The Effects of Nitrate-Rich Supplementation on Neuromuscular Efficiency during Heavy Resistance Exercise.

OBJECTIVE: Nitrate-rich (NR) supplements can enhance exercise performance by improving neuromuscular function and the aerobic cost of exercise. However, little is known about the effects of nitrate on dynamic, multijoint resistance exercise. METHODS: Fourteen resistance-trained men (age, 21.1 ± 0.9 years; height, 173.2 ± 2.9 cm: body mass, 77.6 ± 4.3 kg; squat one-repetition maximum [1RM], 127.5 ± 18.8 kg) participated in a randomized, double-blind, crossover experiment. Subjects consumed an NR or nitrate-poor (NP) supplement for 3 days, performed a bout of heavy resistance exercise, completed a washout, and then repeated the procedures with the remaining supplement. Before, during, and after exercise, individual and gross motor unit efficiency was assessed during isometric and dynamic muscle contractions. In addition, we compared physical performance, heart rate, lactate, and oxygen consumption (VO2). RESULTS: Nitrate-rich supplementation resulted in lower initial muscle firing rates at rest and lower mean and maximum firing rates over the course of fatiguing exercise. Nitrate-poor supplementation was accompanied by increased mean and maximum firing rates by the end of exercise and lower initial firing rates. In addition, NR supplementation resulted in higher mean peak electromyography (EMG) amplitudes. Heart rate, lactate, and physical performance did not differ by treatment, but oxygen consumption increased more frequently when the NP supplement was consumed. CONCLUSION: Supplementation with an NR beetroot extract-based supplement provided neuromuscular advantages during metabolically taxing resistance exercise.

Columnar interactions determine horizontal propagation of recurrent network activity in neocortex.

The cortex is organized in vertical and horizontal circuits that determine the spatiotemporal properties of distributed cortical activity. Despite detailed knowledge of synaptic interactions among individual cells in the neocortex, little is known about the rules governing interactions among local populations. Here, we used self-sustained recurrent activity generated in cortex, also known as up-states, in rat thalamocortical slices in vitro to understand interactions among laminar and horizontal circuits. By means of intracellular recordings and fast optical imaging with voltage-sensitive dyes, we show that single thalamic inputs activate the cortical column in a preferential layer 4 (L4) → layer 2/3 (L2/3) → layer 5 (L5) sequence, followed by horizontal propagation with a leading front in supragranular and infragranular layers. To understand the laminar and columnar interactions, we used focal injections of TTX to block activity in small local populations, while preserving functional connectivity in the rest of the network. We show that L2/3 alone, without underlying L5, does not generate self-sustained activity and is inefficient propagating activity horizontally. In contrast, L5 sustains activity in the absence of L2/3 and is necessary and sufficient to propagate activity horizontally. However, loss of L2/3 delays horizontal propagation via L5. Finally, L5 amplifies activity in L2/3. Our results show for the first time that columnar interactions between supragranular and infragranular layers are required for the normal propagation of activity in the neocortex. Our data suggest that supragranular and infragranular circuits, with their specific and complex set of inputs and outputs, work in tandem to determine the patterns of cortical activation observed in vivo.

Effect of a peripheral nerve block on torque produced by repetitive electrical stimulation.

Neuromuscular electrical stimulation (NMES) generates contractions by activation of motor axons (peripheral mechanism), but the afferent volley also contributes by recruiting spinal motoneurons synaptically (central mechanism), which recruits motoneurons according to Henneman's size principle. Thus, we hypothesized that contractions that develop due to a combination of peripheral and central mechanisms will fatigue less rapidly than when electrically evoked contractions are generated by the activation of motor axons alone. Plantar-flexion torque evoked by NMES over the triceps surae was compared in five able-bodied subjects before (Intact) and during (Blocked) a complete anesthetic block of the tibial and common peroneal nerves. In the Blocked condition, plantar-flexion torque could only develop from the direct activation of motor axons beneath the stimulating electrodes. NMES was delivered using three protocols: protocol A, constant 100 Hz for 30 s; protocol B, four 2-s bursts of 100 Hz alternating with 20-Hz stimulation; and protocol C, alternating 100 Hz bursts (1 s on, 1 s off) for 30 s. The percent change in evoked plantar flexion torque from the beginning to the end of the stimulation differed (P < 0.05) between Intact and Blocked conditions for all protocols (Intact: protocol A = +125%, B = +230%, C = +78%; Blocked: protocol A = -79%, B = -15%, C = -35%). These results corroborate previous evidence that NMES can evoke contractions via the recruitment of spinal motoneurons in addition to the direct recruitment of motor axons. We now show that NMES delivered for periods of up to 30 s generates plantar-flexion torque which decreases when only motor axons are recruited and increases when the central nervous system can contribute.

Pregabalin exerts oppositional effects on different inhibitory circuits in human motor cortex: a double-blind, placebo-controlled transcranial magnetic stimulation study.

PURPOSE: To explore acute effects of pregabalin (PGB) on human motor cortex excitability with transcranial magnetic stimulation (TMS). METHODS: PGB, 600 mg/day, was orally administered in 19 healthy subjects twice daily in a randomized, double-blind, placebo-controlled crossover design. Several measures of motor cortex excitability were tested with single- and paired-pulse TMS. RESULTS: Mean short-interval intracortical inhibition (SICI) was reduced after PGB (74 +/- 7% of unconditioned response) compared with placebo (60 +/- 6% of unconditioned response). In contrast, mean long-interval intracortical inhibition (LICI) was increased by PGB (26 +/- 4% of unconditioned response) compared with placebo (45 +/- 8% of unconditioned response), and mean cortical silent period (CSP) showed an increase from 139 +/- 8 ms or 145 +/- 8 ms after placebo to 162 +/- 7 ms or 161 +/- 10 ms after PGB. Motor thresholds, intracortical facilitation, and corticospinal excitability were unaffected. CONCLUSIONS: The observed excitability changes with oppositional effects on SICI and LICI or CSP suggest gamma-aminobutyric acid (GABA)B-receptor activation. They are markedly distinct from those induced by gabapentin, although both PGB and gabapentin are thought to mediate their function by binding to the alpha2-delta subunit of voltage-gated calcium channels. Conversely, the TMS profile of PGB shows striking similarities with the pattern evoked by the GABA-reuptake inhibitor tiagabine.

Levetiracetam influences human motor cortex excitability mainly by modulation of ion channel function--a TMS study.

PURPOSE: Levetiracetam (LEV) is a new compound with anticonvulsive efficacy in focal and generalized epilepsies. Recent in vitro studies suggest LEV to act as a selective N-type-calcium-channel blocker. METHODS: We used transcranial magnetic stimulation (TMS) in order to investigate if ion-channel blockade is relevant to the inhibitory CNS effects of LEV in vivo and if motor thresholds (MTs) are a valid TMS parameter to detect this mode of action. In a double blind, placebo-controlled, crossover study, the effects of single oral doses of 500 and 2000 mg LEV on motor thresholds, recruitment curves (REC), cortical induced silent period (CSP) and on intracortical inhibition (ICI) and facilitation (ICF) were studied in 10 healthy subjects. RESULTS: A significant increase of motor thresholds was noticed after 2000 mg LEV as compared to placebo. The recruitment curve showed a trend towards motor evoked potential (MEP) amplitude reduction after LEV. LEV had no significant effect on CSP or on intracortical excitability as measured by inhibition and facilitation. CONCLUSIONS: We conclude that the modulation of ion-channel function, reflected by motor threshold elevation and a trend towards recruitment curve suppression, is relevant to the inhibitory CNS effects of LEV in vivo, and therefore, may contribute to the anticonvulsive efficacy of LEV. GABAergic or glutamatergic mechanisms seem to be less important in vivo as measured by TMS.

Modulation of human corticomotor excitability by somatosensory input.

In humans, somatosensory stimulation results in increased corticomotoneuronal excitability to the stimulated body parts. The purpose of this study was to investigate the underlying mechanisms. We recorded motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) from abductor pollicis brevis (APB), first dorsal interosseous (FDI), and abductor digiti minimi (ADM) muscles. MEP amplitudes, recruitment curves (RC), intracortical inhibition (ICI), intracortical facilitation (ICF), resting (rMT) and active motor thresholds (aMT) were recorded before and after a 2-h period of ulnar nerve electrical stimulation at the wrist. Somatosensory input was monitored by recording somatosensory evoked potentials. To differentiate excitability changes at cortical vs. subcortical sites, we recorded supramaximal peripheral M-responses and MEPs to brainstem electrical stimulation (BES). In order to investigate the involvement of GABAergic mechanisms, we studied the influence of lorazepam (LZ) (a GABA(A) receptor agonist) relative to that of dextromethorphan (DM) (an NMDA receptor antagonist) and placebo in a double-blind design. We found that somatosensory stimulation increased MEP amplitudes to TMS only in the ADM, confirming a previous report. This effect was blocked by LZ but not by either DM or placebo and lasted between 8 and 20 min in the absence of (i) changes in MEPs elicited by BES, (ii) amplitudes of early somatosensory-evoked potentials or (iii) M-responses. We conclude that somatosensory stimulation elicited a focal increase in corticomotoneuronal excitability that outlasts the stimulation period and probably occurs at cortical sites. The antagonistic effect of LZ supports the hypothesis of GABAergic involvement as an operating mechanism.

4-Aminopyridine-sensitive neurologic deficits in patients with spinal cord injury.

4-Aminopyridine (4-AP) is a potassium channel blocking agent with the ability to restore conduction in demyelinated internodes of axons of the spinal cord. The present investigation sought to obtain electrophysiologic evidence of the effect of 4-AP in ameliorating central conduction deficits in a group of patients (n = 6) with spinal cord injury (SCI). The group was selected on the basis of having temperature-dependent central conduction deficits. 4-AP (24-25 mg total dose) was delivered intravenously at 6 mgh-1 or 15 mgh-1 while somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) were recorded as indices of central conduction. Two patients exhibited marked increases in the amplitude of cortical SEPs, and in one of these, 4-AP brought about a reduced central conduction time from L1 to cortex. Four patients revealed increased amplitude MEPs with concomitant reduction in latency indicative of enhanced conduction in corticospinal or corticobulbospinal pathways. Two of these patients demonstrated increased voluntary motor unit recruitment following 4-AP. Clinical examination revealed reduced spasticity (n = 2), reduced pain (n = 1), increased sensation (n = 1), improved leg movement (n = 3), and restored voluntary control of bowel (n = 1). These results support the hypothesis that 4-AP induces neurologic benefits in some patients with SCI. They are also consistent with the emerging concept that pharmaceutical amelioration of central conduction deficits caused by focal demyelination may contribute to the management of a select group of patients with compressive or contusive SCI.

[Pharmacological properties of buprenorphine, a new analgesic agent. Part II. (author's transl)].

Pharmacological properties of buprenorphine were compared with those of morphine and pentazocine. Buprenorphine scarcely showed any effects on spontaneous EEGs and sleep-wakefulness cycles. Buprenorphine tended to depress the recruiting and augmenting responses and the spindle burst, and it also inhibited the hypothalamic arousal response. Buprenorphine had weaker emetic action than morphine and protected against apomorphine-induced emesis in the same manner as morphine. Buprenorphine scarcely affected respirations, blood pressure, heart rate, blood flow, ECG, cardiac contractile force, cornary flow, and intracranial pressure. However, morphine and pentazocine caused depressed respiration, decreased blood pressure, increased blood flow and cardiac contractile force, and elevated intracranial pressure. Buprenorphine, morphine, and pentazocine did not affect bile secretion, but produced contraction of the sphincter of Oddi. Buprenorphine had very little effect on renal function, but morphine and pentazocine reduced this function to depress urine flow. Buprenorphine and morphine inhibited carrageenin-induced edema. Buprenorphine had no effect on blood histamine level, but morphine increased the concentration of histamine. These results indicate that buprenorphine has little effect on the central nervous system, respiratory and cardiovascular system, and renal function.

Inhibitory action of the combination of aminopyrine and secobarbital on EEG activation, neocortical recruiting and augmenting responses in rabbits.

The effect of the combination of aminopyrine and secobarbital at a molar ratio of 2:1, the mixture and molecular compound, on rabbit EEG activation was examined. Secobarbital 40 mg/kg p.o. elevated threshold voltages in the neocortical and hippocampal EEG activation by high frequency electrical stimulation of the midbrain reticular formation (MRF), nucleus centralis medialis (CM) of the thalamus, and posterior hypothalamus (PHA) by 40, 40 and 80% respectively. Aminopyrine 80 mg/kg p.o. alone did not affect the arousal responses. The molecular compound 120 mg/kg p.o. has more potent and long-lasting actions in inhibiting the arousal responses induced by the stimulation of MRF (80%) and CM (50%) than with secobarbital alone. The inhibitory action of the mixture 120 mg/kg p.o. on the PHA-arousal response (40%) was significantly weaker than that of the molecular compound (80%). Secobarbital and the molecular compound slightly inhibited the neocortical augmenting and recruiting responses. Our findings suggest that although aminopyrine exerts a synergistic effect with secobarbital in inhibiting the EEG activation produced by MRF stimulation, in inhibiting the PHA-arousal response, there is no synergistic effect of the two drugs when they were given as the mixture. Moreover, the molecular compound rather than the mixture has a more potent inhibitory action on the EEG activation, particularly with PHA stimulation.

[Pharmacological studies on Zingiber Mioga (2). Effects of water extracts on the central nervous system (author's transl)].

Effects on the cat central nervous system of water extracts of Zingiber Mioga (ZM) were studied by electroencephalography (EEG). ZM had little effect on the EEG arousal response to electrical stimulation of mid-brain reticular formation. ZM (3 approximately 5 mg/kg, i.v.) suppressed the recruiting response and the augmenting response recorded from the posterior sigmoid gyrus, respectively. ZM (1 approximately 3 mg/kg, i.v.) decreased the photic driving response, while 5 mg/kg, i.v., tended to enhance the response. In the chronic experiments, ZM(1 approximately 3 mg/kg, i.v.) induced a drowsy pattern in the cortex and subcortex, and shortened the lasting time of the EEG arousal response to sonic stimulation. After 5 to 10 minutes, behavior showed a drowsy to light sleeping state, and electromyogram recorded from the platysma showed a decreased amplitude and frequency, but, did not have an inhibitory effect on the motor system, (ataxia). ZM (5 mg/kg, i.v.) induced desynchronization in the cortex and subcortex, arousal wave appeared in hippocampus, midbrain reticular formation, nucl. ventralis postero-lateralis and amygdala, and behavior tended toward the awake stage. After 10 minutes, EEG transferred to a drowsy pattern and behavior showed a drowsy to light sleeping state. The animal could be readily awakened by sonic stimulation, at every time. ZM appears to have an inhibitory effect on the central nervous system.

[Behavioral and EEG effects of Zingiber mioga Roscoe (water soluble fraction) (author's transl)].

Behavioral and EEG effects of water soluble fraction extracted from Zingiber mioga Roscoe (Z. mioga) were investigated in mice, rats and rabbits. Z. mioga was dissolved in isotonic saline and given i.p. into mice and rats, and i.v. into rabbits, respectively. Z. mioga at doses of 50 approximately 400 mg/kf produced a marked reduction in locomotor activity of mice in the open-field test. The peak time of reduction was 30 min after the injection. In mice, Z. mioga at the same doses lowered significantly the rectal temperature and prolonged the sleeping time induced by thiopental-Na (40 mg/kg, i.v.). Z. mioga at a dose of 400 mg/kg had no anticonvulsant effects and it produced a slight muscle relaxation in mice. Z. mioga at doses of 50 approximately 200 mg/kg induced a significant inhibition of the active conditioned avoidance response of the rat in a shuttle box without affecting the unconditioned escape response. In the step-down method, however, the passive conditioned avoidance response was rarely affected by Z. mioga, but the response was suppressed by chlorpromazine. In rabbits with chronically implanted electrodes, Z. mioga at doses of 20--30 mg/kg induced a drowsy pattern of spontaneous EEG, ilel high voltage slow waves in the neocortex and amygdala, and desynchronization in the case of hippocampal theta waves. The EEG arousal response to the external auditory stimulation was inhibited by the same doses of Z. mioga, whereas it failed to suppress the arousal response to either the midbrain reticular or posterior hypothalamic stimulation, as with chlorpromazine. Neither the recruiting response nor the photic driving response were affected by Z. mioga. On the other hand, the limbic after-discharges to the hippocampal or amygdaloid stimulation were enhanced by Z. mioga as well as chlorpromazin, but they were inhibited by diazepam. The EEG effects of Z. mioga were qualitatively similar to chlorpromazine, but not to diazepam. These results indicate the similarity of behavioral and EEG effects of Z. mioga to those seen with neuroleptics such as chlorpromazine.

Pre and post-glycerol special audiometric tests battery results in endolymphatic hydrops.

The glycerol test for endolymphatic hydrops was administered to 17 patients exhibiting classical symptoms of Meniere's disease. A complete battery of audiometric tests including the SISI, TTD (Rosenberg variation). ABLB, Sweep Frequency Bekesy, two tests of speech discrimination (Rush Hughes and Northwestern), and air and bone conduction thresholds were administered pre and post-glycerol ingestion in order to determine the effect of osmotic diuresis. Improvement in pure-tone sensitivity and speech discrimination scores were most often observed. Among the special audiometric tests only the SISI scores exhibited changes, however, these could be related to the threshold changes. There were no significant differences observed in the threshold tone decay tests nor in the ABLB. The sweep frequency Bekesy test revealed only the changes which were observed in pure-tone sensitivity.

Effects of selected drugs on an auditory or thalamic conditioned stimulus eliciting recruitment in the cat.

Minimally effective oral doses of chlorpromazine, imipramine, and pentobarbital necessary to block a discrete trial (bar-press) conditioned avoidance response were compared in cats chronically implanted with electrodes over the cerebral cortex and in the nucleus centralis medialis of the thalamus. Three conditioned stimulus contingencies consisting of tone and low or high voltage thalamic stimulation were presented. Minimal conditioned response blocking doses of these agents produced only slight qualitative changes in cortically recorded recruitment. Drug treatment affected the conditioned stimulus contingencies differentially, and the rank order in terms of ease of disruption of the conditioned avoidance response was high voltage thalamic conditioned stimulus greater than low voltage thalamic conditioned stimulus greater than auditory conditioned stimulus. The differential effect of these drugs might have been due to the additive inhibition of these agents and the thalamic conditioned stimulus on performance. With the exception of chlorpromazine, the behavioral effects of these drugs and their effects on recruitment were dissociated.