimulation. Thus, muscle-derived NT-4 is required for maintenance of postsynaptic AChR regions, normal muscular electrophysiological responses, and resistance to muscle fatigue. This neurotrophin may therefore be a key component of an activity-dependent feedback mechanism regulating maintenance of neuromuscular connections and muscular performance.

Synaptic plasticity modulates the spontaneous recovery of locomotion after spinal cord hemisection

Several evidences have demonstrated that adult mammals could achieve a wide range of spontaneous sensory-motor recovery after spinal cord injury by means of various forms of neuroplasticity. In this study we evaluated the possibility that after low-thoracic spinal cord hemisection in the adult rat, significant hindlimb locomotor recovery could occur, and that this recovery may be driven, at least in part, by mechanisms of synaptic plasticity. In order to address these issues, we measured the expression levels of synapsin-I and brain-derived neurotrophic factor by Western blotting, at various time points after hemisection and correlated them with the motor performance on a grid walk test. Regression analysis showed that the expression of synapsin-I was strongly correlated with the spontaneous recovery of hindlimb locomotion (R=0.78). Conversely, neither the expression levels of synapsin-I nor the locomotor recovery were associated with the expression of brain-derived neurotrophic factor. Overall results indicate that after spinal cord hemisection, substantial recovery of hindlimb locomotion could occur spontaneously, and that synaptic plasticity within spinal circuitries below the level of the lesion, could be an important mechanism involved in these processes.

Levels of brain-derived neurotrophic factor and neurotrophin-4 in lumbar motoneurons after low-thoracic spinal cord hemisection.

Neuroplasticity represents a common phenomenon after spinal cord (SC) injury or deafferentation that compensates for the loss of modulatory inputs to the cord. Neurotrophins play a crucial role in cell survival and anatomical reorganization of damaged spinal cord, and are known to exert an activity-dependent modulation of neuroplasticity. Little is known about their role in the earliest plastic events, probably involving synaptic plasticity, which are responsible for the rapid recovery of hindlimb motility after hemisection, in the rat. In order to gain further insight, we evaluated the changes in BDNF and NT-4 expression by lumbar motoneurons after low-thoracic spinal cord hemisection. Early after lesion (30 min), the immunostaining density within lumbar motoneurons decreased markedly on both ipsilateral and contralateral sides of the spinal cord. This reduction was statistically significant and was then followed by a significant recovery along the experimental period (14 days), during which a substantial recovery of hindlimb motility was observed. Our data indicate that BDNF and NT-4 expression could be modulated by activity of spinal circuitry and further support putative involvement of the endogenous neurotrophins in mechanisms of spinal neuroplasticity.

The pendulum test as a tool to evaluate passive knee stiffness and viscosity of patients with rheumatoid arthritis

BackgroundThe pendulum test of Wartenberg is a technique commonly used to measure passive knee motion with the aim to assess spasticity. We used this test to evaluate changes of the knee angular displacement, passive stiffness and viscosity in rheumatoid arthritis patients. Stiffness and viscosity represent passive resistances to joint motion associated with the structural properties of the joint tissue and of the muscular-tendon complex. Stiffness can be considered an intrinsic property of the tissues to resist deformation, while viscosity is related to cohesive forces between adjacent layers of tissues. Both parameters may influence the joint range of motion affecting angular displacement.MethodsNine women with rheumatoid arthritis were compared with a group of healthy women. With the subject half-lying, the relaxed knee was dropped from near-full extension and the characteristics of the ensuring damped unsustained knee oscillation evaluated. The kinematics of leg oscillations was recorded using ultrasonic markers (Zebris CMS HS 10) and the kinetic data were calculated from kinematic and anthropometric measures.ResultsKnee stiffness significantly increased (p < 0.001) in patients with respect to the control group, while differences in viscosity were not significant. Moreover, the amplitudes of first knee flexion (the maximal flexion excursion after knee release) and first knee extension (the maximal extension excursion after the first knee flexion) were significantly decreased (p < 0.001). A regression analysis showed that disease severity correlated moderately with stiffness (R2 = 0.68) and first flexion (R2 = 0.78). Using a multivariate regression, we found that increasing stiffness was the main factor for the reduction of flexion and extension motions.ConclusionWe showed that the Wartenberg test can be considered a practical tool to measure mechanical changes of knee caused by rheumatoid arthritis. This novel application of Wartenberg test could be useful to follow up the effects of pharmacological and rehabilitative interventions in this disease.

Cerebellar encoding of limb position

In this paper, we review single and multijoint studies that, over the years, have provided insight on the cerebellar encoding of limb spatial position. In particular, we present support to the idea that the cerebellum integrates signals from multiple sources to encode global limb parameters. Then, we highlight the result of recent studies that analyzed quantitatively the relationships between limb endpoint position and cerebellar activity. These findings suggest that the cerebellum may share with other central sensorymotor structures an anisotropic representation of limb position characterized by a strong bias along the anteroposterior axis. Finally, we speculate that this anisotropy may also subtend an internal representation of limb mechanics.

Processing of Limb Kinematics in the Interpositus Nucleus

Neural representations of limb movement kinematic parameters are common among central nervous system structures involved in motor control, such as the interpositus nucleus of the cerebellum. Much experimental evidence indicates that neurons in the interpositus may encode limb kinematic parameters both during active, voluntary actions and during limb motion imposed passively, which entrains only sensory afferents. With respect to the sensory processing of information related to movement kinematics, we show that interpositus neuronal activity can parse out the directional from the scalar component (i.e., the movement speed) of the velocity vector. Moreover, a differential role for the anterior and posterior portion of interpositus in encoding these parameters emerged from these data, since the activity of the posterior interpositus was specifically associated to changes of movement speed. Limb movement representations in the interpositus nucleus may be instrumental for the control of goal-directed movements such as shaping hand during grasping or precise foot placement during gait. Finally, we discuss the idea that sensory information about the movement kinematics contribute to both feedback and anticipatory processes for limb movement control.

ALS dysphagia pathophysiology Differential botulinum toxin response

Objectives: This study looked at the effect of botulinum toxin type A (BoTox-A) in patients with amyotrophic lateral sclerosis (ALS) with dysphagia due to isolated upper motor neuron (UMN) involvement or combined UMN/lower motor neuron (LMN) impairment associated with oral phase or oropharyngeal muscles involvement. Establishing whether different pathophysiologic mechanisms underlie different responses to BoTox-A treatment may have important implications for patient management. Patients and methods: We screened 35 patients with sporadic ALS with dysphagia and included in the study 20 out of 35 with upper esophageal sphincter (UES) hyperactivity. We divided these 20 patients into 2 groups, based on the presence or absence of LMN impairment. Irrespective of the groups, we treated all 20 patients with BoTox-A injected into the UES. The study outcome was dysphagia severity scored using the Penetration/Aspiration Scale (PAS), measured before and 2, 4, and 20 weeks after injection. Results: Significant mean PAS reduction was noted at weeks 2 and 4. The botulinum-dependent PAS reduction was entirely associated with the variability shown by the group of patients with no sign of LMN impairment (group 2) and was not observed in group 1. Conclusions: The significant improvement observed in patients with isolated UES dysfunction suggests that a different pathophysiology of ALS dysphagia predisposes patients to a different response to treatment with BoTox-A. This treatment may represent an alternative treatment to percutaneous endoscopic gastrostomy (PEG) or prolong PEG-free time. Classification of evidence: This study provides Class III evidence that botulinum is more effective at 2 and 4 weeks in improving dysphagia in patients with ALS with UES hyperactivity without LMN involvement (vs those with LMN involvement).

Anisotropic representation of forelimb position in the cerebellar cortex and nucleus interpositus of the rat

The relationship between the spatial location of limb and the activity of cerebellar neurons has received little attention and its nature still remains ambiguous. To address this question we studied the activity of Purkinje and nucleus interpositus cells in relation to the spatial location of rat forelimb. A computer-controlled robot arm displaced the limb passively across 15 positions distributed on a parasagittal plane. The limb was upheld for 8 s in each position, which was identified by the Cartesian coordinates of the forepaw. We selected the neurons whose activities were significantly modulated by forepaw position and found that the majority represented preferentially one spatial dimension of the Cartesian plane both in the cerebellar cortex and nucleus interpositus. In particular, the antero-posterior axis was best represented in cerebellar neuronal discharges. This result suggests that the intermediate part of the cerebellum might encode limb position by way of an anisotropic representation of the spatial coordinates of the limb end-point.

On the relation of rat's external cuneate activity to global parameters of forelimb posture.

Using anesthetized adult rats, we studied the relationships between the activity of cells belonging to the external cuneate nucleus (ECN) and passive forelimb positions. In essence, we sought to distinguish between a representation of limb position based on local limb parameters (individual joint angles, for example) or a representation based on more global parameters such as the length and the orientation of the limb axis. Using multivariate regression analyses we found that most neurons showed strong linear relationships with the length and the orientation of the limb axis. Relationships to individual joint angles were, instead, rather weak and in most cases not significant. This result implies an extensive integration of sensory information at the level of second order sensory neurons.