Inhibition Of Muscle Activity Research Articles

The Transcallosal Highway: The ipsilateral silent period as a neural biomarker for impaired corpus callosum communication in multiple sclerosis

Multiple sclerosis is a neurodegenerative disease that damages myelin sheath within the central nervous system. This axonal demyelination impacts communication between the brain's hemispheres in persons with multiple sclerosis (PwMS). Changes in transcallosal communication impairs the coordination of movements requiring precise temporal and spatial components such as lower extremity function during gait. These bilateral movements require constant communication across the corpus callosum to excite and inhibit specific muscle groups. The ipsilateral silent period (iSP) is an indirect marker of the magnitude for transcallosal inhibition. We hypothesize that the iSP may also serve as a neural biomarker for transcallosal impairments originating from the more affected hemisphere and highlight underlying mechanisms for gait asymmetries in PwMS. Our ongoing study utilizes transcranial magnetic stimulation to assess the inhibitory capacity between the brain's hemispheres (i.e., iSPs). A focal magnetic pulse is delivered to the first dorsal interosseous resulting in a suppression of muscle activity, thus reflecting inhibitory transcallosal communication. There is a lack of research analyzing directionality data between the more and less affected hemisphere in PwMS. Therefore, we evaluate outcome metrics dependent upon the individual's more affected hemisphere. Twenty-three PwMS completed the ongoing protocol and inhibitory metrics such as depth iSP% average, duration, depth iSP% max, transcallosal conduction time, and onset latency were collected. No statistically significant differences have been found between the two hemispheres in PwMS. However, beyond directionality data, our study is investigating gait coordination with overall inhibitory capacity. Walking coordination is quantified using a metric called phase coordination index (PCI). A greater PCI value reflects poorer gait coordination. We hypothesize those who demonstrate better gait coordination (lower PCI values), will have a greater iSP. These findings will determine the potential of iSPs as a neural biomarker to address gait asymmetries and stratify participants into individualized mobility rehabilitation protocols. Multiple sclerosis is a neurodegenerative disease that damages myelin sheath within the central nervous system. This axonal demyelination impacts communication between the brain's hemispheres in persons with multiple sclerosis (PwMS). Changes in transcallosal communication impairs the coordination of movements requiring precise temporal and spatial components such as lower extremity function during gait. These bilateral movements require constant communication across the corpus callosum to excite and inhibit specific muscle groups. The ipsilateral silent period (iSP) is an indirect marker of the magnitude for transcallosal inhibition. We hypothesize that the iSP may also serve as a neural biomarker for transcallosal impairments originating from the more affected hemisphere and highlight underlying mechanisms for gait asymmetries in PwMS. Our ongoing study utilizes transcranial magnetic stimulation to assess the inhibitory capacity between the brain's hemispheres (i.e., iSPs). A focal magnetic pulse is delivered to the first dorsal interosseous resulting in a suppression of muscle activity, thus reflecting inhibitory transcallosal communication. There is a lack of research analyzing directionality data between the more and less affected hemisphere in PwMS. Therefore, we evaluate outcome metrics dependent upon the individual's more affected hemisphere. Twenty-three PwMS completed the ongoing protocol and inhibitory metrics such as depth iSP% average, duration, depth iSP% max, transcallosal conduction time, and onset latency were collected. No statistically significant differences have been found between the two hemispheres in PwMS. However, beyond directionality data, our study is investigating gait coordination with overall inhibitory capacity. Walking coordination is quantified using a metric called phase coordination index (PCI). A greater PCI value reflects poorer gait coordination. We hypothesize those who demonstrate better gait coordination (lower PCI values), will have a greater iSP. These findings will determine the potential of iSPs as a neural biomarker to address gait asymmetries and stratify participants into individualized mobility rehabilitation protocols.

On Stopping Voluntary Muscle Relaxations and Contractions: Evidence for Shared Control Mechanisms and Muscle State-Specific Active Breaking.

Control of the body requires inhibiting complex actions, involving contracting and relaxing muscles. However, little is known of how voluntary commands to relax a muscle are cancelled. Action inhibition causes both suppression of muscle activity and the transient excitation of antagonist muscles, the latter being termed active breaking. We hypothesized that active breaking is present when stopping muscle relaxations. Stop signal experiments were used to compare the mechanisms of active breaking for muscle relaxations and contractions in male and female human participants. In experiments 1 and 2, go signals were presented that required participants to contract or relax their biceps or triceps muscle. Infrequent Stop signals occurred after fixed delays (0-500 ms), requiring that participants cancelled go commands. In experiment 3, participants increased (contract) or decreased (relax) an existing isometric finger abduction depending on the go signal, and cancelled these force changes whenever Stop signals occurred (dynamically adjusted delay). We found that muscle relaxations were stopped rapidly, met predictions of existing race models, and had Stop signal reaction times that correlated with those observed during the stopping of muscle contractions, suggesting shared control mechanisms. However, stopped relaxations were preceded by transient increases in electromyography (EMG), while stopped contractions were preceded by decreases in EMG, suggesting a later divergence of control. Muscle state-specific active breaking occurred simultaneously across muscles, consistent with a central origin. Our results indicate that the later stages of action inhibition involve separate excitatory and inhibitory pathways, which act automatically to cancel complex body movements.SIGNIFICANCE STATEMENT The mechanisms of how muscle relaxations are cancelled are poorly understood. We showed in three experiments involving multiple effectors that stopping muscle relaxations involves transient bursts of EMG activity, which resemble cocontraction and have onsets that correlate with Stop signal reaction time. Comparison with the stopping of matched muscle contractions showed that active breaking was muscle state specific, being positive for relaxations and negative for contractions. The two processes were also observed to co-occur in agonist-antagonist pairs, suggesting separate pathways. The rapid, automatic activation of both pathways may explain how complex actions can be stopped at any stage of their execution.

Warm-up with weighted bat and adjustment of upper limb muscle activity in bat swinging under movement correction conditions.

The effects of weighted bat warm-up on adjustment of upper limb muscle activity were investigated during baseball bat swinging under dynamic conditions that require a spatial and temporal adjustment of the swinging to hit a moving target. Seven male college baseball players participated in this study. Using a batting simulator, the task was to swing the standard bat coincident with the arrival timing and position of a moving target after three warm-up swings using a standard or weighted bat. There was no significant effect of weighted bat warm-up on muscle activity before impact associated with temporal or spatial movement corrections. However, lower inhibition of the extensor carpi ulnaris muscle activity was observed in a velocity-changed condition in the weighted bat warm-up, as compared to a standard bat warm-up. It is suggested that weighted bat warm-up decreases the adjustment ability associated with inhibition of muscle activation under movement correction conditions.

Motor consequences of experimentally induced limb pain: A systematic review

Compelling evidence exists that pain may affect the motor system, but it is unclear if different sources of peripheral limb pain exert selective effects on motor control. This systematic review evaluates the effects of experimental (sub)cutaneous pain, joint pain, muscle pain and tendon pain on the motor system in healthy humans. The results show that pain affects many components of motor processing at various levels of the nervous system, but that the effects of pain are largely irrespective of its source. Pain is associated with inhibition of muscle activity in the (painful) agonist and its non-painful antagonists and synergists, especially at higher intensities of muscle contraction. Despite the influence of pain on muscle activation, only subtle alterations were found in movement kinetics and kinematics. The performance of various motor tasks mostly remained unimpaired, presumably as a result of a redistribution of muscle activity, both within the (painful) agonist and among muscles involved in the task. At the most basic level of motor control, cutaneous pain caused amplification of the nociceptive withdrawal reflex, whereas insufficient evidence was found for systematic modulation of other spinal reflexes. At higher levels of motor control, pain was associated with decreased corticospinal excitability. Collectively, the findings show that short-lasting experimentally induced limb pain may induce immediate changes at all levels of motor control, irrespective of the source of pain. These changes facilitate protective and compensatory motor behaviour, and are discussed with regard to pertinent models on the effects of pain on motor control.

A variational Bayesian approach for the robust analysis of the cortical silent period from EMG recordings of brain stroke patients

Transcranial magnetic stimulation (TMS) is a powerful tool for the calculation of parameters related to the intracortical excitability and inhibition of the motor cortex. The cortical silent period (CSP) is one such parameter that corresponds to the suppression of muscle activity for a short period after a muscle response to TMS. The duration of the CSP is known to be correlated with the prognosis of brain stroke patients' motor ability. Current methods for the estimation of the CSP duration are very sensitive to the presence of noise. A variational Bayesian formulation of a manifold-constrained hidden Markov model is applied in this paper to the segmentation of a set of multivariate time series (MTS) of electromyographic recordings corresponding to stroke patients and control subjects. A novel index of variability associated to this model is defined and applied to the detection of the silent period interval of the signal and to the estimation of its duration. This model and its associated index are shown to behave robustly in the presence of noise and provide more reliable estimations than the current standard in clinical practice.

REM sleep atonia: responsible brain regions, quantification, and clinical implication.

Muscle tone is profoundly suppressed during rapid-eye-movement sleep. Two indices that quantify this muscle activity suppression were introduced: the tonic inhibition index (TII) and the phasic inhibition index (PII). TII expresses the shortening of phasic chin muscle activity, and PII indicates the degrees of suppression of the occurrence of phasic chin muscle activity in the period of the burst of rapid eye movements. TII increased significantly with age, while PII decreased significantly. TII was found to reach the adult level at 12.3 years of age, while PII decreased to the adult value at 0.4 years. According to this difference in age between their maturation, the human nervous systems involved in muscle activity suppression are hypothesized to comprise at least two independent systems. TII and PII are also hypothesized to be affected by the activity of the brainstem inhibitory centers, which might be implicated in the suppression of muscle activity during wakefulness as well.

Biphasic response to gut manipulation and temporal correlation of cellular infiltrates and muscle dysfunction in rat

Surgical manipulation of the intestine results in the massive movement of leukocytes into the intestinal muscularis at 24 hours. This is associated with muscle inhibition. The aim of this study was to temporally associate leukocyte extravasation with ileus after surgical manipulation. Rats underwent a simple manipulation of the small bowel and were killed at various times (0, 0.25, 0.5, 1, 3, 6, 12, and 24 hours) postoperatively. Jejunal circular-muscle contractile activity was assessed in a standard organ bath. Both extravasating and resident leukocytes were immunohistochemically stained in muscularis whole mounts. Contractile activity was significantly reduced immediately after surgery, but rapidly returned to control levels at 3 hours. After recovery, muscle function decreased at 12 and 24 hours (41% and 81%, respectively). The resident muscularis macrophage network demonstrated cellular activation 1 hour postoperatively. The number of leukocytes increased over time (neutrophils, 67.5-fold; monocytes, 98.2-fold; and mast cells, 47-fold at 24 hours). The functional results demonstrate a biphasic response in the suppression of muscle activity after surgical manipulation. Regression analysis (r2 = 0.998) of the temporal development of leukocyte infiltration and the protracted phase of muscle inhibition provides evidence for a correlation between cellular inflammation and postoperative dysmotility.

Development of REM sleep atonia

To study the functional development of neuronal systems that suppress muscle activity, we quantified the chronological change of atonia in rapid-eye-movement sleep (REMS). REMS atonia was quantified by the tonic and phasic inhibition indices (TII and PII). TII indicates the shortness of chin muscle activity, whereas PII standardizes the simultaneous occurrence of chin muscle activity and bursts of rapid eye movements. TII and PII were calculated in REMS of 135 polysomnographical recordings obtained in healthy humans from premature babies to a 77-year-old man. TII increased significantly with age, while PII decreased significantly. TII reached an adult level at preadolescence, while PII at early infancy. Human nervous systems involved in both tonic and phasic inhibition in REMS raise their activities with age. Since TII and PII reach adult levels at different ages, suppression of muscle activity is hypothesized to be mediated through at least 2 independent systems in humans.

Neural influence on the expression of acetylcholinesterase molecular forms in fast and slow rabbit skeletal muscles

With the aim of investigating the roles of motor innervation and activity on muscle characteristics, we studied the molecular forms of acetylcholinesterase (AChE) in fast-twitch (semimembranosus accessorius; SMa) and slow-twitch (semimembranosus proprius; SMp) muscles of the rabbit. We have shown that SMa and SMp express different patterns and tissue distribution of AChE forms and that the effect of long denervation varies with age. Three principal findings concerning expression of AChE molecular forms emerge from these studies. (1) The activity of AChE and the pattern of its molecular forms are particularly altered in adult denervated SMa and SMp muscles. AChE activity increases by 10-fold in both muscles, but asymmetric forms disappear in SMa and increase by 20-fold in SMp muscles. A similar alteration of AChE is found after tenotomy of these muscles, showing that the effect of denervation may be partly due to suppression of muscle activity. (2) The different changes occuring in the composition of AChE molecular forms in adult denervated SMa and SMp muscles are consistent with fluorescent staining with anti-AChE monoclonal antibodies and with DBA or VVA lectins, which bind to AChE asymmetric, collagen-tailed forms. These lectins poorly stain denervated SMa muscle surfaces but intensely stain neuromuscular junctions and extrasynaptic areas in denervated SMp muscle. (3) In contrast with the adult, denervation of 1-day-old muscles does not markedly modify the total amount of AChE or the proportions of its molecular forms, despite dramatic effects on muscle structure. These results are supported by studies of labeling with fluorescent DBA: the lectin only slightly stains the muscle fiber surface of denervated 15-day-old SMp muscle. Taken together, these data show that denervated muscles escape physiological regulation, producing increased levels of AChE with highly variable cellular distribution and patterns of molecular forms, depending on the age of operation and on the type of muscle.

Clinical effects and cervical tissue changes after treatment with 16, 16 dimethyl-trans Δ2 PGE 1 methylester in the first trimester

Cervagem pessaries, containing 1 mg of 16, 16-dimethyl-trans Δ 2-PGE 1 methylester, was administered in the posterior vaginal fornix 4 h before vacuum aspiration in the 1st trimester. The effects of cervical dilatation, cervical collagen metabolism and cervical smooth muscle activity were investigated. In treated women the mean cervical dilatation was 7.9 mm as compared with 3.9 mm in controls. The in vitro incorporation of 14C proline in cervical tissue as well as the hydrolytic activity against a synthetic “collagen-like” polypeptide was increased after treatment with cervagem. The cervical smooth muscle sensitivity to prostaglandins, as revealed by inhibition of muscle activity, was higher in treated women than in controls. It is concluded that cervical dilatation, as induced by cervagem, involves an adaptation of both connective tissue and smooth muscle components.

Parallel suppression of extensor muscle tone and respiration by stimulation of pontine dorsal tegmentum in decerebrate cat

This paper describes the pontine brainstem area responsible for the suppression of postural muscle tone as well as of respiration in acute precollicular-postmammilary decebrate (mesencephalic) cats. Stimulation of the dorsal part of the pontine tegmentum (DTF) along the midline (P4–P7, H-5 to H-6) decreased the bilateral tone of the hindlimb extensor muscles and the diaphragmatic activity. Tonic discharges of the extensor muscles were suppressed by DTF stimulation and the suppression of muscle activity continued for more than 5 min after termination of the stimulation. In contrast, the suppression of the diaphragmatic activity, which resulted in apnea in some of the animals tested, resumed in spite of the continuation of the stimulation. However, the rebound augmentation of the diaphragmatic activity appeared immediately after the termination of the stimulation. The existence of such a rebound phenomenon suggested that the suppressive effects on the diaphragmatic activity persisted during the entire period of the stimulation. The recovery of respiratory movements during the stimulation led us to suggest that the strong respiratory drives emerge to overcome the exerted DTF-elicited suppressive effects on respiration. In the paralyzed and vagotomized animal, the DTF-elicited suppressive effects on phrenic neural discharges were minimal when the end-tidal pCO 2 was set at a higher level than during spontaneous breathing.

Calcium and the alpha-action of catecholamines on guinea-pig taenia caeci.

1. The involvement of calcium in the alpha-action of adrenaline on guinea-pig taenia caeci was studied by measuring the changes in membrane potential and muscle contraction, using the sucrose-gap method, and by determining the (42)K efflux, in the presence of a beta-blocker (propranolol, 1.8 x 10(-6)m).2. In the presence of extracellular calcium, the hyperpolarization caused by adrenaline (3 x 10(-6)m) was sustained during the period of its application (5 min), both in active preparations (at 36 degrees C) and in quiescent muscle (22 degrees C). In the absence of calcium, adrenaline caused a transient hyperpolarization which was smaller at 36 degrees C than at 22 degrees C and passed off within 5 min, while adrenaline was present.3. Both the sustained and the transient hyperpolarization were associated with an increase in (42)K efflux which had a similar time course. (42)K flux measurements were made in depolarized tissue (52.8 mm-potassium), in which the effect was consistent and more pronounced than in polarized muscle (2.8 mm-potassium).4. The transient hyperpolarization which is resistant to calcium removal and EGTA (0.1-2.0 mm) could be evoked only once but, following a short exposure to calcium (2.5 mm) for 20 sec and readmission of calcium-free medium, it was restored.5. The sustained and the transient hyperpolarization and the increase in (42)K efflux were abolished by the alpha-antagonist phentolamine (10(-5)m); their amplitude was dependent on the adrenaline concentration in the range 10(-7) to 3 x 10(-6)m, and both responses persisted in the absence of sodium or chloride.6. The hyperpolarization and the increase in (42)K efflux were greater at higher external calcium concentrations (0.3-2.5 mm).7. Cobalt (0.6 mm), D600 (2.5 x 10(-5)m) and the bee toxin apamin (10(-7)m) reduced the alpha-response.8. In the presence of apamin, in calcium-containing solution, the sustained hyperpolarization caused by adrenaline was preceded by, or converted to, depolarization, spike discharge and contraction.9. The depolarizing effect of adrenaline in the presence of apamin persisted in sodium-free or chloride-free medium, but was blocked in the absence of calcium and diminished by cobalt and D600.10. It is concluded that the alpha-response of guinea-pig taenia caeci consists of two components, both involving calcium. First, the activation of alpha-receptors increases calcium entry, which leads to the opening of potassium channels, a sustained hyperpolarization and inhibition of muscle activity. Secondly, in the absence of external calcium, a transient hyperpolarization is revealed, presumably due to the release of bound calcium from a limited cellular store which can be replenished by addition of external calcium, and this leads to an increase in potassium permeability.

Control of pharyngeal cavity size for English voiced and voiceless stops.

This study reports on pharyngeal cavity size change mechanisms associated with voiced−voiceless stop contrast in English. Electromyographic recordings were obtained from pharyngeal and infrahyoid muscles of three speakers, using bipolar, hooked−wire electrodes. The EMG potentials were sampled and averaged under computer control. The utterances sampled were 27 pairs of nonsense disyllables that contrasted only in the voicing of one stop consonant. All the English stop cognate pairs were included. Two modes of expanding the pharynx for voiced stops are proposed, each applying to a different group of muscles; an ’’active’’ mode, requiring increased muscle activity to expand the pharynx; and a ’’passive’’ mode, requiring suppression of muscle activity to expand the pharynx. The data reveal different patterns of use of the two expansion modes for the three subjects. The results are discussed in terms of current phonological theory. Subject Classification: 70.20.

Operant conditioning of specific patterns of neural and muscular activity.

In awake monkeys we recorded activity of single "motor" cortex cells, four contralateral arm muscles, and elbow position, while operantly reinforcing several patterns of motor activity. With the monkey's arm held semiprone in a cast hinged at the elbow, we reinforced active elbow movements and tested cell responses to passive elbow movements. With the cast immobilized we reinforced isometric contraction of each of the four muscles in isolation, and bursts of cortical cell activity with and without simultaneous suppression of muscle activity. Correlations between a precentral cell and specific arm muscles consistently appeared under several behavioral conditions, but could be dissociated by reinforcing cell activity and muscle suppression.