Simon F. Farmer

Synchronization between motor cortex and spinal motoneuronal pool during the performance of a maintained motor task in man.

1. Simultaneous recordings of cortical activity, recorded as the magnetoencephalogram (MEG), and the electromyogram (EMG) of the ipsilateral and contralateral first dorsal interosseous muscles (1DI) were made during maintained voluntary contractions. 2. The MEG recorded from a localized region of the sensorimotor cortex of the dominant hemisphere was coherent with the EMG from the contralateral 1DI muscle over a limited band of frequencies. The peak coherence was confined largely within the beta range of cortical activity (13‐35 Hz). Significant cortical activity at 10 Hz and 40‐50 Hz was not correlated with motor output. The MEG and EMG from the ipsilateral 1DI muscle were uncorrelated at all frequencies. 3. Significant coherence between the MEG and the EMG was associated with synchronous behaviour between the MEG and EMG in the time domain. 4. The results demonstrate that synchronized cortical activity contributing to MEG activity within the beta range of frequencies during maintained voluntary contractions is coupled to motor output at frequencies of motor‐unit activity associated with motor‐unit synchronization. This observation provides further evidence for the involvement of cortical neurones in the generation of motor‐unit synchronization. 5. We suggest that the coherence between MEG and contralateral EMG observed during maintained isometric contractions may provide an example of binding within the motor system.

The frequency content of common synaptic inputs to motoneurones studied during voluntary isometric contraction in man.

1. The discharges of pairs of individual motor units were recorded from intrinsic hand muscles in man. Single motor unit recordings were obtained either when both members of the motor unit pair were within first dorsal interosseous muscle (1DI:1DI recordings) or where one motor unit was within 1DI and the other in second dorsal interosseous muscle (1DI:2DI recordings). The pairs of motor unit spike trains were cross‐correlated in the time domain and the results compared to those of coherence analysis performed on the same spike train data. Central peaks were present in the cross‐intensity functions, indicating the presence of common synaptic input to the motoneurone pair. Coherence analysis of these data indicated significant association between motor unit firing in the frequency ranges 1‐12 and 16‐32 Hz. 2. Analysis of sequential non‐overlapping segments of data recorded from individual motor unit pairs, demonstrated that both the central cross‐intensity peak and coherence in the frequency bands 1‐12 and 16‐32 Hz were consistent features throughout a long recording. In these sequential recordings, the size of the central cross‐intensity peak and the maximal value of coherence in the frequency band 16‐32 Hz covaried from segment to segment. Analysis of the entire population of motor unit pairs confirmed a positive relationship between the magnitude of peak coherence and the size of the central cross‐intensity peak. 3. Voluntary sinusoidal co‐modulation of the firing rates of pairs of individual motor units recorded from within 1DI was found to produce significant values of coherence corresponding to the frequency of the common modulation. However, firing rate co‐modulation was not found to affect either the size of the central cross‐intensity peak or the maximum value of coherence in the frequency band 16‐32 Hz. 4. Pairs of single motor units were recorded from within 1DI and biceps brachii muscles of healthy subjects. The number and size of the central cross‐intensity peaks and coherence peaks detected were compared for the two muscles. The incidence and size of central cross‐intensity peaks and the incidence and magnitude of 16‐32 Hz coherence peaks were both found to be greater for 1DI recordings when compared to biceps brachii recordings. 5. Single motor unit recordings were made from the intrinsic hand muscles of a patient with severe peripheral deafferentation. Time‐ and frequency‐domain analysis of these recordings revealed cross‐intensity peaks and frequency bands of coherence similar to those seen in healthy subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

Using electroencephalography to study functional coupling between cortical activity and electromyograms during voluntary contractions in humans

Previous studies of neuronal oscillations in sensorimotor cortex in humans and primates have observed rhythmic 15-30 Hz activity, which is correlated with motor output. In humans, this work has been limited to magnetic recordings. In the present study we investigate if similar results can be obtained using electroencephalography (EEG). EEG recordings were made from over the sensorimotor cortex of five adult subjects who performed repeated periods of maintained wrist extension and flexion. Coherence analysis between EEG and electromyogram (EMG) recordings from these muscles revealed correlation in the 15-30 Hz range, with a synchronous correlation structure which matches that previously observed in humans and in paired cortical recordings from primates. We conclude that EEG is equally efficient at investigating functional aspects of these cortical rhythms during voluntary movement in humans.

The effects of physical and semantic incongruities on auditory event-related potentials

Twenty subjects listened to a series of simple sentences, spoken by a male voice, in which the last word was on occasions either made semantically incongruous or was unexpectedly spoken by a female voice. Averages of ERPs to the last words revealed that a consistent late negative component (N456) was associated with semantic incongruity and a late positive component (P416) with physical (voice) incongruity. The results were consistent with those in the visual modality by Kutas and Hillyard (1980a,b) and are interpreted in terms of the facilitatory and inhibitory effects of contextual priming on the processing of the words concerned. In a subsidiary experiment 6 subjects were required to repeat the last words of the same set of sentences as rapidly as possible. Verbal response latency increased by 62 msec to physically incongruous words and by 185 msec to semantically incongruous words.

Rhythmicity, synchronization and binding in human and primate motor systems

This review focuses on recent advances in our understanding of temporal pattern coding in the motor systems of animals and man. Examples of millisecond time scale rhythmic synchronization in the visual system are considered. Results of experiments that demonstrate similar phenomena in the motor system are discussed. Finally problems concerning the nature of the correlation between neurophysiological signals and the relationship of correlation to motor behaviour are explored.

Plasticity of central motor pathways in children with hemiplegic cerebral palsy

To obtain neurophysiologic evidence for a reorganization of central motor pathways in children who had suffered a cerebral lesion at birth, we performed cross-correlation analyses of multiunit EMG recordings obtained from children with hemiplegic cerebral palsy and marked mirror movements. We found that the motoneuron pools of homologous left and right hand muscles received common synaptic input from abnormally branched presynaptic axons. The results of electromagnetic brain stimulation, cutaneomuscular, and tendon reflex testing suggested that these common inputs are provided by abnormally branched corticospinal tract fibers whose origin is the undamaged motor cortex.

Randomised trial of oral and intravenous methylprednisolone in acute relapses of multiple sclerosis.

BACKGROUND An intravenous rather than oral course of methylprednisolone is often prescribed for treating acute relapses in multiple sclerosis (MS) despite the lack of evidence to support this route of administration. Our double-blind placebo-controlled randomised trial was designed to compare the efficacy of commonly used intravenous and oral steroid regimens in promoting recovery from acute relapses in MS. METHODS 42 patients with clinically definite relapse in MS received oral, and 38 intravenous, methylprednisolone. Clinical measurements at entry and at 1 week, 4 weeks, 12 weeks, and 24 weeks included Kurtzkes expanded disability status scale (EDSS), Hausers Ambulatory Index, and an arm-function index. The primary outcome criterion was a difference between the two treatment groups of one or more EDSS grades at 4 weeks. FINDINGS There were no significant differences between the two groups at any stage of the study in any measurement taken: the mean difference in EDSS at 4 weeks (adjusted for baseline level) was 0.07 grades more in those taking oral steroids (95% CI -0.46 to 0.60). The most optimistic outcome for intravenous therapy is an average benefit of less than half a grade improvement on EDSS over oral treatment. INTERPRETATION Since our study did not show any clear advantage of the intravenous regime we conclude that it is preferable to prescribe oral rather than intravenous steroids for acute relapses in MS for reasons of patient convenience, safety, and cost.

Mirror movements studied in a patient with Klippel-Feil syndrome.

1. Electromyographic (EMG) recordings have been made from upper limb muscles in a patient with well‐defined congenital mirror movements occurring in association with Klippel‐Feil syndrome and the results compared to those obtained in normal control subjects. 2. In the patient, liminal percutaneous electrical or magnetic brain stimulation applied over either hemisphere elicited bilateral and symmetrical short‐latency muscle responses in relaxed intrinsic hand muscles. In the normal subjects unilateral brain stimulation only elicited contralateral muscle responses. 3. F response and H reflex studies for the patients ulnar‐supplied intrinsic hand muscles were normal. No crossed responses were recorded in the homologous muscles of the contralateral hand. 4. Scalp‐recorded somatosensory‐evoked responses following ulnar or median nerve stimulation were of normal latency and distribution in the patient. 5. In the patient, cross‐correlation analysis of on‐going single and multiunit needle EMGs recorded between muscles of left and right hands revealed a central peak in the cross‐correlogram. No cross‐correlogram peaks were found between left‐ and right‐hand muscles in normal subjects. The magnitude and time course of the central peaks in the cross‐correlograms constructed between the firing of motor units on opposite sides of the body in the patient were similar to those found in cross‐correlograms constructed between the firing of motor units from muscles on the same side of the body in the patient and in normal subjects. 6. The magnitude of cross‐correlogram peaks detected within a muscle and those detected between left and right homologous muscles showed a gradient in which the largest peaks were found in the intrinsic hand and forearm extensor muscles. The smallest peaks were observed in the forearm flexor muscles. No peaks were detected between left and right biceps brachii muscles. In intrinsic hand muscles, the size of the cross‐correlogram peak detected between the EMGs of homologous muscle pairs was greater than that found for non‐homologous muscle pairs. 7. Cutaneous reflex responses were recorded from first dorsal interosseous muscle following unilateral electrical stimulation of the digital nerves of the index finger. In the patient, this produced an early excitatory (E1) response on the stimulated side. Later excitatory (E2 and E3) responses, of approximately equal size and latency, were distributed bilaterally. In the normal subjects, reflex responses were confined to the stimulated side.(ABSTRACT TRUNCATED AT 400 WORDS)

Central nervous pathways underlying synchronization of human motor unit firing studied during voluntary contractions.

1. Motor unit firing has been studied during weak voluntary isometric contractions with pairs of needle electrodes in normal human subjects. 2. Pre‐ and post‐stimulus time histograms of the firing time of firing of one event unit before and after the time of firing of another reference (stimulus) unit showed a clear central peak, indicative of synchronization. 3. Synchronization was seen in all the muscles studied. The mean strength of synchronization, expressed as the number of concomitant discharges of the two units as a proportion of the number of stimulus unit discharges, was 0.095 extra event unit spikes/reference unit spike (range 0.042‐0.28) for first dorsal interosseous muscle, 0.016 extra event unit spikes per reference unit spike (range 0‐0.043) for medial gastrocnemius and 0.056 extra event unit spikes per reference unit spike range 0.016‐0.079) for tibialis anterior. 4. The mean duration of synchronization was 11.3 ms (range 5.0‐21.0 ms) for first dorsal interosseous, 10.3 ms (range 3.5‐21.7 ms) for medial gastrocnemious and 13.5 ms (range 3.0‐25.0) for tibialis anterior. 5. Seven patients with radiographically and clinically identified central strokes were studied while they made weak voluntary isometric contractions. The duration of synchronization was significantly prolonged compared to that found in normal subjects. In these stroke patients the mean duration of synchronization on the affected side was longer than that seen in the normal subjects, and in first dorsal interosseous muscle was 35.4 ms (range 12.0‐65.0 ms), in medial gastrocnemius was 21.3 ms (range 4.0‐43.0 ms) and in tibialis anterior was 28.8 ms (range 14.0‐49.0 ms). 6. The mean strength of synchronization of motor unit discharge was found to be greater in the stroke patients than that seen in the normal subjects for first dorsal interosseous muscle (0.161 extra event unit spikes per reference unit spike, range 0.017‐0.391) and for medial gastrocnemius (0.030 extra event unit spikes per reference unit spike) but only significantly so when pooled data was compared. There was no difference in the strength of motor unit synchronization in tibialis anterior between stroke patients and normal subjects. 7. Broad duration synchronization among first dorsal interosseous motor units was also found in a patient with a rostral cervical spine lesion (total duration range 43‐46 ms; n = 2), but not in a patient with a caudal (thoracic) spinal lesion.(ABSTRACT TRUNCATED AT 400 WORDS)

A review of recent applications of cross-correlation methodologies to human motor unit recording

This article reviews some recent applications of time and frequency domain cross-correlation techniques to human motor unit recording. These techniques may be used to examine the pre-synaptic mechanisms involved in control of motoneuron activity during on-going motor tasks in man without the need for imposed and artificial perturbations of the system. In this review we examine, through several examples, areas in which insights have been gained into the basic neurophysiological processes that bring about motoneuron firing in man and illustrate how these processes are affected by central nervous system pathology. We will demonstrate that synchronization and coherence may be revealed between human motor unit discharges and give examples that support the hypothesis that these phenomena are generated by activity in a focused common corticospinal input to spinal motoneurons. Disruption of central motor pathways due to diseases of the nervous system leads to pathophysiological alterations in the activity of these pre-synaptic motoneuron inputs that can be revealed by cross-correlation analysis of motor unit discharges. The significance of these studies and outstanding questions in this field are discussed.