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.

Training of Reaching in Stroke Survivors With Severe and Chronic Upper Limb Paresis Using a Novel Nonrobotic Device: A Randomized Clinical Trial

Background and Purpose—Severe upper limb paresis is a major contributor to disability after stroke. This study investigated the efficacy of a new nonrobotic training device, the Sensorimotor Active Rehabilitation Training (SMART) Arm, that was used with or without electromyography-triggered electrical stimulation of triceps brachii to augment elbow extension, permitting stroke survivors with severe paresis to practice a constrained reaching task.

Methods—A single-blind, randomized clinical trial was conducted with 42 stroke survivors with severe and chronic paresis. Thirty-three participants completed the study, of whom 10 received training using the SMART Arm with electromyography-triggered electrical stimulation, 13 received training using the SMART Arm alone, and 10 received no intervention (control). Training consisted of 12 1-hour sessions over 4 weeks. The primary outcome measure was “upper arm function,” item 6 of the Motor Assessment Scale. Secondary outcome measures included impairment measures; triceps muscle strength, reaching force, modified Ashworth scale; and activity measures: reaching distance and Motor Assessment Scale. Assessments were administered before (0 weeks) and after training (4 weeks) and at 2 months follow-up (12 weeks).

Results—Both SMART Arm groups demonstrated significant improvements in all impairment and activity measures after training and at follow-up. There was no significant difference between these 2 groups. There was no change in the control group.

Conclusions—Our findings indicate that training of reaching using the SMART Arm can reduce impairment and improve activity in stroke survivors with severe and chronic upper limb paresis, highlighting the benefits of intensive task-oriented practice, even in the context of severe paresis.

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.

Age-related differences in rapid muscle activation after rate of force development training of the elbow flexors

In young adults, improvements in the rate of force development as a result of resistance training are accompanied by increases in neural drive in the very initial phase of muscle activation. The purpose of this experiment was to determine if older adults also exhibit similar adaptations in response to rate of force development (RFD) training. Eight young (21-35 years) and eight older (60-79 years) adults were assessed during the production of maximum rapid contractions, before and after four weeks of progressive resistance training for the elbow flexors. Young and older adults exhibited significant increases (P<0.01) in peak RFD, of 25.6% and 28.6% respectively. For both groups the increase in RFD was accompanied by an increase in the root mean square (RMS) amplitude and in the rate of rise (RER) in the electromyogram (EMG) throughout the initial 100 ms of activation. For older adults, however, this training response was only apparent in the brachialis and brachioradialis muscles. This response was not observed in surface EMG recorded from the biceps brachii muscle during either RFD testing or throughout training, nor was it observed in the pronator teres muscle. The minimal adaptations observed for older adults in the bifunctional muscles biceps brachii and pronator teres are considered to indicate a compromise of the neural adaptations older adults might experience in response to resistance training.

Early alterations in serum creatine kinase and total cholesterol following high intensity eccentric muscle actions

Aim. The purpose of this experiment was to assess the levels of muscle soreness, serum total cholesterol (TC) and creatine kinase (CK) in the first 48 hours following fatiguing eccentric exercise performed with the triceps brachii.

Bimanual coordination: constraints imposed by the relative timing of homologous muscle activation

It has often been supposed that patterns of rhythmic bimanual coordination in which homologous muscles are engaged simultaneously, are performed in a more stable manner than those in which the same muscles are activated in an alternating fashion. In order to assess the efficacy of this constraint, the present study investigated the effect of forearm posture (prone or supine) on bimanual abduction-adduction movements of the wrist in isodirectional and non-isodirectional modes of coordination. Irrespective of forearm posture, non-isodirectional coordination was observed to be more stable than isodirectional coordination. In the latter condition, there was a more severe deterioration of coordination accuracy/stability as a function of cycling frequency than in the former condition. With elevations in cycling frequency, the performers recruited extra mechanical degrees of freedom, principally via flexion-extension of the wrist, which gave rise to increasing motion in the vertical plane. The increases in movement amplitude in the vertical plane were accompanied by decreasing amplitude in the horizontal plane. In agreement with previous studies, the present findings confirm that the relative timing of homologous muscle activation acts as a principal constraint upon the stability of interlimb coordination. Furthermore, it is argued that the use of manipulations of limb posture to investigate the role of other classes of constraint (e.g. perceptual) should be approached with caution because such manipulations affect the mapping between muscle activation patterns, movement dynamics and kinematics.

Phasic modulation of corticomotor excitability during passive movement of the upper limb: effects of movement frequency and muscle specificity

Modulations in the excitability of spinal reflex pathways during passive rhythmic movements of the lower limb have been demonstrated by a number of previous studies [4]. Less emphasis has been placed on the role of supraspinal pathways during passive movement, and on tasks involving the upper limb. In the present study, transcranial magnetic stimulation (TMS) was delivered to subjects while undergoing passive flexion-extension movements of the contralateral wrist. Motor evoked potentials (MEPs) of flexor carpi radialis (FCR) and abductor pollicus brevis (APB) muscles were recorded. Stimuli were delivered in eight phases of the movement cycle during three different frequencies of movement. Evidence of marked modulations in pathway excitability was found in the MEP amplitudes of the FCR muscle, with responses inhibited and facilitated from static values in the extension and flexion phases, respectively. The results indicated that at higher frequencies of movement there was greater modulation in pathway excitability. Paired-pulse TMS (sub-threshold conditioning) at short interstimulus intervals revealed modulations in the extent of inhibition in MEP amplitude at high movement frequencies. In the APE muscle, there was some evidence of phasic modulations of response amplitude, although the effects were less marked than those observed in FCR. It is speculated that these modulatory effects are mediated via Ia afferent pathways and arise as a consequence of the induced forearm muscle shortening and lengthening. Although the level at which this input influences the corticomotoneuronal pathway is difficult to discern, a contribution from cortical regions is suggested. (C) 2001 Published by Elsevier Science B.V.

Changes in muscle recruitment patterns during skill acquisition

The control of movement is predicated upon a system of constraints of musculoskeletal and neural origin. The focus of the present study was upon the manner in which such constraints are adapted or superseded during the acquisition of motor skill. Individuals participated in five experimental sessions, ill which they attempted to produce abduction-adduction movements of the index finger in time with an auditory metronome. During each trial, the metronome frequency was increased in eight steps from an individually determined base frequency. Electromyographic (EMC) activity was recorded from first dorsal interosseous (FDI), first volar interosseous (FVI), flexor digitorum superficialis (FDS), and extensor digitorum communis (EDC) muscles. The movements produced on the final day of acquisition more accurately matched the required profile, and exhibited greater spatial and temporal stability, than those generated during initial performance. Tn the early stages of skill acquisition, an alternating pattern of activation in FDI and FVI was maintained, even at the highest frequencies. Tn contrast, as the frequency of movement was increased, activity in FDS and EDC was either tonic or intermittent. As learning proceeded, alterations in recruitment patterns were expressed primarily in the extrinsic muscles (EDC and FDS). These changes took the form of increases in the postural role of these muscles, shifts to phasic patterns of activation, or selective disengagement of these muscles. These findings suggest that there is considerable flexibility in the composition of muscle synergies, which is exploited by individuals during the acquisition of coordination.

Ca2+-activated Cl- current in retinal arteriolar smooth muscle.

PURPOSE: To characterize the biophysical, pharmacologic, and functional properties of the Ca(2+)-activated Cl(-) current in retinal arteriolar myocytes. METHODS: Whole-cell perforated patch-clamp recordings were made from myocytes within intact isolated arteriolar segments. Arteriolar tone was assessed using pressure myography. RESULTS: Depolarizing of voltage steps to -40 mV and greater activated an L-type Ca(2+) current (I(Ca(L))) that was followed by a sustained current. Large tail currents (I(tail)) were observed on stepping back to -80 mV. The sustained current and I(tail) reversed close to 0 mV in symmetrical Cl(-) concentrations. The ion selectivity sequence for I(tail) was I(-)> Cl(-)> glucuronate. Outward I(tail) was sensitive to the Cl(-) channel blockers 9-anthracene-carboxylic acid (9-AC; 1 mM), 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS; 1 mM), and disodium 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS; 1 mM), but only DIDS produced a substantial (78%) block of inward tail currents at -100 mV. I(tail) was decreased in magnitude when the normal bathing medium was substituted with Ca(2+)-free solution or if I(Ca(L)) was inhibited by 1 microM nimodipine. Caffeine (10 mM) produced large transient currents that reversed close to the Cl(-) equilibrium potential and were blocked by 1 mM DIDS or 100 microM tetracaine. DIDS had no effect on basal vascular tone in pressurized arterioles but dramatically reduced the level of vasoconstriction observed in the presence of 10 nM endothelin-1. CONCLUSIONS: Retinal arteriolar myocytes have I(Cl(Ca)), which may be activated by Ca(2+) entry through L-type Ca(2+) channels or Ca(2+) release from intracellular stores. This current appears to contribute to agonist-induced retinal vasoconstriction.

Testing the reliability of the JEOL FEGSEM 6500F electron microprobe for quantitative major element analysis of glass shards from rhyolitic tephra.

Electronprobe microanalysis is now widely adopted in tephra studies as a technique for determining the major element geochemistry of individual glass shards. Accurate geochemical characterization is crucial for enabling robust tephra-based correlations; such information may also be used to link the tephra to a specific source and often to a particular eruption. In this article, we present major element analyses for rhyolitic natural glass standards analysed on three different microprobes and the new JEOL FEGSEM 6500F microprobe at Queen’s University Belfast. Despite the scatter in some elements, good comparability is demonstrated among data yielded from this new system, the previous Belfast JEOL-733 Superprobe, the JEOL-8200 Superprobe (Copenhagen) and the existing long-established microprobe facility in Edinburgh. Importantly, our results show that major elements analysed using different microprobes and variable operating conditions allow two high-silica glasses to be discriminated accurately.

Deletion of TRPC4 and TRPC6 in Mice Impairs Smooth Muscle Contraction and Intestinal Motility In Vivo.

BACKGROUND & AIMS: Downstream effects of muscarinic receptor stimulation in intestinal smooth muscle include contraction and intestinal transit. We thought to determine whether classic transient receptor potential (TRPC) channels integrate the intracellular signaling cascades evoked by the stimulated receptors and thereby contribute to the control of the membrane potential, Ca-influx, and cell responses. METHODS: We created trpc4-, trpc6-, and trpc4/trpc6-gene-deficient mice and analyzed them for intestinal smooth muscle function in vitro and in vivo. RESULTS: In intestinal smooth muscle cells TRPC4 forms a 55 pS cation channel and underlies more than 80% of the muscarinic receptor-induced cation current (mI(CAT)). The residual mI(CAT) depends on the expression of TRPC6, indicating that TRPC6 and TRPC4 determine mI(CAT) channel activity independent of other channel subunits. In TRPC4-deficient ileal myocytes the carbachol-induced membrane depolarizations are diminished greatly and the atropine-sensitive contraction elicited by acetylcholine release from excitatory motor neurons is reduced greatly. Additional deletion of TRPC6 aggravates these effects. Intestinal transit is slowed down in mice lacking TRPC4 and TRPC6. CONCLUSIONS: In intestinal smooth muscle cells TRPC4 and TRPC6 channels are gated by muscarinic receptors and are responsible for mI(CAT). They couple muscarinic receptors to depolarization of intestinal smooth muscle cells and voltage-activated Ca(2+)-influx and contraction, and thereby accelerate small intestinal motility in vivo.

Bystander-induced differentiation: a major response to targeted irradiation of a urothelial explant model.

A ureter primary explant technique, using porcine tissue sections was developed to study bystander effects under in vivo like conditions where dividing and differentiated cells are present. Targeted irradiations of ureter tissue fragments were performed with the Gray Cancer Institute charged particle microbeam at a single location (2 microm precision) with 10 3He2+ particles (5 MeV; LET 70 keV/microm). After irradiation the ureter tissue section was incubated for 7 days allowing explant outgrowth to be formed. Differentiation was estimated using antibodies to Uroplakin III, a specific marker of terminal urothelial differentiation. Even although only a single region of the tissue section was targeted, thousands of additional cells were found to undergo bystander-induced differentiation in the explant outgrowth. This resulted in an overall increase in the fraction of differentiated cells from 63.5+/-5.4% to 76.6+/-5.6%. These changes are much greater than that observed for the induction of damage in this model. One interpretation of these results is that in the tissue environment, differentiation is a much more significant response to targeted irradiation and potentially a protective mechanism.

Kassina senegalensis skin tachykinins: Molecular cloning of kassinin and (Thr2, Ile9)-kassinin biosynthetic precursor cDNAs and comparative bioactivity of mature tachykinins on the smooth muscle of rat urinary bladder

Tachykinins are among the most widely-studied families of regulatory peptides characterized by a highly-conserved C-terminal -Phe-X-Gly-Leu-Met.amide motif, which also constitutes the essential bioactive core. The amphibian skin has proved to be a rich source of these peptides with physalaemin from the skin of Physalaemus fuscomaculatus representing the archetypal aromatic tachykinin (X = Tyr or Phe) and kassinin from the skin of Kassina senegalensis representing the archetypal aliphatic tachykinin in which X = Val or Ile. Despite the primary structures of both mature peptides having been known for at least 30 years, neither the structures nor organizations of their biosynthetic precursors have been reported. Here we report the structure and organization of the biosynthetic precursor of kassinin deduced from cDNA cloned from a skin secretion library. In addition, a second precursor cDNA encoding the novel kassinin analog (Thr2, Ile9)-kassinin was identified as was the predicted mature peptide in skin secretion. Both transcripts exhibited a high degree of nucleotide sequence similarity and of open-reading frame translated amino acid sequences of putative precursor proteins. The translated preprotachykinins each consisted of 80 amino acid residues encoding single copies of either kassinin or its site-substituted analog. Synthetic replicates of each kassinin were found to be active on rat urinary bladder smooth muscle at nanomolar concentrations. The structural organization of both preprotachykinins differs from that previously reported for those of Odorrana grahami skin indicating a spectrum of diversity akin to that established for amphibian skin preprobradykinins.