Characterizing changes in the excitability of corticospinal projections to proximal muscles of the upper limb

Background: There has been an explosion of interest in methods of exogenous brain stimulation that induce changes in the excitability of human cerebral cortex. The expectation is that these methods may promote recovery of function following brain injury. To assess their effects on motor output, it is typical to assess the state of corticospinal projections from primary motor cortex to muscles of the hand, via electromyographic responses to transcranial magnetic stimulation. If a range of stimulation intensities is employed, the recruitment curves (RCs) obtained can, at least for intrinsic hand muscles, be fitted by a sigmoid function.

Objective/hypothesis: To establish whether sigmoid fits provide a reliable basis upon which to characterize the input–output properties of the corticospinal pathway for muscles proximal to the hand, and to assess as an alternative the area under the (recruitment) curve (AURC).

Methods: A comparison of the reliability of these measures, using RCs obtained for muscles that are frequently the targets of rehabilitation.

Results: The AURC is an extremely reliable measure of the state of corticospinal projections to hand and forearm muscles, which has both face and concurrent validity. Construct validity is demonstrated by detection of widely distributed (across muscles) changes in corticospinal excitability induced by paired associative stimulation (PAS).

Conclusion(s): The parameters derived from sigmoid fits are unlikely to provide an adequate means to assess the effectiveness of therapeutic regimes. The AURC can be employed to characterize corticospinal projections to a range of muscles, and gauge the efficacy of longitudinal interventions in clinical rehabilitation.

Investigation of physiological properties of nerves and muscles using electromyography.

The measurement and representation of the electrical activity of muscles [electromyography (EMG)] have a long history from the Victorian Era until today. Currently, EMG has uses both as a research tool, in noninvasively recording muscle activation, and clinically in the diagnosis and assessment of nerve and muscle disease and injury as well as in assessing the recovery of neuromuscular function after nerve damage. In the present report, we describe the use of a basic EMG setup in our teaching laboratories to demonstrate some of these current applications. Our practical also illustrates some fundamental physiological and structural properties of nerves and muscles. Learning activities include 1) displaying the recruitment of muscle fibers with increasing force development; 2) the measurement of conduction velocity of motor nerves; 3) the assessment of reflex delay and demonstration of Jendrassik's maneuver; and 4) a Hoffman reflex experiment that illustrates the composition of mixed nerves and the differential excitability thresholds of fibers within the same nerve, thus aiding an understanding of the reflex nature of muscle control. We can set up the classes at various levels of inquiry depending on the needs/professional requirements of the class. The results can then provide an ideal platform for a discovery learning session/tutorial on how the central nervous system controls muscles, giving insights on how supraspinal control interacts with reflexes to give smooth, precise muscular activation.

Mechanisms of Disease: specialized interstitial cells of the urinary tract--an assessment of current knowledge.

Scientists interested in the smooth muscles of the urinary tract, and their control, have recently been studying cells in the interstitium of tissues that express the c-kit antigen (Kit(+) cells). These cells have morphologic features that are reminiscent of the well-described pacemaker cells in the gut, the interstitial cells of Cajal (ICC). The spontaneous contractile behavior of muscles in the urinary tract varies widely, and it is clear that urinary tract Kit(+) interstitial cells cannot be playing an identical role to that played by the ICC in the gut. Nevertheless, there is increasing evidence that they do play a role in modulating the contractile behavior of adjacent smooth muscle, and might also be involved in mediating neural control. This review outlines the properties of ICC in the gut, and gives an account of the discovery of cells in the interstitium of the main components of the urinary tract. The physiologic properties of such cells and the functional implications of their presence are discussed, with particular reference to the bladder. In this organ, Kit(+) cells are found under the lamina propria, where they might interact with the urothelium and with sensory nerves, and also between and within the smooth-muscle bundles. Confocal microscopy and calcium imaging are being used to assess the physiology of ICC and their interactions with smooth muscles. Differences in the numbers of ICC are seen in smooth muscle specimens obtained from patients with various pathologies; in particular, bladder overactivity is associated with increased numbers of these cells.

Muscle-specific variations in use-dependent crossed-facilitation of corticospinal pathways mediated by transcranial direct current (DC) stimulation

The tendency for contractions of muscles in the upper limb to give rise to increases in the excitability of corticospinal projections to the homologous muscles of the opposite limb is well known. Although the suppression of this tendency is integral to tasks of daily living, its exploitation may prove to be critical in the rehabilitation of acquired hemiplegias. Transcranial direct current (DC) stimulation induces changes in cortical excitability that outlast the period of application. We present evidence that changes in the reactivity of the corticospinal pathway induced by DC stimulation of the motor cortex interact systematically with those brought about by contraction of the muscles of the ipsilateral limb. During the application of flexion torques (up to 50% of maximum) applied at the left wrist, motor evoked potentials (MEPs) were evoked in the quiescent muscles of the right arm by magnetic stimulation of the left motor cortex (M1). The MEPs were obtained prior to and following 10 min of anodal, cathodal or sham DC stimulation of left M1. Cathodal stimulation counteracted increases in the crossed-facilitation of projections to the (right) wrist flexors that otherwise occurred as a result of repeated flexion contractions at the left wrist. In addition, cathodal stimulation markedly decreased the excitability of corticospinal projections to the wrist extensors of the right limb. Thus changes in corticospinal excitability induced by DC stimulation can be shaped (i.e. differentiated by muscle group) by focal contractions of muscles in the limb ipsilateral to the site of stimulation. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Neuromuscular adaptation during skill acquisition on a two degree-of-freedom target-acquisition task: Dynamic movement

In this experiment, we examined the extent to which the spatiotemporal reorganization of muscle synergies mediates skill acquisition on a two degree-of-freedom (df) target-acquisition task. Eight participants completed five practice sessions on consecutive days. During each session they practiced movements to eight target positions presented by a visual display. The movements required combinations of flexion/extension and pronation/supination of the elbow joint complex. During practice sessions, eight targets displaced 5.4 cm from the start position ( representing joint excursions of 54) were presented 16 times. During pre- and posttests, participants acquired the targets at two distances (3.6 cm [36 degrees] and 7.2 cm [72 degrees]). EMG data were recorded from eight muscles contributing to the movements during the pre- and posttests. Most targets were acquired more rapidly after the practice period. Performance improvements were, in most target directions, accompanied by increases in the smoothness of the movement trajectories. When target acquisition required movement in both dfs, there were also practice-related decreases in the extent to which the trajectories deviated from a direct path to the target. The contribution of monofunctional muscles ( those producing torque in a single df) increased with practice during movements in which they acted as agonists. The activity in bifunctional muscles ( those contributing torque in both dfs) remained at pretest levels in most movements. The results suggest that performance gains were mediated primarily by changes in the spatial organization of muscles synergies. These changes were expressed most prominently in terms of the magnitude of activation of the monofunctional muscles.

Visual feedback alters the variations in corticospinal excitability that arise from rhythmic movements of the opposite limb

Augmented visual feedback can have a profound bearing on the stability of bimanual coordination. Indeed, this has been used to render tractable the study of patterns of coordination that cannot otherwise be produced in a stable fashion. In previous investigations (Carson et al. 1999), we have shown that rhythmic movements, brought about by the contraction of muscles on one side of the body, lead to phase-locked changes in the excitability of homologous motor pathways of the opposite limb. The present study was conducted to assess whether these changes are influenced by the presence of visual feedback of the moving limb. Eight participants performed rhythmic flexion-extension movements of the left wrist to the beat of a metronome (1.5 Hz). In 50% of trials, visual feedback of wrist displacement was provided in relation to a target amplitude, defined by the mean movement amplitude generated during the immediately preceding no feedback trial. Motor potentials (MEPs) were evoked in the quiescent muscles of the right limb by magnetic stimulation of the left motor cortex. Consistent with our previous observations, MEP amplitudes were modulated during the movement cycle of the opposite limb. The extent of this modulation was, however, smaller in the presence of visual feedback of the moving limb (FCR omega(2) =0.41; ECR omega(2)=0.29) than in trials in which there was no visual feedback (FCR omega(2)=0.51; ECR omega(2)=0.48). In addition, the relationship between the level of FCR activation and the excitability of the homologous corticospinal pathway of the opposite limb was sensitive to the vision condition; the degree of correlation between the two variables was larger when there was no visual feedback of the moving limb. The results of the present study support the view that increases in the stability of bimanual coordination brought about by augmented feedback may be mediated by changes in the crossed modulation of excitability in homologous motor pathways.

Transfer of resistance training to enhance rapid coordinated force production by older adults

The purpose of this study was to examine the capacity of resistance training to enhance the rapid and coordinated production of force by older people. Thirty adults (greater than or equal to 60 years) completed a visually guided aiming task that required the generation of isometric torque in 2 df about the elbow prior to and following a 4-week training period. Groups of six participants were allocated to two progressive ( 40 - 100% maximal voluntary contraction (MVC)) resistance-training (PRT) groups, to two constant low-load (10% MVC) training groups (CLO) and to one no-training control group. Training movements required the generation of either combined flexion and supination (FLESUP), or combined extension and supination (EXTSUP). In response to training, target acquisition times in the aiming task decreased for all groups; however, both the nature of the training load and the training movement influenced the pattern and magnitude of improvements (EXTSUP_ CLO: 36%, FLESUP_ PRT 26%, EXTSUP_ PRT 22%, FLESUP_ CLO 20%, CONTROL 15%). For one group that trained with progressively increasing loads, there arose a subsequent decrease in performance in one condition of the transfer task. For each group, these adaptations were accompanied by systematic changes in the coordination of muscles about the elbow joint, particularly the biceps brachii.

Resistance training enhances the stability of sensorimotor coordination

Strategics for the control of human movement are constrained by the neuroanatomical characteristics of the motor system. In particular, there is evidence that the capacity of muscles for producing force has a strong influence on the stability of coordination in certain movement tasks. In the present experiment, our aim was to determine whether physiological adaptations that cause relatively long-lasting changes in the ability of muscles to produce force can influence the stability of coordination in a systematic manner. We assessed the effects of resistance training on the performance of a difficult coordination task that required participants to synchronize or syncopate movements of their index finger with an auditory metronome. Our results revealed that training that increased isometric finger strength also enhanced the stability of movement coordination. These changes were accompanied by alterations in muscle recruitment patterns. In Particular, the trained muscles were recruited in a more consistent fashion following the programme of resistance training. These results indicate that resistance training produces functional adaptations of the neuroanatomical constraints that underlie the control of voluntary movement.

Muscle coordination during rapid force production by young and older adults

Background. Older adults typically exhibit dramatic reductions in the rate of force development and deficits in the execution of rapid coordinated movements. The purpose of the current study was to investigate the association between the reduced rate of force development exhibited by older adults and the ability to coordinate groups of muscles.

The effect of simultaneous contractions of ipsilateral muscles on changes in corticospinal excitability induced by paired associative stimulation (PAS)

Consideration was given to means of increasing the reliability and muscle specificity of paired associative stimulation (PAS) by utilising the phenomenon of crossed-facilitation. Eight participants completed three separate sessions: isometric flexor contractions of the left wrist at 20% of maximum voluntary contraction (MVC) simultaneously with PAS (20s intervals; 14 min duration) delivered at the right median nerve and left primary motor cortex (MI); isometric contractions at 20% of MVC: and PAS only ( 14 min). Eight further participants completed two sessions of longer duration PAS (28 min): either alone or in conjunction with flexion contractions of the left wrist. Thirty motor potentials (MEPs) were evoked in the right flexor (rFCR) and extensor (rECR) carpi radialis muscles by magnetic stimulation of left M1 Prior to the interventions, immediately post-intervention, and 10 min post-intervention. Both 14 and 28 min of combined PAS and (left wrist flexion) contractions resulted in reliable increases in rFCR MEP amplitude, which were not present in rECR. In the PAS only conditions, 14 min of stimulation gave rise to unreliable increases in MEP amplitudes in rFCR and rECR, whereas 28 min of PAS induced small (unreliable) changes only for rFCR. These results support the conclusion that changes in the excitability of the corticospinal pathway induced by PAS interact with those associated with contraction of the muscles ipsilateral to the site of cortical stimulation. Furthermore, focal contractions applied by the opposite limb increase the extent and muscle specificity of the induced changes in excitability associated with PAS. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Bradykinin-related peptides (BRPs) from skin secretions of three genera of phyllomedusine leaf frogs and their comparative pharmacological effects on mammalian smooth muscles

While bradykinin has been identified in the skin secretions from several species of amphibian, bradykinin-related peptides (BRPs) are more common constituents. These peptides display a plethora of primary structural variations from the type peptide which include single or multiple amino acid substitutions, N- and/or C-terminal extensions and post-translational modifications such as proline hydroxylation and tyrosine sulfation. Such modified peptides have been reported in species from many families, including Bombinatoridae, Hylidae and Ranidae. The spectrum of these peptides in a given species is thought to be reflective of its predator profile from different vertebrate taxa. Here we report the isolation of BRPs and parallel molecular cloning of their respective biosynthetic precursor-encoding cDNAs from the skin secretions of the Mexican leaf frog (Pachymedusa dacnicolor), the Central American red-eyed leaf frog (Agalychnis callidryas) and the South American orange-legged leaf frog (Phyllomedusa hypochondrialis). Additionally, the eight different BRPs identified were chemically synthesized and screened for bioactivity using four different mammalian smooth muscle preparations and their effects and rank potencies were found to be radically different in these with some acting preferentially through bradykinin B1-type receptors and others through B2-type receptors.

Distribution of terminal nerve entry points to the flexor and extensor groups of forearm muscles:An anatomical study

The motor points of the skeletal muscles, mainly of interest to anatomists and physiologists, have recently attracted much attention from researchers in the field of functional electrical stimulation. The muscle motor point has been defined as the entry point of the motor nerve branch into the epimysium of the muscle belly. Anatomists have pointed out that many muscles in the limbs have multiple motor points. Knowledge of the location of nerve branches and terminal nerve entry points facilitates the exact insertion and the suitable selection of the number of electrodes required for each muscle for functional electrical stimulation. The present work therefore aimed to describe the number, location, and distribution of motor points in the human forearm muscles to obtain optimal hand function in many clinical situations. Twenty three adult human cadaveric forearms were dissected. The numbers of primary nerves and motor points for each muscle were tabulated. The mean numbers and the standard deviation were calculated and grouped in tables. Data analyses were performed with the use of a statistical analysis package (SPSS 13.0). The proximal third of the muscle was the usual part of the muscle that received the motor points. Most of the forearm muscles were innervated from the lateral side and deep surface of the muscle. The information in this study may also be usefully applied in selective denervation procedures to balance muscles in spastic upper limbs. Copyright © 2007 Via Medica.

An anatomical study of the arterial and nerve supply of the infrahyoid muscles

A precise knowledge of the sources of the arterial and neural supply of the sternohyoid (SH), sternothyroid (STM), and superior belly of omohyoid (OM) is of value to surgeons using the infrahyoid muscles in reconstruction procedures of the head and neck. This study was designed to define the anatomical bases of the variable sources of the arterial and neural supply of these muscles. Fourteen cadavers were unilaterally dissected in the neck region, and the arterial pedicles of these muscles were followed and accurate measurements were taken. For the SH, two arterial pedicles (superior and inferior) originated from the superior thyroid artery ST and supplied the muscle in 57.1% of cases. The inferior pedicle was absent in 42.9% of cases. As regards the STM, one arterial pedicle from the ST supplied its upper end by multiple branches in 57.1% of cases. In 14.3% of cases, branches from the inferior thyroid artery (IT) supplied the STM in addition to its supply from the ST. As regards the OM, two arterial pedicles originated from the ST and supplied its upper and lower ends in 57.1% of cases. The main artery from the ST to the superior belly of OM entered at its superior portion. The ansa cervicalis (AC) innervated the infrahyoid muscles. SH usually had a double nerve supply. In 57.1% of cases, its superior part was innervated by the nerve to the superior belly of OM. Its inferior part received branches from the AC. In 35.7% of cases, its superior part received direct branches from the AC. As regards the STM, in (71.4%) of cases, a common trunk arose from the loop and supplied the inferior part of both the SH and STM. The nerve supply to the superior belly of OM originated from the AC below the loop in 64.3% of cases. These data will be useful for preserving the neuro-vascular supply of the infrahyoid muscles during flap preparation.