Michael A. Nordstrom

Estimating the strength of common input to human motoneurons from the cross‐correlogram.

1. The relationship between the motor unit discharge pattern (rate and variability) and synchronization of motor unit pairs was studied in the first dorsal interosseus muscle of human subjects. In separate trials of up to 4 min duration, subjects voluntarily controlled the mean discharge rate of an identified motor unit at one of several prescribed rates (range 7.5‐17.5 Hz). 2. The effect of discharge rate on the synchronous peak in the cross‐correlogram was examined in eighty motor unit pairs from six subjects. Five commonly used synchronization indices were used to quantify synchrony in the cross‐correlograms constructed from different discharge‐rate trials. For each synchronization index, the apparent magnitude of synchrony increased at lower motor unit discharge rates. The synchronization indices were not equally sensitive to discharge rate; increases in the different indices ranged from 72 to 494% between the highest and lowest discharge rates. 3. A model of the membrane potential trajectory underlying rhythmic motoneuron discharge was used to explain the observed increase in the magnitude of the synchronization indices at lower discharge rates. The essential feature of this model is that the probability of a common‐input EPSP causing a synchronous discharge in two motoneurons is independent of discharge rate. This means that the number of synchronous action potentials in excess of chance in any trial depends on the properties of the common‐input EPSPs and the duration of the trial, but is not related to motor unit discharge rates. The model also demonstrated that when the excess synchronous counts are normalized to motor unit discharge rate, or baseline counts in the histogram (as in the conventional synchronization indices), the magnitude of the index increases when the motor unit discharge rates are low. 4. The strength of common input to motoneurons could be misinterpreted if conventional synchronization indices are used because of discharge‐rate effects. The model was used to derive an index of the strength of common input to motoneurons (CIS) that was independent of motor unit discharge rate. CIS is the frequency of synchronous action potentials in the motor unit pair in excess of those expected due to chance (calculated during periods of tonic discharge in both units). The mean CIS in first dorsal interosseus motor unit pairs ranged from 0.052 to 1.005 extra synchronous action potentials per second across subjects. 5. Discharge variability was correlated with each of the synchronization indices and the CIS.(ABSTRACT TRUNCATED AT 400 WORDS)

Motor unit discharge and force tremor in skill-and strength-trained individuals

Abstract We examined motor unit (MU) discharge properties (mean interspike interval, ISI, discharge variability, short-term synchronization, common drive) and force tremor in the first dorsal interosseous (FDI) muscle of five musicians (skill-trained), five weight-lifters (strength-trained) and six untrained subjects during low-force isometric abduction of the index finger. Mean MU ISI was slightly shorter in skill-trained subjects than in untrained subjects. Discharge variability of FDI MUs did not differ significantly between groups. The mean strength of MU synchronization (expressed as the frequency of extra synchronous discharges above chance) was different in skill-trained (0.22±0.02 s–1, 162 MU pairs), untrained (0.32±0.02 s–1, 199 MU pairs) and strength-trained subjects (0.44±0.03 s–1, 183 MU pairs). FDI MU synchrony was weak and of equivalent strength in both hands of skill-trained subjects and the dominant (skilled) hand of untrained subjects. The stronger FDI MU synchrony in the non-dominant hand of untrained subjects was equivalent to that found in both hands of strength-trained subjects. The extent of common modulation of firing rates (common drive) was assessed for a subset of MU pairs and was weaker in skill-trained subjects (0.30±0.04, n=14) than untrained (0.43±0.3, n=14) and strength-trained (0.48±0.03, n=21) subjects. Force tremor was quantified for each hand in the same subjects during isometric index finger abduction at target forces of 0.5 N and 3.5 N. Tremor rms amplitude and peak power in the force frequency spectrum were significantly lower in skill-trained subjects than strength-trained subjects with the 3.5-N target force. The peak tremor frequency was similar in the three groups. The relatively more independent discharge of pairs of FDI MUs in skill-trained subjects was not responsible for the reduced tremor amplitudes in these subjects. Correlations between the overall extent of MU synchrony and common drive in FDI muscles and tremor measures obtained during the same experimental session were all non-significant. Differences in the central descending command signals are the most likely explanation for the more independent discharge of FDI MUs in skill-trained hands, while neural or peripheral muscular factors may be responsible for the weaker tremor.

Cortisol Inhibits Neuroplasticity Induction in Human Motor Cortex

We investigated whether plasticity of human motor cortex (M1) is influenced by time of day, and whether changes in circulating levels of cortisol contribute to this effect. Neuroplasticity was induced using paired associative stimulation (PAS), involving electrical stimulation of left median nerve, paired with transcranial magnetic stimulation over the right M1 25 ms later (90 pairs at 0.05 Hz). Surface EMG was recorded from the left abductor pollicis brevis (APB) and first dorsal interosseous muscle. Cortisol levels were assessed from saliva. Time-of-day modulation of PAS effectiveness was assessed in 25 subjects who were tested twice, at 8:00 A.M. and 8:00 P.M. on separate days. In a second double-blind study, 17 subjects were tested with PAS at 8:00 P.M. on two occasions after administration of oral hydrocortisone (24 mg) or placebo. The motor-evoked potential (MEP) in resting APB increased significantly after PAS in the evening (when endogenous cortisol levels were low), but not in the morning. Oral hydrocortisone prevented facilitation of the APB MEP after PAS, and in the drug study, mean salivary cortisol levels were negatively associated with PAS effectiveness. The GABAB-mediated cortical silent period for APB was longer in the morning than in the evening, and was lengthened by PAS and oral hydrocortisone. We conclude that neuroplasticity in human M1 and GABAB-dependent intracortical inhibitory systems are influenced by time of day and modified by circulating levels of cortisol.

Corticomotor plasticity and learning of a ballistic thumb training task are diminished in older adults

This study examined changes in corticomotor excitability and plasticity after a thumb abduction training task in young and old adults. Electromyographic (EMG) recordings were obtained from right abductor pollicis brevis (APB, target muscle) and abductor digiti minimi (ADM, control muscle) in 14 young (18-24 yr) and 14 old (61-82 yr) adults. The training task consisted of 300 ballistic abductions of the right thumb to maximize peak thumb abduction acceleration (TAAcc). Transcranial magnetic stimulation (TMS) of the left primary motor cortex was used to assess changes in APB and ADM motor evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) before, immediately after, and 30 min after training. No differences in corticomotor excitability (resting and active TMS thresholds, MEP input-output curves) or SICI were observed in young and old adults before training. Motor training resulted in improvements in peak TAAcc in young (177% improvement, P < 0.001) and old (124%, P = 0.005) subjects, with greater improvements in young subjects (P = 0.002). Different thumb kinematics were observed during task performance, with increases in APB EMG related to improvements in peak TAAcc in young (r(2) = 0.46, P = 0.008) but not old (r(2) = 0.09, P = 0.3) adults. After training, APB MEPs were 50% larger (P < 0.001 compared with before) in young subjects, with no change after training in old subjects (P = 0.49), suggesting reduced use-dependent corticomotor plasticity with advancing age. These changes were specific to APB, because no training-related change in MEP amplitude was observed in ADM. No significant association was observed between change in APB MEP and improvement in TAAcc with training in individual young and old subjects. SICI remained unchanged after training in both groups, suggesting that it was not responsible for the diminished use-dependent corticomotor plasticity for this task in older adults.

Differential Modulation of Intracortical Inhibition in Human Motor Cortex during Selective Activation of an Intrinsic Hand Muscle

Paired‐pulse transcranial magnetic stimulation (TMS) was used to assess the effectiveness of intracortical inhibition (ICI) acting on corticospinal neurons controlling three intrinsic hand muscles in humans. We hypothesised that the suppression of ICI with selective activation of a muscle would be restricted to corticospinal neurons controlling the muscle targeted for activation. Surface EMG was recorded from abductor pollicis brevis (APB), first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles of the left hand. Subjects were tested at rest and during weak selective activation of APB or ADM, while they attempted to keep the other muscles relaxed using visual feedback. Paired‐pulse TMS was applied with a circular coil oriented to produce antero‐posterior (AP) current flow in the right motor cortex (to preferentially evoke I3 waves in corticospinal neurons) and with postero‐anterior (PA) currents (to preferentially evoke I1 waves). Paired‐pulse TMS was less effective in suppressing the muscle evoked potential (MEP) when the muscle was targeted for selective activation, with both AP and PA stimulation. The mechanism for this includes effects on late I waves, as it was evident with a weak AP test TMS pulse that elicited negligible I1 waves in corticospinal neurons. ICI circuits activated by TMS, which exert their effects on late I waves but do not affect I1 waves, are strongly implicated in this modulation. With AP stimulation, paired‐pulse inhibition was not significantly altered for corticospinal neurons controlling other muscles of the same hand which were required to be inactive during the selective activation task. This differential modulation was not seen with PA stimulation, which preferentially activates I1 waves and evokes a MEP that is less influenced by ICI. The observations with AP stimulation suggest that selective activation of a hand muscle is accompanied by a selective suppression of ICI effects on the corticospinal neurons controlling that muscle. The pattern of differential modulation of ICI effectiveness with voluntary activation suggests that the ICI circuits assist the corticospinal system in producing fractionated activity of intrinsic hand muscles.

Adaptation of cat motoneurons to sustained and intermittent extracellular activation.

1. The main purpose of this study was to quantify the adaptation of spinal motoneurons to sustained and intermittent activation, using an extracellular route of stimulating current application to single test cells, in contrast to an intracellular route, as has been used previously. In addition, associations were tested between firing rate properties of the tested cells and other type (size)‐related properties of these cells and their motor units. 2. Motoneurons supplying the medial gastrocnemius muscle of the deeply anaesthetized cat were stimulated for 240 s with microelectrodes which passed sustained extracellular current at 1.25 times the threshold for repetitive firing. Many cells were also tested following a rest period with intermittent 1 s current pulses (duration 600 ms) at the same relative stimulus strength. Cell discharge was assessed from the EMG of the motor unit innervated by the test neuron. The motoneurons and their motor units were assigned to four categories (i.e. types FF, FR, S and F; where F = FF + FR) based on conventional criteria. In all, twenty F (16 FF, 4 FR) and fourteen S cells were studied with sustained stimulation. Thirty of these cells (17 F, 13 S) and an additional two cells (1 F, 1 S) were studied with intermittent stimulation. 3. The mean threshold current required for sustained firing for a period of > or = 2 s was not significantly different for F and S cells. However, most of the other measured parameters of motoneuron firing differed significantly for these two cell groups. For example, at 1.25 times the threshold current for repetitive firing, the mean firing duration in response to 240 s of sustained activation was 123 +/‐ 88 s (+/‐ S.D.) for F cells vs. 233 +/‐ 19 s for S cells. These values were significantly longer than those from a comparable, previously reported study that employed intracellular stimulation. With intermittent stimulation, the firing durations of F and S cells were not significantly different from each other. 4. All cells exhibited a delay from the onset of current to the first spike, followed by a brief accelerating discharge that was followed by a slower drop in firing rate. Some cells (21 of 34 with sustained activation; 20 of 32 with intermittent) exhibited doublet discharges (interspike intervals < or = 10 ms) that were intermingled with the more predominant singlet discharges. Doublets were more common in the S cell type.(ABSTRACT TRUNCATED AT 400 WORDS)

Motor Unit Synchronization Is Increased in Biceps Brachii After Exercise-Induced Damage to Elbow Flexor Muscles

The purpose of this study was to determine the effect of eccentric exercise on correlated motor unit discharge (motor unit synchronization and coherence) during low-force contractions of the human biceps brachii muscle. Eight subjects (age, 25 +/- 7 yr) performed three tasks involving isometric contraction of elbow flexors while EMG (surface and intramuscular) records were obtained from biceps brachii. Tasks were 1) maximum voluntary contraction (MVC); 2) constant-force contraction at various submaximal targets; and 3) sustained discharge of pairs of concurrently active motor units for 2-5 min. These tasks were performed before, immediately after, and 24 h after fatiguing eccentric exercise. MVC force declined 46% immediately after eccentric exercise and remained depressed (31%) 24 h later, which is indicative of muscle damage. For the constant-force task, biceps brachii EMG ( approximately 100% greater) and force fluctuations ( approximately 75% greater) increased immediately after exercise, and both recovered by approximately 50% 24 h later. Motor unit synchronization, quantified by cross-correlation of motor unit pairs during low-force (1-26% MVC) contractions, was 30% greater immediately after (n = 105 pairs) and 24 h after exercise (n = 92 pairs) compared with before exercise (n = 99 pairs). Similarly, motor unit coherence at low (0-10 Hz) frequencies was 20% greater immediately after exercise and 34% greater 24 h later. These results indicate that the series of events leading to muscle damage from eccentric exercise alters the correlated behavior of human motor units in biceps brachii muscle for > or =24 h after the exercise.

Influence of handedness on motor unit discharge properties and force tremor

Discharge properties of motor units (MUs) in the first dorsal interosseous muscle (FDI) were studied in the dominant and non-dominant hands of six right-handed (RH) and six left-handed (LH) individuals. MU discharge rates and variability were similar in each hand in RH (186 MUs) and LH (160 MUs) subjects. MU synchronization was less prominent in the dominant hand of RH subjects, with 51% (45/88) of cross-correlograms of MU discharge having significant central peaks, compared with 81% (90/111) for the non-dominant hand. The strength of MU synchronization (expressed as the frequency of extra synchronous discharges above chance) was weaker in the dominant hand of right-handers (0.23 ± 0.03 s-1 vs 0.39 ± 0.03 s-1), and synchronous peaks from that hand were slightly broader. Four of six RH subjects had significant differences in synchronization between hands (weaker in dominant hand). In contrast, left-handers had similar incidence (80 vs 82%, n = 161) and strength (0.41 ± 0.03 s-1 vs 0.37 ± 0.03 s-1) of MU synchrony in dominant and non-dominant hands. No LH subject had a significant difference in synchronization between hands. Force tremor was quantified in each hand in the same subjects during isometric abduction of FDI at 0.5 N and 3.5 N, and directly correlated with the extent of MU synchronization in the muscle. Tremor root mean square amplitude was similar in dominant and non-dominant hands. Power spectral analysis of the tremor force revealed that the peak frequency in the power spectrum was not influenced by handedness, but power at the peak frequency was higher in the non-dominant hand of RH subjects. Correlations between MU discharge variability and synchrony with measures of tremor amplitude were weak. The reduced MU synchronization in the dominant hand of right-handers may reflect a more restricted distribution of direct projections from motor cortical neurons within the FDI motoneuron pool, or reduced excitability of the cortical neurons during the task. These differences in MU synchronization, however, had an insignificant influence on the magnitude of physiological tremor in the FDI.

Reflex responses of motor units in human masseter muscle to electrical stimulation of the lip

SummaryThe reflex responses of single motor units in human masseter muscle to electrical stimulation of the lip were recorded. The subject maintained a contant mean level of pre-stimulus excitation of the parent motor neurone by biting in such a way that the unit fired at either 10 or 15 Hz during each trial. When firing at 10 Hz, most units were reflexly inhibited for up to 90 ms by electrical stimuli at intensities that were perceived to be mildly uncomfortable. In many units, the inhibition consisted of 2 phases which were separated from each other by a few spikes occurring about 30 ms after the stimulus. It was occasionally possible to evoke only the later phase (latency about 40 ms) with stimuli at intensities near the response threshold. In these instances, the inhibitory response became biphasic at higher stimulus intensities with the emergence of a shorter (10–15 ms) component. Still higher intensities caused the 2 phases of inhibition to merge, giving the appearance of a single, prolonged, inhibitory response. When the pre-stimulus firing frequency of the unit was changed from 10 Hz to 15 Hz, the inhibitory responses to the same stimuli were decreased, with the longer-latency component usually surviving beyond the shorter-latency phase. The pattern of reflex responses observed can be explained by a model based on information derived from intracellular recordings in animal experiments.

Relationship between motor unit short-term synchronization and common drive in human first dorsal interosseous muscle.

We assessed the strength of motor unit (MU) short-term synchronization and common fluctuations in mean firing rate (common drive) in the same pairs of MUs in order to evaluate whether these features of voluntary MU discharge arise from a common mechanism. Shared, branched-axon inputs, with the most important being widely divergent monosynaptic projections to motoneurons from motor cortical cells, are regarded as the principal determinants of MU short-term synchronization. It is not known to what extent these synaptic inputs are responsible for common drive behaviour of MUs. MU spike trains from 77 pairs of concurrently active MUs in first dorsal interosseous muscle of 17 subjects were discriminated with the high reliability needed for common drive analysis. For each MU pair, the data used for comparison of the two analyses of correlated MU discharge came from a single trial (1-5 min duration) of isometric abduction of the index finger. Linear regression revealed a weak, significant positive correlation between the strength of MU short-term synchronization and the strength of common drive in the MU pairs (r2 = 0.06, P < 0.05, n = 77), which was slightly stronger when MU pairs with broad synchronous peaks (> 20 ms) were excluded (r2 = 0.09, P < 0.05, n = 63). These data suggest that less than 10% of the variation in the strength of common drive exhibited by pairs of MUs could be accounted for by differences in the strength of MU short-term synchronization. These two phenomena are therefore likely to arise predominantly from separate mechanisms. At least under these task conditions, the widely divergent, branched-axon inputs from single corticospinal neurons which are important in the generation of MU short-term synchronization play only a minor role in the production of common drive of MU discharge rates.