Different Stimulation Frequencies Alter Synchronous Fluctuations in Motor Evoked Potential Amplitude of Intrinsic Hand Muscles-a TMS Study.

The amplitude of motor-evoked potentials (MEPs) elicited with transcranial magnetic stimulation (TMS) varies from trial-to-trial. Synchronous oscillations in cortical neuronal excitability contribute to this variability, however it is not known how different frequencies of stimulation influence MEP variability, and whether these oscillations are rhythmic or aperiodic. We stimulated the motor cortex with TMS at different regular (i.e., rhythmic) rates, and compared this with pseudo-random (aperiodic) timing. In 18 subjects, TMS was applied at three regular frequencies (0.05 Hz, 0.2 Hz, 1 Hz) and one aperiodic frequency (mean 0.2 Hz). MEPs (n = 50) were recorded from three intrinsic hand muscles of the left hand with different functional and anatomical relations. MEP amplitude correlation was highest for the functionally related muscle pair, less for the anatomically related muscle pair and least for the functionally- and anatomically-unrelated muscle pair. MEP correlations were greatest with 1 Hz, and least for stimulation at 0.05 Hz. Corticospinal neuron synchrony is higher with shorter TMS intervals. Further, corticospinal neuron synchrony is similar irrespective of whether the stimulation is periodic or aperiodic. These findings suggest TMS frequency is a crucial consideration for studies using TMS to probe correlated activity between muscle pairs.

Increased intracortical inhibition in elderly adults with anterior-posterior current flow: A TMS study.

OBJECTIVE: All previous studies using TMS to assess short-interval intracortical inhibition (SICI) in older adults have used a conventional coil orientation, which produces posterior-to-anterior (PA) current flow in the motor cortex. However, no studies have examined SICI in older adults by reversing the coil to induce anterior-to-posterior (AP) current flow, which is considered more sensitive at detecting SICI. Therefore, we investigated age-related changes in SICI using both PA and AP TMS across different conditioning stimulus intensities and muscle activation states. METHODS: In 22 young and 20 older adults, SICI was assessed using PA and AP coil orientations, across a range of conditioning stimulus intensities (70-90% active motor threshold), and whilst participants kept their first dorsal interosseous (FDI) muscle either relaxed or active (2N force). RESULTS: There were no age-related differences in SICI using conventional PA TMS in resting or active FDI muscle. However, SICI was increased in elderly participants when assessed with reverse coil AP TMS in resting FDI. CONCLUSIONS: Coil orientation is a key factor to consider when assessing age-related differences in SICI. SIGNIFICANCE: Reverse coil AP TMS can reveal age-related changes in SICI, which were previously not evident with conventional PA TMS. This may have implications for the assessment of SICI in some clinical populations that may show subtle differences in SICI circuitry.

Time of day does not modulate improvements in motor performance following a repetitive ballistic motor training task.

Repetitive performance of a task can result in learning. The neural mechanisms underpinning such use-dependent plasticity are influenced by several neuromodulators. Variations in neuromodulator levels may contribute to the variability in performance outcomes following training. Circulating levels of the neuromodulator cortisol change throughout the day. High cortisol levels inhibit neuroplasticity induced with a transcranial magnetic stimulation (TMS) paradigm that has similarities to use-dependent plasticity. The present study investigated whether performance changes following a motor training task are modulated by time of day and/or changes in endogenous cortisol levels. Motor training involving 30 minutes of repeated maximum left thumb abduction was undertaken by twenty-two participants twice, once in the morning (8 AM) and once in the evening (8 PM) on separate occasions. Saliva was assayed for cortisol concentration. Motor performance, quantified by measuring maximum left thumb abduction acceleration, significantly increased by 28% following training. Neuroplastic changes in corticomotor excitability of abductor pollicis brevis, quantified with TMS, increased significantly by 23% following training. Training-related motor performance improvements and neuroplasticity were unaffected by time of day and salivary cortisol concentration. Although similar neural elements and processes contribute to motor learning, training-induced neuroplasticity, and TMS-induced neuroplasticity, our findings suggest that the influence of time of day and cortisol differs for these three interventions.

Short-term synchrony in diverse motor nuclei presumed to receive different extents of direct cortical input.

Motor units within human muscles usually exhibit a significant degree of short-term synchronization. Such coincident spiking typically has been attributed to last-order projections that provide common synaptic input across motor neurons. The extent of branched input arising directly from cortical neurons has often been suggested as a critical factor determining the magnitude of short-term synchrony. The purpose of this study, therefore, was to quantify motor unit synchrony in a variety of human muscles differing in the presumed extent of cortical input to their respective motor nuclei. Cross-correlation histograms were generated from the firing times of 551 pairs of motor units in 16 human muscles. Motor unit synchrony tended to be weakest for proximal muscles and strongest for more distal muscles. Previous work in monkeys and humans has shown that the strength of cortical inputs to motor neurons also exhibits a similar proximal-to-distal gradient. However, in the present study, proximal-distal location was not an exclusive predictor of synchrony magnitude. The muscle that exhibited the least synchrony was an elbow flexor, whereas the greatest synchrony was most often found in intrinsic foot muscles. Furthermore, the strength of corticospinal inputs to the abductor hallucis muscle, an intrinsic foot muscle, as assessed through transcranial magnetic stimulation, was weaker than that projecting to the tibialis anterior muscle, even though the abductor hallucis muscle had higher synchrony values compared with the tibialis anterior muscle. We argue, therefore, that factors other than the potency of cortical inputs to motor neurons, such as the number of motor neurons innervating a muscle, significantly affects motor unit synchrony.

Adaptations in biceps brachii motor unit activity after repeated bouts of eccentric exercise in elbow flexor muscles.

The purpose of this study was to examine changes in motor unit activity in the biceps brachii muscle after an initial (Bout 1) and repeated (Bout 2) session of eccentric exercise separated by 1 wk. Eight subjects (aged 22 ± 2 yr) participated in experimental assessments of neuromuscular function obtained before, immediately after, 24 h after, and 7 days after each exercise bout. Each experimental session involved assessments of elbow-flexor force and biceps and triceps brachii electromyography during maximum voluntary isometric contractions (MVCs) and constant-force isometric contractions at five contraction intensities (5-50% MVC), along with indicators of muscle damage (muscle pain and passive tension). In addition, motor unit recordings were obtained before exercise, 7 days after Bout 1, and 24 h after Bout 2 to assess motor unit synchronization and recruitment thresholds. Following a single eccentric exercise session that elicited significant indicators of muscle damage, we found a 57% increase in motor unit synchronization 7 days later compared with before exercise, despite the recovery of maximal strength, soreness, and relaxed elbow-joint angle at this time. Furthermore, a second bout of the same eccentric exercise resulted in reduced indicators of muscle damage and a decline in the strength of motor unit synchronization (24 h after Bout 2) toward levels observed before both exercise sessions. In contrast, no changes in motor unit recruitment thresholds were observed 7 days after Bout 1 or 24 h after Bout 2 compared with before exercise. The increased motor unit synchronization 7 days after a single eccentric exercise session provides new evidence of changes in motor unit activity during the putative repair and regeneration phase following eccentric muscle damage.

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.

Eccentric muscle damage has variable effects on motor unit recruitment thresholds and discharge patterns in elbow flexor muscles.

The purpose of this study was to determine the effect of eccentric muscle damage on recruitment threshold force and repetitive discharge properties of low-threshold motor units. Ten subjects performed four tasks involving isometric contraction of elbow flexors while electromyographic (EMG) data were recorded from human biceps brachii and brachialis muscles. Tasks were 1) maximum voluntary contraction (MVC); 2) constant-force contraction at various submaximal targets; 3) motor unit recruitment threshold task; and 4) minimum motor unit discharge rate task. These tasks were performed on three separate days before, immediately after, and 24 h after eccentric exercise of elbow flexor muscles. MVC force declined (42%) immediately after exercise and remained depressed (29%) 24 h later, indicative of muscle damage. Mean motor unit recruitment threshold for biceps brachii was 8.4+/-4.2% MVC, (n=34) before eccentric exercise, and was reduced by 41% (5.0+/-3.0% MVC, n=34) immediately after and by 39% (5.2+/-2.5% MVC, n=34) 24 h after exercise. No significant changes in motor unit recruitment threshold were observed in the brachialis muscle. However, for the minimum tonic discharge rate task, motor units in both muscles discharged 11% faster (10.8+/-2.0 vs. 9.7+/-1.7 Hz) immediately after (n=29) exercise compared with that before (n=32). The minimum discharge rate variability was greater in brachialis muscle immediately after exercise (13.8+/-3.1%) compared with that before (11.9+/-3.1%) and 24 h after exercise (11.7+/-2.4%). No significant changes in minimum discharge rate variability were observed in the biceps brachii motor units after exercise. These results indicate that muscle damage from eccentric exercise alters motor unit recruitment thresholds for >or=24 h, but the effect is not the same in the different elbow flexor muscles.

Asymmetric activation of motor cortex controlling human anterior digastric muscles during speech and target-directed jaw movements.

Like most of the cranial muscles involved in speech, the trigeminally innervated anterior digastric muscles are controlled by descending corticobulbar projections from the primary motor cortex (M1) of each hemisphere. We hypothesized that changes in corticobulbar M1 excitability during speech production would show a hemispheric asymmetry favoring the left side, which is the dominant hemisphere for language processing in most strongly right handed subjects. Fifteen volunteers aged 24.5+/-5.3 (SD) yr participated. All subjects were strongly right handed as reported by questionnaire. A surface electromyograph (EMG) was recorded bilaterally from digastrics and jaw movement detected by an accelerometer attached to a lower incisor. Focal transcranial magnetic stimulation (TMS) was used to assess corticomotor excitability of the digastric representation in M1 of both hemispheres during four tasks: 1) static isometric contraction of digastrics; 2) speaking a single word; 3) visually guided, nonspeech jaw movement that matched the jaw kinematics recorded during task 2; and 4) reciting a sentence. Background EMG was well matched in all tasks and jaw kinematics were similar around the time of the TMS pulse for tasks 2-4. TMS resting thresholds and digastric muscle-evoked potential (MEP) size during isometric contraction did not differ for TMS over left versus right M1. MEPs elicited by TMS over left, but not right M1 increased in size during speech and nonspeech jaw movement compared with isometric contraction. We conclude that left corticobulbar M1 is preferentially engaged for descending control of digastric muscles during speech and the performance of a rapid jaw movement to match a target kinematic profile.

Motor training decreases finger tremor and movement response time in a visuomotor tracking task.

The authors sought to determine whether repeated practice of a skilled motor task reduced the tremor arising from pulsatile control that occurs during and after training. Participants flexed and extended their index finger at the metacarpophalangeal joint to track a screen cursor during skill training, in 6 training runs, each of 3-min duration. Nonskill training comprised voluntary flexion and extension movements. The authors measured performance by the average tracking error in a standard 10-s target pattern embedded in the training runs. Cross-correlation of the motor performance and the target pattern revealed that the improved ability to match the shape of the target pattern accounted for 63% of the improved motor performance and that the decreased time to respond to changes in the target line accounted for 10% of the improvement. Skill, but not nonskill training, reduced tremor after 3 min of training during the training movements and during movements 10 and 25 min afterwards. The authors observed no changes in resting tremor after either training protocol. Although training reduced the tremor, this reduction in itself did not significantly improve tracking performance. The authors conclude that visuomotor skill training produces a general reduction in finger tremor (pulsatile control) during voluntary movements that extends beyond the period of training.

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 GABA(B)-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 GABA(B)-dependent intracortical inhibitory systems are influenced by time of day and modified by circulating levels of cortisol.

Transcranial magnetic stimulation reduces masseter motoneuron pool excitability throughout the cortical silent period.

OBJECTIVE: To evaluate the time-course of changes in masseter motoneuron pool excitability following transcranial magnetic stimulation of motor cortex, and relate this to the duration of the masseter cortical silent period (CSP). METHODS: Surface EMG was recorded bilaterally from masseter and digastric muscles in 13 subjects. Focal TMS was applied at 1.3x active motor threshold (AMT) to motor cortex of one hemisphere to elicit a muscle evoked potential (MEP) and silent period bilaterally in masseter as subjects maintained an isometric bite at approximately 10% maximum. With jaw muscles relaxed, a servo-controlled stretcher evoked a stretch reflex in masseter which was conditioned by TMS (1.3x AMT) at 14 different conditioning-testing intervals. There were 20 trials at each interval, in random order. TMS evoked no MEP in resting masseter, but often produced a small MEP in digastric. RESULTS: Mean (+/-SE) masseter CSP was 67+/-3ms. The masseter stretch reflex was facilitated when stretch preceded TMS by 8 and 10ms, which we attribute to spatial summation of corticobulbar and Ia-afferent excitatory inputs to masseter. Masseter stretch reflex amplitude was reduced when TMS was given up to 75ms before stretch, and for up to 2ms afterwards. CONCLUSIONS: We conclude that descending corticobulbar activity evoked by TMS acts bilaterally on brainstem interneurons that either inhibit masseter motoneurons or increase pre-synaptic inhibition of Ia-afferent terminals for up to 75ms after TMS. The reduction of masseter motoneuron pool excitability following TMS has a similar time-course to the CSP. SIGNIFICANCE: In contrast to the situation for spinal and facial (CN VII) muscles, the masseter CSP appears to have no component that can be attributed exclusively to cortical mechanisms. Abnormalities in the masseter cortical silent period observed in neurological conditions may be due to pathophysiological changes at cortical and/or sub-cortical levels.

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.

Focal transcranial magnetic stimulation of motor cortex evokes bilateral and symmetrical silent periods in human masseter muscles.

OBJECTIVE: To determine whether a single hemisphere exerts distinct inhibitory influences over masseter muscles on each side, and to compare features of the masseter cortical silent period (CSP) evoked by transcranial magnetic stimulation (TMS) with previous reports from limb and other cranial muscles. METHODS: Focal TMS was applied over the motor cortex jaw area in 14 normal subjects. In one experiment, TMS intensity was constant (1.1 or 1.3x active motor threshold, T) and masseter muscle activation varied from 10% to 100% of maximal. In another experiment, muscle activation was constant (20% maximal) and TMS intensity varied from 0.7 to 1.3T. RESULTS: In all subjects, TMS evoked a silent period of similar duration in masseter muscles on both sides. Masseter CSP duration increased at higher TMS intensities, but was not affected by muscle activation level or the size of the excitatory response evoked by TMS. Weak TMS produced a bilateral CSP without short-latency excitation. The masseter CSP was short ( approximately 100ms at 1.3T), yet this was not due to maintenance of excitatory drive from the unstimulated hemisphere, as the masseter CSP was not prolonged with dual-hemisphere TMS. CONCLUSIONS: Intracortical inhibitory circuits activated by TMS have a relatively weak effect on corticotrigeminal neurons supplying masseter, and effects are equivalent for corticobulbar efferents directed to contralateral and ipsilateral masseter motoneuron pools. SIGNIFICANCE: Trigeminally innervated masseter muscles exhibit weak, bilaterally symmetric inhibition following focal TMS. This method can be used to investigate abnormalities of intracortical inhibition in movement disorders or focal lesions affecting the masticatory muscles in humans.

Intracortical inhibition in the human trigeminal motor system.

OBJECTIVE: To investigate the presence and features of short-interval intracortical inhibition (SICI) in the human trigeminal motor system. METHODS: Surface electromyogram (EMG) was recorded from left and right digastric muscles in 7 subjects, along with additional experiments with intramuscular EMG in 2 subjects. Focal transcranial magnetic stimulation (TMS) was used to activate the motor cortex of one hemisphere and elicit motor evoked potentials (MEPs) in digastric muscles on each side, at rest and while subjects activated the muscles at 10% maximal EMG. Paired or single TMS pulses were delivered in blocks of trials, while conditioning TMS intensity and interstimulus interval (ISI) were varied. RESULTS: At rest, paired TMS (3-ms ISI) with conditioning intensities 0.8-0.9x active motor threshold (TA) reduced the digastric MEP amplitude to a similar extent bilaterally. Conditioning at 0.5-0.7TA did not significantly reduce the MEP. MEP amplitude was reduced to a similar extent in both digastric muscles by ISIs between 1 and 4 ms (0.8TA). Voluntary bilateral activation of digastric muscles reduced the effectiveness of conditioning TMS compared to the resting state, with no differences between sides. The similarity of the responses in both digastric muscles was not due to EMG cross-talk (estimated to be approximately 10% in surface records and approximately 2% in intramuscular records), as the intramuscular records showed the same pattern as the surface records. CONCLUSIONS: The effects of paired-pulse TMS on digastric are similar to those reported for contralateral hand muscles, and are consistent with activation of SICI circuits in M1 by conditioning TMS. Our evidence further suggests that the corticomotor representations of left and right digastric muscles in M1 of a single hemisphere receive analogous inhibitory modulation from SICI circuits. SIGNIFICANCE: SICI has been demonstrated in the face area of motor cortex controlling the trigeminal motor system in normal subjects. This method can be used to investigate abnormalities of SICI in movement disorders affecting the masticatory muscles in humans.

Factors influencing the magnitude and reproducibility of corticomotor excitability changes induced by paired associative stimulation.

Several paired-associative stimulation (PAS) protocols induce neuroplastic changes in human motor cortex (M1). To understand better the inherent variability of responses to PAS, we investigated the effectiveness and reproducibility of two PAS paradigms, and neurophysiological and experimental variables that may influence this. Motor evoked potentials (MEPs) were elicited by transcranial magnetic stimulation (TMS) of right M1, and recorded from surface EMG of left abductor pollicis brevis (APB) and first dorsal interosseous before and after PAS. PAS consisted of electrical stimulation of left median nerve paired with TMS over right M1 25 ms later. Twenty subjects were given one of two PAS protocols: short (132 paired stimuli at 0.2 Hz) or long (90 paired stimuli at 0.05 Hz), and were re-tested with the same protocol on 3 separate occasions, with 11 subjects tested in the morning and 9 in the afternoon. Neurophysiological variables assessed included MEP amplitude, resting and active motor threshold, short-interval intracortical inhibition, intracortical facilitation and cortical silent period duration. The short PAS protocol produced greater APB MEP facilitation (51%) than the long protocol (11%), and this did not differ between sessions. The neurophysiological variables did not consistently predict responses to PAS. Both PAS protocols induced more APB MEP facilitation, and greater reproducibility between sessions, in experiments conducted in the afternoon. The mechanism for this is unclear, but circadian rhythms in hormones and neuromodulators known to influence neuroplasticity warrant investigation. Future studies involving PAS should be conducted at a fixed time of day, preferably in the afternoon, to maximise neuroplasticity and reduce variability.

Progressive suppression of intracortical inhibition during graded isometric contraction of a hand muscle is not influenced by hand preference.

GABAergic intracortical inhibition (ICI) in human motor cortex (M1) assists fractionated activation of muscles, and it has been suggested that hemispheric differences in ICI may contribute to hand preference. Previous studies of this issue have all been conducted at rest, with conflicting results. Testing during voluntary activation may reveal functionally relevant differences. In normal subjects, we assessed (1) operation of ICI circuits during selective activation of an intrinsic hand muscle at different forces, and (2) whether this differs between right and left hemispheres. Surface EMG was recorded bilaterally from abductor pollicis brevis (APB), first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles in eleven right-handed subjects. A circular coil applied paired transcranial magnetic stimulation (TMS) with posteriorly directed current in the brain. Conditioning intensity was 0.8 x active threshold and interstimulus interval was 3 ms. TMS was applied to right or left M1 while subjects were at rest or performing isometric thumb abduction at different forces (0.5, 1, 2, 3, 5 and 10 N) with the contralateral hand. Conditioning TMS was less effective at suppressing the muscle evoked potential in APB during 2-10 N thumb abduction (P < 0.0001) versus rest, but not with lower target forces (0.5, 1 N). Conditioning TMS was less effective for FDI and ADM only during 10 N thumb abduction. We conclude that differential modulation of ICI in M1 during selective muscle activation is a function of target isometric force level. At low forces (<5% MVC), ICI is not modulated for the corticospinal neurons controlling the active or inactive muscles. There is a progressive reduction of ICI effects on corticospinal neurons at higher forces, which is largely restricted to corticospinal neurons controlling the muscle targeted for activation over the range of forces tested (up to approximately 25% MVC). The pattern of ICI modulation with selective voluntary muscle contraction was similar in left and right hemispheres during this relatively simple static task. If hemispheric differences in operation of M1 ICI circuits contribute to hand preference, a more challenging finger movement protocol may be needed to demonstrate this asymmetry.

Does motoneuron adaptation contribute to muscle fatigue?

To help reduce the gap between the cellular physiology of motoneurons (MNs) as studied "bottom-up" in animal preparations and the "top-down" study of the firing patterns of human motor units (MUs), this article addresses the question of whether motoneuron adaptation contributes to muscle fatigue. Findings are reviewed on the intracellularly recorded electrophysiology of spinal MNs as studied in vivo and in vitro using animal preparations, and the extracellularly recorded discharge of MUs as studied in conscious humans. The latter "top-down" approach, combined with kinetic measurements, has provided most of what is currently known about the neurobiology of muscle fatigue, including its task and context dependencies. It is argued that although the question addressed is still open, it should now be possible to design new "bottom-up" research paradigms using animal preparations that take advantage of what has been learned with the use of relatively noninvasive quantitative procedures in conscious humans.

Insights into the bilateral cortical control of human masticatory muscles revealed by transcranial magnetic stimulation.

In this brief review I describe details of the functional organisation of the bilateral corticobulbar projections to the trigeminally innervated masticatory muscles, as revealed by transcranial magnetic stimulation of the human brain. The motor cortices of both hemispheres are involved in control of trigeminal motoneurons, however the contralateral hemisphere has the greater excitatory influence. Corticomotoneuronal cells in each hemisphere project to jaw-closer and jaw-opener motoneurons. Less is known about cortically mediated inhibitory effects in the trigeminal motor system, but the available evidence suggests that drive to jaw muscles on each side is affected similarly by intracortical inhibitory processes activated in one hemisphere. Functional studies reveal that the two hemispheres play distinct roles in control of ipsilateral and contralateral muscles, particularly for jaw-closers. Masseter and digastric motor units recruited during low-force contractions do not receive uniform inputs from each hemisphere; the majority of masseter motor units are excited only from the contralateral hemisphere, and while digastric motor units are usually excited from both hemispheres the direct CM cell influence appears to be augmented on the contralateral side by corticobulbar activation of segmental excitatory interneurons. Differences in bilateral cortical control of jaw-closer and jaw-opener muscles may contribute to the more independent control of jaw-closers on each side during functional tasks. Corticobulbar control of the trigeminal muscles during natural tasks such as chewing and speech remains to be investigated with TMS.

Organisation of common inputs to motoneuron pools of human masticatory muscles.

OBJECTIVE: To determine the pattern of organization of common inputs to the motoneuron pools of individual muscles in the masticatory system. METHODS: Six subjects bit on a rubber-coated wooden splint placed between the upper and lower incisor teeth. We recorded the surface electromyogram (EMG) of co-contracting masseter, temporalis and digastric muscles bilaterally during isometric jaw closing at 5%, 10%, 20% and 40% of maximal voluntary masseter EMG. RESULTS: The cross-correlograms of the EMGs of homologous muscle pairs indicate that there are common synaptic inputs to the motoneuron pools of the left and right masseter, and left and right digastric muscles, but not to left and right temporalis. The amplitude of the central peak in masseter and digastric correlograms increased with bite force. When the activity of ipsilateral muscle pairs was cross-correlated, central peaks were prominent for masseter-digastric and masseter-temporalis muscle pairs, and the peak amplitudes increased significantly with bite force. In contrast, no significant central peak was observed for temporalis-digastric muscle pairs at any level of voluntary biting. CONCLUSIONS: We conclude that there is synchronous modulation of input bilaterally to the masseter muscles and to the digastric muscles but not to the temporalis muscles. There is synchronous modulation of input to ipsilateral masseter-digastric and masseter-temporalis muscle pairs but not to temporalis and digastric muscles. SIGNIFICANCE: The extent of common input to motoneuron pools of muscles acting around a common joint varies for different muscle pairs, and is not simply a function of whether the muscles of the pair are synergists or antagonists.

Interhemispheric coupling of corticospinal excitability is suppressed during voluntary muscle activation.

Motor-evoked potentials (MEPs) after transcranial magnetic stimulation (TMS) show a trial-to-trial variation in size at rest that is positively correlated for muscles of the same, and opposite, upper limbs. To investigate the mechanisms responsible for this we have examined the effect of voluntary activation on the correlated fluctuations of MEP size. In 8 subjects TMS was concurrently applied to the motor cortex of each hemisphere using 2 figure-8 coils. MEPs (n = 50) were recorded from left and right first dorsal interosseous (FDI), abductor digiti minimi (ADM), and extensor digitorum communis. At rest, MEPs were significantly positively correlated for pairs of muscles of the same (75% of comparisons) and opposite limb (56% of comparisons). The correlation for within-limb muscle pairs was strongest for FDI and ADM. In contrast, between-limb MEP correlations showed no somatotopic organization. Voluntary activation reduced the strength of MEP correlations between limbs, even for muscle pairs that remained at rest while a remote upper limb muscle was active. In contrast, activation of a remote muscle did not affect the strength of MEP correlation for muscle pairs within the same limb that remained at rest. For within-limb comparisons, activation of one or both muscles of a pair reduced the strength of the MEP correlation, but to a lesser extent than for between-limb pairs. It is concluded that the process linking corticospinal excitability in the two hemispheres is suppressed during voluntary activation, and that different processes contribute to common fluctuations in MEP size for muscles within the same limb.