AAEM minimonograph #3: motor unit recruitment.

Motor unit recruitment is the process by which different motor units are activated to produce a given level and type of muscle contraction. At minimal levels of muscle contraction (innervation), muscle force is graded by changes in firing rate (rate coding) of individual motoneurons (MNs). At higher levels of innervation, recruitment is accomplished by the addition of different motor units firing at or above physiologic tremor rate. During slowly graded and ballistic increases in force, motor units are recruited in rank order of their size. In addition to MN soma diameter, other factors contribute to the selectivity of MN activation. For la afferent MN activation in the cat, synaptic density and efficacy as well as specific membrane resistance are also rank ordered for slow, fatigue resistant, and fast fatigue motor units with slow motor units recruited first. The central drive for motor unit activation is distributed to all the MNs of the pool serving a given muscle. Size-structure organization of the MN pool determines the order of recruitment and how MNs interact with each other. Disorders of the motor unit affect recruitment. A method for the clinical electromyographic assessment of recruitment is suggested. Assessment is made at three levels of innervation: minimal contraction for onset and recruitment firing rates; moderate contraction required to maintain the limb against gravity for the maximum number of motor units, their firing rates, and motor unit spikes/s; maximal voluntary contraction (MVC) for detection of high threshold enlarged motor units characteristic of reinnervation and completeness of the interference pattern (IP). Loss of muscle fibers results in early and excessive recruitment at minimal and moderate levels of innervation. Loss of motor units can result in both an increased rate and range of single motor unit firing at all levels of innervation. With reinnervation and enlargement of motor units, firing rates increase significantly and the interference pattern during MVC is incomplete.     

Cortical mechanisms mediating the inhibitory period after magnetic stimulation of the facial motor area

We studied the silent period (SP) that interrupts voluntary electromyographic activity (EMG) in facial muscles, after transcranial magnetic stimulation (TMS), in normal subjects. High-intensity magnetic stimulation with a 12-cm round coil centered at the vertex induced a long-lasting SP (215 ms), whereas supramaximal stimulation of the facial nerve only induced a short (< 20 ms) and incomplete EMG suppression, and cutaneous stimuli had no inhibitory effect at all. Cutaneous trigeminal stimulation delivered after TMS evoked blink-like reflexes, showing that facial motoneurons were not inhibited during the SP. Simultaneous recordings from perioral muscles (large cortical representation) and from orbicularis oculi and masseter muscles (small cortical representation) showed SPs of identical duration. Focal stimuli with a figure-of-eight coil showed that positioning of the coil was critical and that the optimal scalp sites for evoking the largest motor potentials and longest SPs coincided. Low-intensity stimulation occasionally elicited short SPs without a preceding motor potential. We conclude that the SP induced in facial muscles by TMS results from the excitation of cortical inhibitory interneurons surrounding the upper motoneurons. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 418–424, 1997.     

Motor unit firing behavior in slow and fast contractions of the first dorsal interosseous muscle of healthy men

The motor unit recruitment threshold and firing rate were evaluated during slow and fast contraction of the first dorsal interosseous (FDI) muscle by healthy young men. Using a special quadrifilar electrode myoelectric activity was recorded during voluntary isometric contraction. Motor unit action potentials (MUAPs) were decomposed into individual MUAP trains by the electromyography (EMG) signal decomposition technique. Recruitment thresholds of the motor units decreased with the increase in the speed of contraction, and there was no recruitment reversal despite the increase. In terms of rate coding, the firing rates of the motor units increased as the speed of contraction increased; however, a high threshold motor unit always had a lower firing rate than a low threshold motor unit regardless of the contraction speed.At all contraction speeds, recruitment and rate coding may act through the same mechanism. If excitation of the motoneuron pool occurs rather than excitation of an individual motoneuron, a low threshold motor unit is easier to recruit and fire repetitively than a high threshold one. The motor unit firing behavior during fast contraction basically may be the same as during slow contraction.     

Motor inhibition and excitation are independent effects of magnetic cortical stimulation.

We administered magnetic cortical stimulation (MCS) during voluntary contraction of intrinsic hand muscles to 8 patients with motor neuron disease (MND), 5 patients with pure lower motor neuron syndromes (LMN), a patient with severe subacute sensory neuropathy (SSN), and 10 healthy volunteers. Patients with MND had clinical evidence of upper MND and elevated thresholds for (3 patients) or absence of (5 patients) motor evoked potentials (MEPs). MCS during sustained contraction inhibited electromyographic activity in 6 of 8 patients with MND, without preceding MEPs. MCS had no effect on the electromyogram (EMG) of the other 2 patients with MND. In normal subjects and patients with LMN, inhibition of EMG was never seen without a preceding MEP, regardless of stimulus intensity. In the patient with SSN, MCS elicited normal MEPs and inhibited the EMG in a pattern similar to normal subjects, whereas supramaximal electrical stimulation of median and ulnar nerves failed to inhibit the EMG despite normal M and F responses. Our findings indicate that the inhibitory effects of MCS on EMG are not dependent solely on changes in afferent feedback caused by the muscle twitch produced by the MEP, or on Renshaw cell inhibition. We suggest that some of the inhibitory and excitatory effects of MCS on the motor system are mediated by distinct cortical elements, which may have different susceptibilities to pathophysiological processes in MND.     

Analysis of double discharges in amyotrophic lateral sclerosis

Double discharges of motor units (MUs) occurring during sustained voluntary muscle contractions are observed occasionally in healthy muscles and more frequently in disorders of the neuromuscular system. In healthy subjects, double discharges are generated in motoneurons (MNs) and are considered to be a sign of their increased excitability. Therefore, an analysis of their firing pattern may provide information on the state of MNs in neuromuscular diseases, particularly in amyotrophic lateral sclerosis (ALS), whose etiology remains to be disclosed. Firing patterns of MUs capable of firing double discharges were analyzed in brachial biceps of 14 patients with ALS (184 MUs) and 8 healthy control subjects (102 MUs). The incidence of MUs capable of firing double discharges was significantly higher in ALS patients (28.8%) than in controls (3.9%). The majority of doublet interval durations (range 4-8 ms) as well as firing patterns of doubling MUs did not differ between subject groups. Although our data confirm the hyperexcitability of the MN pool in ALS, analysis of firing characteristics of doubling MUs indicates that doublet generation is governed by the same mechanism as in controls, that is, by delayed depolarization. Our findings may provide insight into MN function in ALS.     

Neural noise and cortical inhibition in schizophrenia

BackgroundNeural information processing is subject to noise and this leads to variability in neural firing and behavior. Schizophrenia has been associated with both more variable motor control and impaired cortical inhibition, which is crucial for excitatory/inhibitory balance in neural commands.HypothesisIn this study, we hypothesized that impaired intracortical inhibition in motor cortex would contribute to task-related motor noise in schizophrenia.MethodsWe measured variability of force and of electromyographic (EMG) activity in upper limb and hand muscles during a visuomotor grip force-tracking paradigm in patients with schizophrenia (N = 25), in unaffected siblings (N = 17) and in healthy control participants (N = 25). Task-dependent primary motor cortex (M1) excitability and inhibition were assessed using transcranial magnetic stimulation (TMS).ResultsDuring force maintenance patients with schizophrenia showed increased variability in force and EMG, despite similar mean force and EMG magnitudes. Compared to healthy controls, patients with schizophrenia also showed increased M1 excitability and reduced cortical inhibition during grip-force tracking. EMG variability and force variability correlated negatively to cortical inhibition in patients with schizophrenia. EMG variability also correlated positively to negative symptoms. Siblings had similar variability and cortical inhibition compared to controls. Increased EMG and force variability indicate enhanced motor noise in schizophrenia, which relates to reduced motor cortex inhibition.ConclusionThe findings suggest that excessive motor noise in schizophrenia may arise from an imbalance of M1 excitation/inhibition of GABAergic origin. Thus, higher motor noise may provide a useful marker of impaired cortical inhibition in schizophrenia.     

Modulation of single motor unit discharges using magnetic stimulation of the motor cortex in incomplete spinal cord injury

OBJECTIVES: Motor evoked potentials (MEPs) and inhibition of voluntary contraction to transcranial magnetic stimulation (TMS) of the motor cortex have longer latencies than normal in patients with incomplete spinal cord injury (iSCI) when assessed using surface EMG. This study now examines the modulation of single motor unit discharges to TMS with the aim of improving resolution of the excitatory and inhibitory responses seen previously in surface EMG recordings. METHODS: A group of five patients with iSCI (motor level C4-C7) was compared with a group of five healthy control subjects. Single motor unit discharges were recorded with concentric needle electrodes from the first dorsal interosseus muscle during weak voluntary contraction (2%-5% maximum). TMS was applied with a 9 cm circular stimulating coil centred over the vertex. Modulation of single motor unit discharges was assessed using peristimulus time histograms (PSTHs). RESULTS: Mean (SEM) threshold (expressed as percentage of maximum stimulator output (%MSO)) for the excitatory peak (excitation) or inhibitory trough (inhibition) in the PSTHs was higher (p<0.05) in the patients (excitation = 47.1 (5.9) %MSO; inhibition = 44.3 (3.2) %MSO) than in controls (excitation=31.6 (1.2) %MSO; inhibition = 27.4 (1.0) %MSO). Mean latencies of excitation and inhibition were longer (p<0.05) in the patients (excitation=35 (1.8) ms; inhibition = 47.1 (1.8) ms) than in the controls (excitation = 21.1 (1.6) ms; inhibition = 27 (0.4) ms). Furthermore, the latency difference (inhibition-excitation) was longer (p<0.05) in the patients (10.4 (2.1) ms) than in the controls (6.2 (0.6) ms). CONCLUSION: Increased thresholds and latencies of excitation and inhibition may reflect degraded corticospinal transmission in the spinal cord. However, the relatively greater increase in the latency of inhibition compared with excitation in the patients with iSCI may reflect a weak or absent early component of cortical inhibition. Such a change in cortical inhibition may relate to the restoration of useful motor function after iSCI.     

Covariation of corticospinal efficiency and silent period in motoneuron diseases

For a better understanding of the changes affecting the cortically induced silent period (SP) in motoneuron disease, the excitatory and inhibitory effects of transcranial magnetic stimulation were explored repeatedly in 8 patients with amyotrophic lateral sclerosis (ALS), 3 patients with Kennedy's disease (KD), and 10 healthy subjects. In KD, the background electromyogram (EMG) and the motor evoked potential (MEP) area were both enhanced. However, neither the corticospinal efficiency (MEP gain, the ratio between MEP and background EMG) nor the duration of the SP differed from healthy subjects. In ALS patients, the MEP gain and the SP duration decreased conspicuously with time. We conclude that use of the MEP gain improves detection of corticospinal dysfunction in ALS patients. Part of the SP shortening in ALS seems to reflect the reduced activation of cortical or spinal inhibitory networks by the abnormal corticospinal pathway.     

On the estimation of silent period thresholds in transcranial magnetic stimulation

ObjectiveWe evaluated the induction of corticospinal silent period (SP) using transcranial magnetic stimulation (TMS) at stimulation intensities normalized to resting motor threshold (rMT) or silent period thresholds (SPTs). The aim was to reduce the characteristic inter-individual variation in SP measurements in healthy population to improve the sensitivity of such measurements.MethodsThe cortical representation area of the right hand musculature of 12 healthy subjects was stimulated with navigated TMS with varying stimulating intensities. Subsequently, the individual SPTs for eliciting SPs of 20, 30, and 50 ms in duration were determined from the input–output characteristics.ResultsWhile SPT for 20 and 50 ms SPs differed from rMT, the SPT for 30 ms was similar to rMT. Nevertheless, the inter-individual variation in SP duration was reduced significantly at 120% of SPT30 when compared with SP durations obtained at 120% of rMT.ConclusionsInter-individual variation in the SP duration decreases when applying TMS at stimulation intensities normalized to the individual SPTs instead to the rMT. This makes the SP duration more specific to inhibition and less affected by changes in cortical excitability.SignificanceUse of individual SPTs may improve the sensitivity of the SP measures in studies with inter-individual design.     

Relevance of stimulus duration for activation of motor and sensory fibers: implications for the study of H-reflexes and magnetic stimulation.

Electric stimuli with durations of 0.5-1.0 msec are optimal for studies of H-reflexes. It is more difficult to obtain H-reflexes with shorter duration stimuli or with magnetic stimulation. In order to understand this behavior, we studied the excitation thresholds for motor and sensory fibers in the ulnar, median and tibial nerves using both electric and magnetic stimulation. For short duration electrical stimuli (0.1 msec) the threshold for motor fibers is lower than for sensory fibers. For longer duration electric stimuli (1.0 msec) the threshold for sensory fibers is lower. For magnetic stimulation the threshold for motor fibers is much lower than for sensory fibers. Thus, stimulus duration is a critical parameter for sensory fiber excitation, and current magnetic stimulators are not optimal.     

Neurophysiological testing in anorectal disorders

The neurophysiological techniques currently available to evaluate anorectal disorders include concentric needle electromyography (EMG) of the external anal sphincter, anal nerve terminal motor latency (TML) measurement in response to transrectal electrical stimulation or sacral magnetic stimulation, motor evoked potentials (MEPs) of the anal sphincter to transcranial magnetic cortical stimulation, cortical recording of somatosensory evoked potentials (SEPs) to anal nerve stimulation, quantification of electrical or thermal sensory thresholds (QSTs) within the anal canal, sacral anal reflex (SAR) latency measurement in response to pudendal nerve or perianal stimulation, and perianal recording of sympathetic skin responses (SSRs). In most cases, a comprehensive approach using several tests is helpful for diagnosis: needle EMG signs of sphincter denervation or prolonged TML give evidence for anal motor nerve lesion; SEP/QST or SSR abnormalities can suggest sensory or autonomic neuropathy; and in the absence of peripheral nerve disorder, MEPs, SEPs, SSRs, and SARs can assist in demonstrating and localizing spinal or supraspinal disease. Such techniques are complementary to other methods of investigation, such as pelvic floor imaging and anorectal manometry, to establish the diagnosis and guide therapeutic management of neurogenic anorectal disorders.     

Changes in motor cortex excitability during muscle fatigue in amyotrophic lateral sclerosis

To further investigate the pathophysiology of amyotrophic lateral sclerosis (ALS), the silent period (SP) evoked by transcranial magnetic stimulation during a fatiguing muscle contraction was evaluated in 15 patients and in 15 healthy subjects. Physiological lengthening of the SP duration was not observed in patients with disease duration of > or = 2 years. Decreased intracortical inhibition, probably secondary to dysfunction of the inhibitory interneurons that modulate the corticomotoneuronal firing, appears in later stages of disease. Normal motor cortex adaptation is impaired and cortical hyperexcitability might be unmasked during fatigue in ALS patients with longer disease duration.     

The silent period after magnetic brain stimulation in generalized tetanus.

The cortical silent period has not previously been studied in tetanus. Transcranial magnetic brain stimulation in a patient with generalized tetanus revealed enlarged electromyographic (EMG) responses and absence or reduction of the late phase of EMG silence following the motor evoked potential in sternomastoid and biceps brachii muscles. Following clinical recovery, the silent period returned to normal. This observation is interpreted as evidence of impaired inhibitory mechanisms at multiple levels of the nervous system, including the cortex, in generalized tetanus.     

Oculomotor control in calliphorid flies: Head movements during activation and inhibition of neck motor neurons corroborate neuroanatomical predictions

In tethered flying flies, moving contrast gratings or small spots elicit head movements which are suited to track retinal images moving at velocities up to 3,000°/sec (about 50 Hz contrast frequency for gratings of spatial wavelength 15°). To investigate the neural basis of these movements we have combined videomicroscopy with electrophysiological stimulation and recording to demonstrate that excitation of prothoracic motor neurons projecting in the anterodorsal (ADN) and frontal nerves (FN), respectively, generates the yaw and roll head movements measured behaviorally. Electrical stimulation of the ADN produces head yaw. The visual stimuli which excite the two ADN motor neurons (ADN MNs) are horizontal motion of gratings or spots moving clockwise around the yaw axis in the case of the right ADN (counterclockwise for left ADN). Activity is inhibited by motion in the opposite direction. Spatial sensitivity varies in the yaw plane with a maximum between 0° and 40° ipsilaterally, but both excitation and inhibition are elicited out to 80° in the ipsilateral and contralateral fields. ADN MNs respond to contrast frequencies up to 15–20 Hz, with a peak around 2–4 Hz forgrating motion in the excitatory or inhibitory directions. Electrical stimulation of the FN primarily elicits roll down to the ipsilateral side. The one FN MN consistently driven by visual stimulation is excited by downward motion and inhibited by upward motion at 80° azimuth in the ipsilateral visual field. At ?80° contralateral, visual motion has the opposite effect: Upward is excitatory and downward is inhibitory. The FN MN is tuned to contrast frequencies in the same range as the ADN MNs, with peak sensitivity around 4 Hz. The functional organization of inputs to the ADN and FN is discussed with respect to identified visual interneurons and parallel pathways controlling motor output. © 1995 Wiley-Liss, Inc.     

Excitation of the motor cortex associated with the E2 phase of cutaneous reflexes in man

We investigated excitability changes of the motor cortex associated with the E2 phase of cutaneous reflexes in the first dorsal interosseous muscle using transcranial electrical and magnetic stimulation of the motor cortex in humans. EMG responses to combined cutaneous and weak magnetic cortical stimulation, which were elicited during the E2 phase of cutaneous reflexes, were larger than those by the same magnetic cortical stimulation alone. This facilitatory effect was reduced or even inhibitory effect was seen when the intensity of cortical stimulation was increased. Responses to weak electrical cortical stimulation were less affected by the combined cutaneous stimulation. The same facilitatory effect on responses to weak magnetic cortical stimulation was also observed in single motor unit recordings, too. Dissociation between facilitatory effects on the responses evoked by weak magnetic and weak electrical cortical stimulations suggests that the motor cortical excitability is increased in association with the E2 phase. The present results are consistent with the hypothesis that the E2 phase is a kind of transcortical reflex.     

Suppression and long latency excitation of single spinal motoneurons by transcranial magnetic stimulation in health,multiple sclerosis,and stroke

Whether or not suppression at the level of the spinal motoneuron plays a role in motor deficits such as central paresis is unknown. In this study suppression in the firing of tonically active low threshold single motoneurons following low intensity transcranial magnetic stimulation is described in health and disease. Changes in firing probability in the absence of an early excitatory response were studied in a total of 14 motor units from 4 healthy subjects, 5 patients with multiple sclerosis, and 1 patient with stroke. Firing probability began to fall 18–59 ms after the stimulus and remained low for a period of 27–133 ms. There were no obvious differences between the three subject groups. The change in firing probability was not associated with specific physical signs. Late rises in firing probability were seen in 7 of the 14 motor units at latencies that were similar to the secondary peak which is known to occur with higher stimulus intensities. It is argued that the mechanism of partial suppression is not dependent on the full integrity of the pyramidal tract and is likely to involve a transient withdrawal of descending excitatory drive rather than an inhibitory postsynaptic potential at the spinal motoneuron. © 1994 John Wiley & Sons, Inc.     

Shortened silent period produced by magnetic cortical stimulation in patients with Parkinson's disease

Magnetic cortical stimulation can produce silent periods (SP) following excitatory motor responses. In patients with Parkinson's disease (PD), a shorter SP was observed. The shortened SP in PD patients improved after levodopa administration. This shortened SP in PD patients may be related to the hyperactivity of the motor cortex, and to the dopaminergic system. In control subjects, sound stimulation produced prolongation of the SP at a time interval of 100 ms between sound and magnetic cortical stimulation-increase in the inhibitory function. However, the prolongation of the SP after sound stimulation was not observed in PD patients lack of an increase in the inhibitory function. Even after levodopa administration, sound did not prolong the SP in PD patients. The change of the auditory effects on the SP may be due to the abnormal function of the reticular formation in PD. This change might be independent of the dopaminergic system.     

Properties of spinal motoneurons and interneurons in the adult turtle: Provisional classification by cluster analysis

The purpose of the present study was to compare, in motoneurons (MNs) vs. interneurons (INs), selected passive, transitional, and active (firing) properties, as recorded in slices of lumbosacral spinal cord (SC) taken from the adult turtle. The cells were provisionally classified on the basis of (1) the presence (in selected INs) or absence (MNs and other INs) of spontaneous discharge, (2) a cluster analysis of selected properties of the nonspontaneously firing cells, (3) a comparison to previous data on turtle MNs and INs, and (4) a qualitative comparison of the results with those reported for other vertebrate species (lamprey, cat). The provisional nomenclature accommodated properties appropriate for solely MNs (Main MN group) vs. nonspontaneously firing INs (Main IN-N) vs. spontaneously firing INs (IN-S) and for neurons with two degrees of intermediacy between the Main MN and the Main IN-N groups (Overlap MN, Overlap MN/IN). Morphological reconstructions of additional cells, which had been injected with biocytin during the electrophysiological tests, were shown to provide clear-cut support for the provisional classification procedure. The values for the measured parameters in the 96 tested cells covered the spectrum reported previously across adult vertebrate species and were robust in measurements made on different SC slices up to 5 days after their removal from the host animal. The interspecies comparisons permitted the predictions that (1) our Main MN and Overlap MN cells would be analogous to two MN types that innervate fast-twitch and slow-twitch skeletomotor muscle fibers, respectively, in the cat, and (2) the MNs in our Overlap MN/IN group probably innervate slow (nontwitch, tonic) muscle fibers whose presence has recently been established in the turtle hindlimb. In summary, the results bring out the utility of the SC slice preparation of the turtle for study of spinal motor mechanisms in adult tetrapod vertebrates, particularly as an adjunct to the in vivo cat, because of the ease with which robust measurements can be made of the active properties of both MNs and INs. J. Comp. Neurol. 400:544–570, 1998. © 1998 Wiley-Liss, Inc.     

Rank-ordered regulation of motor units

Myoelectric signals were detected from the tibialis anterior muscle of 5 subjects with a quadrifilar needle electrode while the subjects generated isometric forces that increased linearly with time (10% of maximal voluntary contraction/s) up to maximal voluntary level. Motor unit firing rates were studied as a function of force throughout the full range of muscle force output. The relationship between force and firing rate was found to contain three distinct regions. At recruitment and near maximal force levels, firing rates increased more rapidly with force than in the intermediate region. Furthermore, in the regions with rapid increases, the rate of change of firing rate was correlated to the recruitment threshold, with higher recruitment threshold motor units displaying greater rates of change. In the intermediate region, all motor units had similar rates of change of firing rate. A weak positive correlation was found between initial firing rate and recruitment threshold. Firing rates of motor units at any instant were found to be ordered according to the recruitment order: at any given time in the contraction motor units with lower recruitment thresholds had higher firing rates than units with higher recruitment thresholds. Firing rates of all motor units were observed to converge to the same value at maximal forces. Mechanisms underlying motor unit recruitment and firing rate modulation are discussed in the context of a conceptual model. © 1996 John Wiley & Sons, Inc.     

Inhibition of the human primary motor area by painful heat stimulation of the skin.

OBJECTIVE: To prove whether painful cutaneous stimuli can affect specifically the motor cortex excitability. METHODS: The electromyographic (EMG) responses, recorded from the first dorsal interosseous muscle after either transcranial magnetic or electric anodal stimulation of the primary motor (MI) cortex, was conditioned by both painful and non-painful CO2 laser stimuli delivered on the hand skin. RESULTS: Painful CO2 laser stimuli reduced the amplitude of the EMG responses evoked by the transcranial magnetic stimulation of both the contralateral and ipsilateral MI areas. This inhibitory effect followed the arrival of the nociceptive inputs to cerebral cortex. Instead, the EMG response amplitude was not significantly modified either when it was evoked by the motor cortex anodal stimulation or when non-painful CO2 laser pulses were used as conditioning stimuli. CONCLUSIONS: Since the magnetic stimulation leads to transynaptic activation of pyramidal neurons, while the anodal stimulation activates directly cortico-spinal axons, the differential effect of the noxious stimuli on the EMG responses evoked by the two motor cortex stimulation techniques suggests that the observed inhibitory effect has a cortical origin. The bilateral cortical representation of pain explains why the painful CO2 laser stimuli showed a conditioning effect on MI area of both hemispheres. Non-painful CO2 laser pulses did not produce any effect, thus suggesting that the reduction of the MI excitability was specifically due to the activation of nociceptive afferents.