Mdx myotubes have normal excitability but show reduced contraction-relaxation dynamics.

The pathogenesis of Duchenne muscular dystrophy (DMD), characterised by lack of the cytoskeletal protein dystrophin, is not completely understood. An early event in the degenerative process of DMD muscle could be a rise in cytosolic calcium concentration. In order to investigate whether this leads to alterations of contractile behaviour, we studied the excitability and contractile properties of cultured myotubes from control (C57BL/10) and mdx mice, an animal model for DMD. The myotubes were stimulated electrically and their motion was recorded photometrically. No significant differences were found between control and mdx myotubes with respect to the following parameters: chronaxy and rheobase (0.33 +/- 0.03 ms and 23 +/- 4 V vs. 0.39 +/- 0.07 ms and 22 +/- 2 V for C57 and mdx myotubes, respectively), tetanisation frequency (a similar distribution pattern was found between 5 and 30 Hz), fatigue during tetanus (found in 35% of both types of myotubes) and post-tetanic contracture. In contrast, contraction and relaxation times were longer (P < 0.005) in mdx (36 +/- 2 and 142 +/- 13 ms, respectively) than in control myotubes (26 +/- 1 and 85 +/- 9 ms, respectively). Together with our earlier findings, these results suggest a decreased capacity for calcium removal in mdx cells leading, in particular, to alterations of muscle relaxation.

Reliability of a new measure of motoneuron excitability

Objectlve:--This study examined the intraclass reliability· of different measures of the excitability of the Hoffmann reflex, derived from stimulus-response curves. The slope of the regression line of the H-reflex stimulus-response curve advocated by Funase et al. (1994) was also compared to the peak of the first derivative of the H-reflex stimulus-response curve (dHIdVmax), a new measure introduced in this investigation. A secondary purpose was to explore the possibility of mood as a covariate when measuring excitability of the H-reflex arc. Methods: The H-reflex amplitude at a stimulus intensity corresponding to 5% of the maximum M-wave (Mmax) is an established measure that was used as an additional basis of comparison. The H-reflex was elicited in the soleus for 24 subjects (12 males and 12 females) on five separate days. Vibration was applied to the Achilles tendon prior to stimulation to test the sensitivity of the measures on test day four. The means of five evoked potentials at each gradually increasing intensity, from below H-reflex threshold to above Mmax, were used to create both the H-reflex and M-wave stimulus response curves for each subject across test days. The mood of the subjects was assessed using the Subjective Exercise Experience Scale (SEES) prior to the stimulation protocol each day. Results: There was a modest decrease in all H-reflex measures from the first to third test day, but it was non-significant (P's>0.05). All measures of the H-reflex exhibited a profound reduction following vibration on test day four, and then returned to baseline levels on test day five (P's<0.05). The intraclass correlation coefficient (ICC) for H-reflex amplitude at 5% of Mmax was 0.85. The ICC for the slope of the regression line was 0.79 while it was 0.89 for dH/dVmax. Maximum M-wave amplitude had an ICC of 0.96 attesting to careful methodological controls. The SEES subscales of fatigue and psychological well-being remained unchanged IV across the five days. The psychological distress subscale (PO.05). Conclusions: The peak of the first derivative of the H-reflex stimulus-response curve (dH/dVmax) was shown to have comparable reliability and sensitivity to other more established measures of excitability. Psychological distress and the amplitude of the H-reflex at 5% Mmax follow similar trends across days, however there was no significant correlation between the two measures. Significance: The proposed method appears to be a more robust measure ofH-reflex excitability than the other methods tested. As such it would be an advantageous method to apply in clinical and investigative settings. Additionally, the results suggest that the relationship between psychological distress and H-reflex amplitude should be investigated further.

Corticospinal excitability not affected by negative motor imagery or intention

Bien que l’imagerie motrice positive ait été bien étudiée et est utilisée en réhabilitation, l’effet de l’imagerie motrice négative est beaucoup moins connu. Le but de cette recherche était de définir si l’intention et/ou l’imagerie motrice négative serait en mesure de réduire l’effet d’une stimulation magnétique transcrânienne (SMT) sur le cortex moteur. Vingt participants ont reçu trente stimulations de SMT dans trois situations différentes : En restant passif, en portant une attention particulière aux sensations dans leur main ou en tentant de réduire l’effet de la SMT. La moitié des participants ont utilisé une stratégie d’imagerie motrice, l’autre moitié leur intention. Dans les deux cas, l’amplitude dans la condition de modulation n’a pas été réduite de façon significative.

Age-related effects of Ginkgo biloba extract on synaptic plasticity and excitability

EGb 761 is a standardized extract from the Ginkgo biloba leaf and is purported to improve age-related memory impairment. The acute and chronic effect of EGb 761 on synaptic transmission and plasticity in hippocampal slices from young adult (8-12 weeks) and aged (18-24 months) C57B1/6 mice was tested because hippocampal plasticity is believed to be a key component of memory. Acutely applied EGb 761 significantly increased neuronal excitability in slices from aged mice by reducing the population spike threshold and increased the early phase of long-term potentiation, though there was no effect in slices from young adults. In chronically treated mice fed for 30 days with an EGb 761-supplemented diet, EGb 761 significantly increased the population spike threshold and long-term potentiation in slices from aged animals, but had no effect on slices from young adults. The rapid effects of EGb 761 on plasticity indicate a direct interaction with the glutamatergic system and raise interesting implications with respect to a mechanism explaining its effect on cognitive enhancement in human subjects experiencing dementia. (C) 2003 Elsevier Inc. All rights reserved.

Coding of visual space during motor preparation: approaching objects rapidly modulate corticospinal excitability in hand-centered coordinates

Defensive behaviors, such as withdrawing your hand to avoid potentially harmful approaching objects, rely on rapid sensorimotor transformations between visual and motor coordinates. We examined the reference frame for coding visual information about objects approaching the hand during motor preparation. Subjects performed a simple visuomanual task while a task-irrelevant distractor ball rapidly approached a location either near to or far from their hand. After the distractor ball appearance, single pulses of transcranial magnetic stimulation were delivered over the subject's primary motor cortex, eliciting motor evoked potentials (MEPs) in their responding hand. MEP amplitude was reduced when the ball approached near the responding hand, both when the hand was on the left and the right of the midline. Strikingly, this suppression occurred very early, at 70-80ms after ball appearance, and was not modified by visual fixation location. Furthermore, it was selective for approaching balls, since static visual distractors did not modulate MEP amplitude. Together with additional behavioral measurements, we provide converging evidence for automatic hand-centered coding of visual space in the human brain.

Phosphorylation of the voltage-gated potassium channel Kv2.1 by AMP-activated protein kinase regulates membrane excitability

Firing of action potentials in excitable cells accelerates ATP turnover. The voltage-gated potassium channel Kv2.1 regulates action potential frequency in central neurons, whereas the ubiquitous cellular energy sensor AMP-activated protein kinase (AMPK) is activated by ATP depletion and protects cells by switching off energy-consuming processes. We show that treatment of HEK293 cells expressing Kv2.1 with the AMPK activator A-769662 caused hyperpolarizing shifts in the current-voltage relationship for channel activation and inactivation. We identified two sites (S440 and S537) directly phosphorylated on Kv2.1 by AMPK and, using phosphospecific antibodies and quantitative mass spectrometry, show that phosphorylation of both sites increased in A-769662-treated cells. Effects of A-769662 were abolished in cells expressing Kv2.1 with S440A but not with S537A substitutions, suggesting that phosphorylation of S440 was responsible for these effects. Identical shifts in voltage gating were observed after introducing into cells, via the patch pipette, recombinant AMPK rendered active but phosphatase-resistant by thiophosphorylation. Ionomycin caused changes in Kv2.1 gating very similar to those caused by A-769662 but acted via a different mechanism involving Kv2.1 dephosphorylation. In cultured rat hippocampal neurons, A-769662 caused hyperpolarizing shifts in voltage gating similar to those in HEK293 cells, effects that were abolished by intracellular dialysis with Kv2.1 antibodies. When active thiophosphorylated AMPK was introduced into cultured neurons via the patch pipette, a progressive, time-dependent decrease in the frequency of evoked action potentials was observed. Our results suggest that activation of AMPK in neurons during conditions of metabolic stress exerts a protective role by reducing neuronal excitability and thus conserving energy.

Effects of action observation on corticospinal excitability: muscle specificity, direction, and timing of the mirror response

Many human behaviours and pathologies have been attributed to the putative mirror neuron system, a neural system that is active during both the observation and execution of actions. While there are now a very large number of papers on the mirror neuron system, variations in the methods and analyses employed by researchers mean that the basic characteristics of the mirror response are not clear. This review focuses on three important aspects of the mirror response, as measured by modulations in corticospinal excitability: (1) muscle specificity, (2) direction, and (3) timing of modulation. We focus mainly on electromyographic (EMG) data gathered following single-pulse transcranial magnetic stimulation (TMS), because this method provides precise information regarding these three aspects of the response. Data from paired-pulse TMS paradigms and peripheral nerve stimulation (PNS) are also considered when we discuss the possible mechanisms underlying the mirror response. In this systematic review of the literature, we examine the findings of 85 TMS and PNS studies of the human mirror response, and consider the limitations and advantages of the different methodological approaches these have adopted in relation to discrepancies between their findings. We conclude by proposing a testable model of how action observation modulates corticospinal excitability in humans. Specifically, we propose that action observation elicits an early, non-specific facilitation of corticospinal excitability (at around 90 ms from action onset), followed by a later modulation of activity specific to the muscles involved in the observed action (from around 200 ms). Testing this model will greatly advance our understanding of the mirror mechanism and provide a more stable grounding on which to base inferences about its role in human behaviour.

Eugenol modifies the excitability of rat sciatic nerve and superior cervical ganglion neurons

Eugenol is a phenylpropene obtained from the essential oils of plants such as clove and basil which has ample use in dentistry. Eugenol possesses analgesic effects that may be related to the inhibition of voltage-dependent Na(+) channels and/or to the activation of TRPV1 receptors or both. In the present study, electrophysiological parameters were taken from the compound action potentials of the isolated rat sciatic nerve and from neurons of the superior cervical ganglion (SCG) impaled with sharp microelectrodes under current-clamp conditions. In the isolated rat sciatic nerve, eugenol inhibited the compound action potential in a concentration-dependent manner. Action potentials recorded from SCG neurons were inhibited by eugenol with an IC(50) of 0.31 mM. At high concentrations (2 mM), during brief applications. eugenol caused significant action potential blockade while it did not interfere with the resting membrane potential or the membrane input resistance. Surprisingly, however, at low eugenol concentrations (0.6 mM), during long time applications, a reversible reduction (by about 50%) in the input membrane resistance was observed, suggesting the possible involvement of a secondary delayed effect of eugenol to reduce neuronal excitability. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Corticomotor excitability during precision motor tasks

The aim of this preliminary study was to investigate motor cortex (cortical) excitability between a similar fine visuomotor task of varying difficulty. Ten healthy adults (three female, seven male; 20–45 years of age) participated in the study. Participants were instructed to perform a fine visuomotor task by statically abducting their first index finger against a force transducer which displayed the level of force (represented as a marker) on a computer monitor. This marker was to be maintained between two stationary bars, also displayed on the computer monitor. The level of difficulty was increased by amplifying the position of the marker, making the task more difficult to control. Cortical measures of motor evoked potential (MEP) and silent period (SP) duration in first dorsal interosseous (FDI) muscle were obtained using transcranial magnetic stimulation (TMS) while the participant maintained the “easy” or “difficult” static task. An 11.8% increase in MEP amplitude was observed when subjects undertook the “difficult” task, but no differences in MEP latency or SP duration. The results from this preliminary study suggest that cortical excitability increases reflect the demand required to perform tasks requiring greater precision with suggestions for further research discussed.

Comparison of corticomotor excitability during visuomotor dynamic and static tasks

The human central nervous system (CNS) has the ability to modulate its activity during the performance of different movements. Recent evidence, however, suggests that the CNS can also modulate its activity in the same movement but with increased precision during a visuomotor static task. This study aimed to extend on these findings by using transcranial magnetic stimulation (TMS) to measure the CNS during the performance of two visuomotor dynamic tasks. Twelve volunteers participated in this study, performing two separate motor tasks. Study I (“Position Tracking”) involved participants to perform a visuomotor tracking task using a dial potentiometer and matching their response icon to the computer generated tracking icon whilst holding a pincer grip. Study II (“Force Tracking”) involved participants to perform a similar visuomotor tracking task by applying or releasing pressure against a fixed force transducer. Tasks were conducted at two speeds (“slow” being one tracking cycle in 10 s; and “fast” being two tracking cycles in 10 s) and compared to a visuomotor static task at a similar muscle contraction level. Results showed corticospinal changes with significant increases (p = 0.002) in excitability demonstrated during Study I (42.3 ± 16.8%) and Study II (56.3 ± 34.2%) slow speed tasks. Moreover, significant reduction in corticospinal inhibition was also observed during both tracking tasks at slow (59.3 ± 13.7%; p = 0.001) and fast speeds (31.9 ± 12.3%; p = 0.001). The findings may provide information on the underlying physiology during the early stages of motor skill acquisition.

Excitability at the motoneuron pool and motor cortex is specifically modulated in lengthening compared to isometric contractions

Excitability at the motoneuron pool and motor cortex is specifically modulated in lengthening compared to isometric contractions. J Neurophysiol 101: 2030–2040, 2009. First published January 28, 2008; doi:10.1152/jn.91104.2008. Neural control of muscle contraction seems to be unique during muscle lengthening. The present study aimed to determine the specific sites of modulatory control for lengthening compared with isometric contractions. We used stimulation of the motor cortex and corticospinal tract to observe changes at the spinal and cortical levels. Motor-evoked potentials (MEPs) and cervicomedullary MEPs (CMEPs) were evoked in biceps brachii and brachioradialis during maximal and submaximal lengthening and isometric contractions at the same elbow angle. Sizes of CMEPs and MEPs were lower in lengthening contractions for both muscles (by 28 and 16%, respectively; P 0.01), but MEP-to-CMEP ratios increased (by 21%; P 0.05). These results indicate reduced excitability at the spinal level but enhanced motor cortical excitability for lengthening compared with isometric muscle contractions.

Differential modulation of spinal and corticospinal excitability during drop jumps

Previously it was shown that spinal excitability during hopping and drop jumping is high in the initial phase of ground contact when the muscle is stretched but decreases toward takeoff. To further understand motor control of stretch-shortening cycle, this study aimed to compare modulation of spinal and corticospinal excitability at distinct phases following ground contact in drop jump. Motor-evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) and H-reflexes were elicited at the time of the short (SLR)-, medium (MLR)-, and long (LLR, LLR2)-latency responses of the soleus muscle (SOL) after jumps from 31 cm height. MEPs and H-reflexes were expressed relative to the background electromyographic (EMG) activity. H-reflexes were highly facilitated at SLR (172%) and then progressively decreased (MLR = 133%; LLR = 123%; LLR2 = 110%). TMS showed no effect at SLR, MLR, and LLR, whereas MEPs were significantly facilitated at the LLR2 (122%; P = 0.003). Background EMG was highest at LLR and lowest at LLR2. Strong H-reflex facilitation at the beginning of the stance phase indicated significant contribution of Ia-afferent input to the α-motoneurons during this phase that then progressively declined toward takeoff. Conversely, corticospinal excitability was exclusively increased at the phase of push off (LLR2, ∼120 ms). It is argued that corticomotoneurons increased their excitability at LLR2. At LLR (∼90 ms), Ia-afferent transmission as well as corticospinal excitability was low, whereas background EMG was high. Therefore it is speculated that other sources, presumably subcortical in origin, contributed to the EMG activity at LLR in drop jumps.

Strength training of one limb increases corticomotor excitability projecting to the contralateral homologous limb

The contralateral transfer of strength following unilateral strength training (ULS) is thought to be due to changes within the nervous system. Using transcranial magnetic stimulation (TMS) we compared corticospinal responses following ULS of the right biceps brachii (BB) projecting to the untrained left BB. Motor evoked potentials (MEPs) were recorded from both BB of 23 individuals pre and post 4 weeks heavy load (80% of 1RM) ULS of right BB. TMS was delivered at intensities below active motor threshold (AMT) to saturation of the MEP (MEP_max). ULS resulted in a 28% increase in 1RM right BB strength, resulting in a 19.2% increase in contralateral strength of the left BB (p = .0001). There was a significant increase in MEP amplitude of 30.3% (p = .03), 33% (p = .05), and 26.5% (p = .01) at AMT, 20% above AMT and MEP_max respectively. No significant differences in silent period were seen at AMT, 20% above AMT or MEP_max. This study has demonstrated increased corticospinal excitability projecting to the untrained arm following heavy load ULS.