10:40   Neurophysiology 1: Motor Control
Chair: Herman van der Kooij
10:40
15 mins
DYSTONIA EXPLAINED BY ABERRANT PROPRIOCEPTIVE REFLEXES – A MODELING STUDY
Winfred Mugge, Alexander Munts, Alfred Schouten, Frans van der Helm
Abstract: Dystonia is a motor disorder which may develop in neural disorders like Complex Regional Pain Syndrome (CRPS) and entails sustained muscle contractions that result in abnormal postures. It is often hypothesized that a lack of inhibition results in hyperreflexia (exaggerated reflexes), effectively causing dystonia [1]. Humans control their movements using proprioceptive feedback from muscle afferents: muscle force by Golgi tendon organs and muscle stretch by muscle spindles. To assess whether proprioceptive reflexes can explain the features of dystonia a neuromusculoskeletal model was developed. The model describes the human wrist joint with an antagonistic muscle pair [2] and proprioceptive reflexes originating from Ia, II and Ib afferents: muscle stretch, stretch velocity and force. Various scenarios were tested and the results were rated to criteria based on characteristic features of dystonia: abnormal posture, sustained muscle contraction, increased stiffness, worsening with activity and loss of voluntary control. The following reflex scenarios were investigated: 1) no reflexes; 2) normal reflexes; 3) hyperreflexia; 4) imbalanced output, i.e. increased reflex output to only one of the antagonists; and 5) imbalanced sensitivity, i.e. increased reflex sensitivity in only one of the antagonists. With hyperreflexia, the model shows that despite distinct motor dysfunction, none of the reflex pathways can fully account for dystonia, since none of them result in an abnormal posture. The imbalance in the other two scenarios was introduced to provoke an abnormal posture. Although biased imbalance does result in an abnormal posture, again it cannot fully account for dystonia, since other criteria are no longer satisfied. Nevertheless, strength imbalance closely resembles the features of dystonia: effectively satisfying all criteria. In conclusion dystonia may be explained by an imbalance in excitatory muscle force feedback. The other reflex pathways did not satisfy the criteria for dystonia, but based on the oscillatory characteristics may explain features in clonus, tremor, etc. This study shows that dystonia may be explained by proprioceptive reflexes, however it does not rule out other candidates like hyperactive pain withdrawal reflexes. More research is needed to elucidate the cause of dystonia.
10:55
15 mins
THE EFFECT OF NEUROPLASTICITY ON SPINAL REFLEXES, A MODELING STUDY
Jasper Schuurmans, Alfred Schouten, Frans van der Helm
Abstract: Reflexive feedback from muscle afferents has an important contribution to limb stiffness. It has been found that in humans reflex strength varies between tasks and conditions. Pre-synaptic inhibition is a main mechanism of altering the reflex strength. On a longer time scale also neuroplasticity acts on the synaptic connections in the spinal cord, effectively influencing the reflex strength [1]. Hyperreflexia, an increased reflex strength, has been suggested as a mechanism of movement disorders like tonic dystonia [2,3]. Increased reflex gain is thought to be initiated by maladaptive plasticity. The aim of this modeling study was to determine the sensitivity of the mechanical behavior of the neuromusculoskeletal system to changes in spike timing dependent plasticity. The model consisted of a one degree of a freedom limb which was actuated by an antagonistic pair of muscles. The muscles were controlled by a spinal network including two populations of 169 motoneurons and two populations of 196 spinal group Ia interneurons. Muscle spindles provided afferent feedback to the network. Mechanical behavior was assessed by perturbing the limb with a random disturbance force. To effectively counteract the disturbances high limb stiffness would be preferable. The synaptic weights in the network were subject to a spike timing dependent learning rule with a learning window that decayed exponentially with the relative timing between pre-synaptic and postsynaptic spikes. In the sensitivity analysis, systematic variations were made to the magnitudes and time constants of the learning window. The effects on the steady state synaptic weights, muscle activation and limb stiffness were determined. The synaptic connections in the network converged to a steady state when changes to the learning window were symmetric with respect to the two half-planes of potentiation and depression. As long as the areas under the two halves of the learning window were equal, asymmetries between potentiation and depression did not affect convergence of the synaptic strengths. Small asymmetries in the order of 5% between the areas under the half-planes of the learning window caused the synaptic weights not to converge, but to saturate either at zero strength or the maximum synaptic weight allowed. The results suggest that spinal plasticity can have a substantial effect on reflex gains and that convergence critically relies on the ratio between potentiation and depression in a STDP rule.
11:10
15 mins
MICRONEUROGRAPHY IN HUMANS; TWO RESEARCH APPLICATIONS
Leonard van Schelven, Herman van der Kooij, Frans van der Helm, P. Liam Oey
Abstract: In microneurographic (MNG) examinations in humans, a needle electrode is inserted in a peripheral nerve bundle. This direct measurement of nerve signals is not used much, but provides unique information. At the department of Clinical Neurophysiology of the UMC Utrecht, this method has been used in scientific research applications since 1994. We present the method with its technical and safety aspects, and two applications in research of blood pressure regulation and muscle reflexes. A hard part of MNG is the positioning of the electrode. This requires minute electrode manipulations, under constant monitoring of the MNG signal. Suitable electrode positions may be lost even by small movements of the subject or patient, limiting the available measurement time. The durations of searching and measurement depend on the MNG technique used. MNG is applied in research of blood pressure regulation to measure Muscle Sympathetic Nerve Activity (MSNA). MSNA is related to the contraction of muscular veins, which increases the peripheral venous resistance and thereby blood pressure. Measurement of MSNA provides direct information about the activity of the fast blood pressure control system, the baroreflex. The research presented here [1] used MNG to show that the sensitivity of the MSNA baroreflex changed during infusions that affected blood pressure. MNG is also applied in research of muscle reflexes, to give information on the functioning of the muscle spindles. These mechanoreceptors in the muscles signal a combination of muscle stretch and velocity. Their output is used, among others, in spinal muscle reflexes. Their sensitivity can be dynamically adapted by efferent fibres innervating the muscle spindles. Muscle reflexes show complicated non linear behaviour, e.g. it is known that humans can adapt their reflexes to the task performed. MNG can be used to shed light on the role of muscle spindles in this behaviour. We present results of MNG measurements in 7 subjects during passive movements, showing a good ratio of measurement to searching durations. Signal-to-noise ratio and reproducibility proved sufficient to measure changes in the movement sensitivity of human muscle spindles. REFERENCES [1] L. J. van Schelven, J. M. Karemaker, P. J. Blankestijn, and P. L. Oey. Short-term sympathetic baroreflex sensitivity increases at lower blood pressures. Clin.Neurophysiol 119 (4):869-879, 2008.
11:25
15 mins
UNDERSTANDING NEUROMECHANICS IN POST-STROKE RECOVERY: THE EXPLICIT-STROKE PROGRAM
Asbjorn Klomp, Hanneke van der Krogt, Carel Meskers, Jurriaan de Groot, Erwin de Vlugt, Gert Kwakkel, Hans Arendzen, Frans van der Helm
Abstract: Post-stroke movement disorders are dictated by both neuronal and mechanical factors, i.e. altered spinal reflex loop and changed tendomuscular (biomechanical) properties. Previous research revealed dominance of paresis, enhanced mechanical stability and maladaptation of reflexes under active conditions, in contrast to high joint stiffness and hyperreflexia which are found under passive conditions1,2,3. In a recently started multicenter research project, neuromechanics are systematically assessed in patients with (sub-)acute stroke. The ZON-MW funded EXPLICIT-stroke (Explaining PLastICITy after stroke) program4 aims to quantify the changes that represent the functional recovery of arm and hand dexterity after stroke, through an extended program of 2 randomized controlled trials and several longitudinal and cross-sectional studies. Within this program we aim to quantify neuromechanics in relation to observed dynamics in cortical activation as determined by fMRI; corticospinal integrity by TMS; and functional performance measured by clinimetrics and kinematics. Furthermore, the impact of early applied intensive rehabilitation is investigated. The main hypothesis is that loss of corticospinal tract integrity, persistent CNS reorganization and functional impairment is directly related to the absence of reflex modulation. Thirty stroke patients with and thirty without voluntary extension of the wrist and fingers are included and subsequently measured in week 1, 2, 3, 4, 5, 8, 12 and 26 after stroke-onset. Measurements are performed using a high performance, force controlled haptic wrist manipulator (Wristalyzer®, MOOG FCS). A measurement protocol is developed consisting of force and position perturbations at various velocities and angular deviations to assess mechanical and neuronal parameters, e.g. passive and active tendomuscular stiffness, reflex loop time delay, reflex loop gain and reflex loop gain modulation. The data processing is based on linear system identification techniques, to be expanded to nonlinear techniques. It is essential to establish the role of neuromechanical factors in post-stroke recovery to understand the characteristics of stroke related movement disorders. The application of high performance force controlled haptic manipulators in combination with dedicated measurement protocols and advanced system identification allows for an accurate integrated assessment of neuromechanics during natural task performance. A more comprehensive understanding of post-stroke recovery will lead to more customized rehabilitation options for post-stroke movement disorders. REFERENCES [1] Van der Helm FC, Schouten AC, de Vlugt E, Brouwn GG. Identification of intrinsic and reflexive components of human arm dynamics during postural control. J Neurosci Methods. 2002 Sep 15;119(1):1-14. [2] De Vlugt E, Schouten AC, van der Helm FC. Adaptation of reflexive feedback during arm posture to different environments. Biol Cybern. 2002 Jul;87(1):10-26. [3] Meskers CGM, Schouten AC, De Groot JH, Van der Helm FCT, Arendzen JH. Reduced stiffness and reflex gains around the wrist in spasticity after stroke. J Neurorehabil Neural Repair 2006; 20(s):100. [4] Kwakkel G. et al. Impact of early applied upper limb stimulation: The EXPLICIT-stroke programme design. Submitted
11:40
15 mins
NEURAL CONTROL OF RHYTHMIC TAPPING
Alistair Vardy, Andreas Daffertshofer, Peter Beek
Abstract: Rhythmic movements require proper timing. Tapping sequences have proven fruitful for investigating interval timing and were here used to study the underlying central ‘neural clocks’. The variation of inter-tap intervals (ITIs) are typically separated into the variation caused by that central clock and variations caused by an additional motor delay, i.e. a lag between motor command in, e.g., M1 and the observed movement execution [1]. That decomposition implies a negative correlation between consecutive ITIs even for uncorrelated clock events and in the absence of any feedback. This correlation has found support by numerous behavioral studies. Adding an intentional drift to the sequence challenged performance by far as revealed in stronger though more variable activity in the neural timers. Despite this increased challenge, behavioral data suggested that a decomposition of the total variance into a clock and motor delay component remained valid [2], rendering its generality likely. To confirm that the variation in ITI can indeed be properly decomposed clock and motor variance one may determine the temporal correlations of the clock’s underlying activity, which in practice requires detailed information of M1 activity accompanying each individual tap event. Due to the poor signal-to-noise ratio of encephalographic signals, this is not a trivial matter. Template matching supported by spectral analysis may provide a means to define events in single trials. With this idea in mind we used MEG to investigate brain activity accompanying the interval timing of finger tapping and asked which movement-related sources do display temporal correlations comparable to that of the ITI-sequences, and which ones do not. Neural areas whose temporal correlation does not resemble that of the movement do not simply match motor output and/or sensory input, but are likely to characterize the neural timing process, at least if their temporal sequence appears uncorrelated. Sources were determined using synthetic aperture magnetometry. Various motor areas (bilateral M1, PM1, and SMA) were differentially activated and reflected different timing patterns and/or ‘clocking’ mechanisms. The project is financially supported by the Dutch Foundation for Scientific Research (NWO, grant #452-04-344). REFERENCES [1] A.M. Wing, A.B. Kristofferson. “The timing of interresponse intervals”. Percept. Psychophys., Vol. 13, pp. 455-460, (1973). [2] A.N. Vardy, A.Daffertshofer and P.J. Beek, “Tapping with intentional drift”, Exp. Brain. Res., DOI 10.1007/s00221-008-1576-5, (2008).