Biomedical subjects

R N Lemon

Publications and source records attributed to R N Lemon.

At least 19 recordsLinked to original sources

PubMed2006

International spinal research trust research strategy. III: A discussion document.

STUDY DESIGN: Discussion document. OBJECTIVES/METHODS: To review the Research Strategy of the International Spinal Research Trust (ISRT), which identifies key areas of basic and clinical research that are likely to be beneficial in developing potential treatments for spinal cord injury for funding. This strategy is intended to both guide the programme of research towards areas of priority and stimulate discussion of the different avenues of research. This latest document has been developed to take into account the scientific progress in the 6 years since publication of the previous Research Strategy. RESULTS/DISCUSSION: The latest scientific developments in research designed to repair the spinal cord and restore function following injury and how they might impact on spinal cord injury research are highlighted.

Biomedical Research↗

PubMed2005

A cortico-cortical mechanism mediating object-driven grasp in humans.

Humans and other primates demonstrate an exquisite ability to precisely shape their hand when reaching out to grasp an object. Here we used a recently developed transcranial magnetic stimulation paradigm to examine how information about an object's geometric properties is transformed into specific motor programs. Pairs of transcranial magnetic stimulation pulses were delivered at precise intervals to detect changes in the excitability of cortico-cortical inputs to motor cortex when subjects prepared to grasp different objects. We show that at least 600 ms before movement, there is an enhancement in the excitability of these inputs to the corticospinal neurons projecting from motor cortex to the specific muscles that will be used for the grasp. These changes were object- and muscle-specific, and the degree of modulation in the inputs was correlated with the pattern of muscular activity used later by individual subjects to grasp the objects. In a number of control experiments, we demonstrated that no change in excitability was observed during object presentation alone, under conditions in which subjects imagined grasping the object, or before movements involving the same muscles but without an object. This finding demonstrates a cortico-cortical mechanism subserving the transformation from the geometrical properties of an object to the outputs from motor cortex before grasp that is specific for object-driven movements.

Adult↗

PubMed2004

Patterns of muscle activity underlying object-specific grasp by the macaque monkey.

During object grasp, a coordinated activation of distal muscles is required to shape the hand in relation to the physical properties of the object. Despite the fundamental importance of the grasping action, little is known of the muscular activation patterns that allow objects of different sizes and shapes to be grasped. In a study of two adult macaque monkeys, we investigated whether we could distinguish between EMG activation patterns associated with grasp of 12 differently shaped objects, chosen to evoke a wide range of grasping postures. Each object was mounted on a horizontal shuttle held by a weak spring (load force 1-2 N). Objects were located in separate sectors of a "carousel," and inter-trial rotation of the carousel allowed sequential presentation of the objects in pseudorandom order. EMG activity from 10 to 12 digit, hand, and arm muscles was recorded using chronically implanted electrodes. We show that the grasp of different objects was characterized by complex but distinctive patterns of EMG activation. Cluster analysis shows that these object-related EMG patterns were specific and consistent enough to identify the object unequivocally from the EMG recordings alone. EMG-based object identification required a minimum of six EMGs from simultaneously recorded muscles. EMG patterns were consistent across recording sessions in a given monkey but showed some differences between animals. These results identify the specific patterns of activity required to achieve distinct hand postures for grasping, and they open the way to our understanding of how these patterns are generated by the central motor network.

Animals↗

PubMed2004

Coupling of oscillatory activity between muscles is strikingly reduced in a deafferented subject compared with normal controls.

Oscillatory activity in the primate motor cortex has been shown to be phase locked to oscillations in contralateral hand and forearm muscle activity in the 15- to 30-Hz frequency range. Recent studies have shown that the degree of coupling between the cortex and the periphery is strongly influenced by the type and degree of movements of the digits. It has also been suggested that changes in corticomuscular and muscle-muscle coherence could be modulated by peripheral sensory inputs. In the current study, we investigated task-dependent changes in the coherent coupling of electromyographic (EMG) activity recorded from different intrinsic (abductor pollicis brevis and first dorsal interosseous) and two extrinsic (flexor digitorum superficialis and extensor digitorum communis) hand muscles during performance of a precision-grip task by normal subjects and by a single subject who has a total loss of touch, vibration, pressure, and kinesthetic sensation below the neck. The task required a hold-move-hold pattern of grip force to be exerted on a compliant object with the dominant right hand. We found significant task-related modulation of 15- to 30-Hz coherence between EMG activity in hand muscles in the control subjects. In contrast, the deafferented subject showed very low levels of significant coherence in the 15- to 30-Hz range and no peak at this frequency in the power spectra of her EMG activity. These results suggest that the presence of sensory afferent signals are necessary for the modulation of 15- to 30-Hz oscillations in the motor system.

Adult↗

PubMed2004

Macaque ventral premotor cortex exerts powerful facilitation of motor cortex outputs to upper limb motoneurons.

The ventral premotor area (F5) is part of the cortical circuit controlling visuomotor grasp. F5 could influence hand motor function through at least two pathways: corticospinal projections and corticocortical projections to primary motor cortex (M1). We found that stimulation of macaque F5, which by itself evoked little or no detectable corticospinal output, could produce a robust modulation of motor outputs from M1. Arrays of fine microwires were implanted in F5 and M1. During terminal experiments under chloralose anesthesia, single stimuli delivered to M1 electrodes evoked direct (D) and indirect (I1,I2, and I3) corticospinal volleys. In contrast, single F5 shocks were ineffective; double shocks (3 msec separation) evoked small I waves but no D wave. However, when the test (T) M1 shock was conditioned (C) by single or double F5 shocks, there was strong facilitation of I2 and I3 waves from M1, with C-T intervals of <1 msec. Intracellular recordings from 79 arm and hand motoneurons (MNs) revealed no postsynaptic effects from single F5 shocks. In contrast, these stimuli produced a robust facilitation of I2 and I3 EPSPs evoked from M1 (60% of MNs); this was particularly marked in hand muscle MNs (92%). Muscimol injection in M1 reduced I waves from F5 and abolished the F5-induced facilitation of late I waves from M1, and of EPSPs associated with them. Thus, some motor effects evoked from F5 may be mediated by corticocortical inputs to M1 impinging on interneurons generating late corticospinal I waves. Similar mechanisms may allow F5 to modulate grasp-related outputs from M1.

Animals↗

PubMed2004

Effects of transcranial direct current stimulation over the human motor cortex on corticospinal and transcallosal excitability.

Weak transcranial direct current stimulation (tDCS) can induce long lasting changes in cortical excitability. In the present study we asked whether tDCS applied to the left primary motor cortex (M1) also produces aftereffects distant from the site of the stimulating electrodes. We therefore tested corticospinal excitability in the left and the right M1 and transcallosal excitability between the two cortices using transcranial magnetic stimulation (TMS) before and after applying tDCS. Eight healthy subjects received 10 min of anodal or cathodal tDCS (1 mA) to the left M1. We examined the amplitude of contralateral motor evoked potentials (MEPs) and the onset latency and duration of transcallosal inhibition with single pulse TMS. MEPs evoked from the tDCS stimulated (left) M1 were increased by 32% after anodal and decreased by 27% after cathodal tDCS, while transcallosal inhibition evoked from the left M1 remained unchanged. The effect on MEPs evoked from the left M1 lasted longer for cathodal than for anodal tDCS. MEPs evoked from the right M1 were unchanged whilst the duration of transcallosal inhibition evoked from the right M1 was shortened after cathodal tDCS and prolonged after anodal tDCS. The duration of transcallosal inhibition returned to control values before the effect on the MEPs from the left M1 had recovered. These findings are compatible with the idea that tDCS-induced aftereffects in the cortical motor system are limited to the stimulated hemisphere, and that tDCS not only affects corticospinal circuits involved in producing MEPs but also inhibitory interneurons mediating transcallosal inhibition from the contralateral hemisphere.

Adult↗

PubMed2003

An electron microscopic examination of the corticospinal projection to the cervical spinal cord in the rat: lack of evidence for cortico-motoneuronal synapses.

We investigated whether direct, cortico-motoneuronal connections are present in the rat, using both light microscopic and electron microscopic techniques. Corticospinal fibres were labelled using the anterograde tracer, biotinylated dextran-amine (BDA), which was injected into forelimb sensorimotor cortex. Motoneurons were retrogradely labelled after injection of cholera toxin subunit B (CTB) into forelimb muscles, contralateral to the injected hemisphere. Terminals of peripheral afferent fibres, which were also labelled by CTB, were easily distinguishable from, and much larger than, BDA-labelled corticospinal terminals. At the light microscope level, corticospinal terminals were found in all laminae contralateral to the injection site, most extensively in laminae VI and VII of cervical segments C5-C8. Although labelling in the ventral horn (lamina IX) was present, it was extremely sparse. A total of 47 corticospinal synapses were studied at the electron microscope level; most of these were in lamina VII and the majority (35/47; 74%) made axo-dendritic contacts with asymmetrical synapses; one made an axo-somatic synapse, and in the remaining 11 cases no postsynaptic structure could be identified. All corticospinal terminals contained spherical boutons. Serial sectioning of eight BDA-labelled corticospinal boutons in lamina IX revealed that most (seven out of eight) did not make synaptic contacts with any neuronal structure, and none made any contact with adjacent dendrites of CTB-labelled motoneurons. Thus these results provide no positive ultrastructural evidence for direct cortico-motoneuronal synaptic connections within lamina IX between corticospinal axon boutons and the proximal dendrites of forelimb motoneurons. The results confirm other lines of evidence suggesting that such connections are not present in the rat.

Afferent Pathways↗

PubMed2003

Task-dependent modulations of cortical oscillatory activity in human subjects during a bimanual precision grip task.

Oscillations are a widespread feature of normal brain activity and have been reported at a variety of different frequencies in different neuronal systems. The demonstration that oscillatory activity is present in motor command signals has prompted renewed interest in the possible functions of synchronous oscillatory activity within the primate sensorimotor system. In the current study, we investigated task-dependent modulations in coupling between sensorimotor cortical oscillators during a bimanual precision grip task. The task required a hold-ramp-hold pattern of grip force to be exerted on a compliant object with the dominant right hand, while maintaining a steady grip with the nondominant hand. We found significant task-related modulation of 15- to 30-Hz coherence between magnetoencephalographic (MEG) activity recorded from the left sensorimotor cortex and electromyographic (EMG) activity in hand muscles on the right side. This coherence was maximal during steady hold, but disappeared during the ramp movements. Interestingly coherence between the right sensorimotor MEG and left-hand EMG showed a similar, although less deeply modulated, task-related pattern, even though this hand was maintaining a simple steady grip. No significant ipsilateral MEG-EMG coherence was observed in the 15- to 30-Hz passband for either hand. These results suggest that the cortical oscillators in the two sensorimotor cortices are independent to some degree but that they may share a common mechanism that attenuates the cortical power in both hemispheres in the 15- to 30-Hz range during movements of one hand. The results are consistent with the hypothesis that oscillatory activity in the motor system is important in resetting the descending motor commands needed for changes in motor state, such as those that occur in the transition from movement to steady grip.

Adult↗

PubMed2003

Problem of dural scarring in recording from awake, behaving monkeys: a solution using 5-fluorouracil.

In studies using single neuron recordings from awake, behaving monkeys, it is necessary to make repeated transdural penetrations using fragile microelectrodes. The tough connective tissue that accumulates after the dura mater is first exposed is often problematic because of electrode breakage and the mechanical stress to the underlying brain tissue caused by excessive dimpling during penetration. We describe the use of an antimitotic compound, 5-fluorouracil (5FU) to control the growth of this connective tissue. 5FU can be safely applied for short periods to the exposed dural tissue on a regular basis provided that it is thoroughly rinsed after application. The advantages of using 5FU are fourfold: first, it depresses fibroblast division and minimizes dural growth and scar tissue formation so that penetrations are easier with less electrode damage or breakage. Second, the frequency of surgical procedures required to remove this tissue are greatly reduced, which benefits both the experiment animal and the experiment. Third, 5FU reduces vascularization of the tissue so that its removal is far easier and without significant blood loss. Finally, 5FU seems to inhibit bacterial infections within the recording chamber. In macaque motor cortex, we performed a quantitative study of electrophysiological data recorded from monkeys with and without 5FU treatment. No significant deleterious side effects produced by 5FU could be detected. Likewise, histological examination of cortical tissue underlying treated dura did not reveal any obvious signs of damage by 5FU. We recommend this approach, with the appropriate safety precautions, to all those neurophysiologists using transdural microelectrode methods in chronically prepared experimental animals. It is also possible that this technique may be useful in other situations where there is dural scarring after surgical intervention or injury.

Animals↗

PubMed2003

Facilitation from ventral premotor cortex of primary motor cortex outputs to macaque hand muscles.

We demonstrate that in the macaque monkey there is robust, short-latency facilitation by ventral premotor cortex (area F5) of motor outputs from primary motor cortex (M1) to contralateral intrinsic hand muscles. Experiments were carried out on two adult macaques under light sedation (ketamine plus medetomidine HCl). Facilitation of hand muscle electromyograms (EMG) was tested using arrays of fine intracortical microwires implanted, respectively, in the wrist/digit motor representations of F5 and M1, which were identified by previous mapping with intracortical microstimulation. Single pulses (70-200 microA) delivered to F5 microwires never evoked any EMG responses, but small responses were occasionally seen with double pulses (interval: 3 ms) at high intensity. However, both single- and double-pulse stimulation of F5 could facilitate the EMG responses evoked from M1 by single shocks. The facilitation was large (up to 4-fold with single and 12-fold with double F5 shocks) and occurred with an early onset, with significant effects at intervals of only 1-2 ms between conditioning F5 and test M1 stimuli. A number of possible pathways could be responsible for these effects, although it is argued that the most likely mechanism would be the facilitation, by cortico-cortical inputs from F5, of corticospinal I wave activity evoked from M1. This facilitatory action could be of considerable importance for the coupling of grasp-related neurons in F5 and M1 during visuomotor tasks.

Animals↗

PubMed2002

Modulation of synchrony between single motor units during precision grip tasks in humans.

During precision grip, coherence between motor cortex and hand muscle EMG oscillatory activity in the 15-30 Hz range covaries with the compliance of the manipulated object. The current study investigated whether short-term synchrony and coherence between discharges of single motor units (SMUs) in the first dorsal interosseous (1DI) muscle were similarly modulated by object compliance during precision grip. Eight subjects used index finger and thumb to grip two levers that were under robotic control. Guided by visual feedback of the lever force levels, subjects held the levers against a steady force of 1.3 N for 8 s; they then linearly increased the force to 1.6 N over a 2 s period and held for a further 8 s before linearly decreasing the force back to the 1.3 N level over another 2 s period. Subjects performed the task at two different levels of compliance, each with identical grip force levels. Both surface EMG and SMU activity were recorded from the 1DI muscle. Short-term synchrony between the discharges of pairs of SMUs was assessed in the time domain by cross-correlation and in the frequency domain by coherence analysis. Coherence was seen in two frequency ranges: 6-12 Hz and 15-30 Hz. The compliance of the gripped object had a significant effect on both short-term synchronisation and coherence in the 15-30 Hz range between SMUs; both were greater for the more compliant condition. There was no change in the 6-12 Hz coherence.

Adult↗

PubMed2002

Rhythm generation in monkey motor cortex explored using pyramidal tract stimulation.

We investigated whether stimulation of the pyramidal tract (PT) could reset the phase of 15-30 Hz beta oscillations observed in the macaque motor cortex. We recorded local field potentials (LFPs) and multiple single-unit activity from two conscious macaque monkeys performing a precision grip task. EMG activity was also recorded from the second animal. Single PT stimuli were delivered during the hold period of the task, when oscillations in the LFP were most prominent. Stimulus-triggered averaging of the LFP showed a phase-locked oscillatory response to PT stimulation. Frequency domain analysis revealed two components within the response: a 15-30 Hz component, which represented resetting of on-going beta rhythms, and a lower frequency 10 Hz response. Only the higher frequency could be observed in the EMG activity, at stronger stimulus intensities than were required for resetting the cortical rhythm. Stimulation of the PT during movement elicited a greatly reduced oscillatory response. Analysis of single-unit discharge confirmed that PT stimulation was capable of resetting periodic activity in motor cortex. The firing patterns of pyramidal tract neurones (PTNs) and unidentified neurones exhibited successive cycles of suppression and facilitation, time locked to the stimulus. We conclude that PTN activity directly influences the generation of the 15-30 Hz rhythm. These PTNs facilitate EMG activity in upper limb muscles, contributing to corticomuscular coherence at this same frequency. Since the earliest oscillatory effect observed following stimulation was a suppression of firing, we speculate that inhibitory feedback may be the key mechanism generating such oscillations in the motor cortex.

Algorithms↗

PubMed2002

Digital nerve anaesthesia decreases EMG-EMG coherence in a human precision grip task.

There is increasing evidence that the primary motor cortex is involved in the generation of electromyographic (EMG) oscillations at frequencies in the range of 15-30 Hz that are observed during performance of a precision grip task. Since the level of the corticomuscular coherence varies according to the nature of the object that is gripped, it seemed possible that somatosensory inputs from the hand might affect this coherence. The aim of this study was to investigate whether interrupting cutaneous inputs from the digits would affect the coherence between hand muscles during precision grip of a compliant object. Subjects performed a precision grip hold-ramp-hold task before, during and after digital nerve anaesthesia of the index finger and thumb. There were marked deficits in the performance of the task, particularly during the initial formation of the grip and first hold period. Local digital nerve anaesthesia reduced but did not abolish 14-31 Hz coherence between EMG activity recorded from different hand and forearm muscles. Coherence was measured during the second hold phase of the task. Digital nerve anaesthesia did not affect the predominant frequencies in the EMG power spectra compiled from the same phase of the task. We conclude that during a precision grip task, cutaneous input enhances oscillatory synchrony between pairs of hand muscles.

Adult↗

PubMed2002

A novel algorithm to remove electrical cross-talk between surface EMG recordings and its application to the measurement of short-term synchronisation in humans.

Pairs of discharges of single motor units recorded in the same or different muscles often show synchronisation above chance levels. If large numbers of units are synchronous within and between muscles then the synchrony will be measurable in population recordings such as surface EMG. Measuring synchrony between surface EMG recordings has a number of practical and scientific advantages compared with single motor units recorded from intramuscular electrodes. However, the measurement of such synchrony in the time domain between surface EMGs is complicated because the recordings are contaminated by electrical cross-talk. In this study we recorded surface EMG simultaneously from five hand and forearm muscles during a precision grip task. Using a novel 'blind signal separation' algorithm, we were able to remove electrical cross-talk. The cross-talk-corrected EMGs could then be used to assess task-dependent modulation in both oscillatory (15-30 Hz) and non-oscillatory synchrony (all other frequencies). In agreement with previous studies, the oscillatory component was maximal during steady holding but abolished during movement. By contrast, the non-oscillatory component of the EMG synchrony appeared remarkably constant throughout all phases of the task. We conclude that surface EMG recordings can be of considerable use in the assessment of population synchrony changes, providing that electrical cross-talk between nearby channels is removed using a statistical signal processing technique. Our results show a striking difference in the task-dependent modulation of oscillatory and non-oscillatory synchrony between muscles during a dynamic precision grip task.

Adult↗

PubMed2002

Comparison of direct and indirect measurements of the central motor conduction time in the monkey.

OBJECTIVE: The goal of the present study was to compare the indirect estimate of the central motor conduction time (CMCT) with direct measurement of the corticospinal conduction time between the motor cortex and cervical enlargement in macaque monkeys. METHODS: Responses to transcranial magnetic stimulation of the motor cortex were recorded from intrinsic hand muscles in adult macaque monkeys. The CMCT was calculated by subtracting the peripheral conduction time, measured with the F-wave method, from the latency of the motor evoked potentials (MEPs). In two monkeys, the actual conduction time between the motor cortex and cervical enlargement was measured directly by different invasive techniques. RESULTS: We found that the indirect calculation of CMCT overestimates the corticospinal conduction time to a significant extent. CONCLUSIONS: One possible source of error is an underestimate of the MEP peripheral conduction time. A collision test confirmed this hypothesis and showed that only a marginal proportion of the motoneurones that respond to a weak corticospinal input also participate in the F-wave. A more accurate estimate of the CMCT could be obtained by using the longest F-wave latency, rather than the shortest, to calculate the peripheral conduction time.

Animals↗

PubMed2002

Differences in the corticospinal projection from primary motor cortex and supplementary motor area to macaque upper limb motoneurons: an anatomical and electrophysiological study.

To further our understanding of the functional roles of different motor cortical areas, we made a quantitative comparison of the density of corticospinal projections from primary motor cortex (M1) and supplementary motor area (SMA) to spinal motor nuclei supplying hand and finger muscles in four macaque monkeys. We also compared the action of corticospinal outputs excited by electrical stimulation of these two areas on upper limb motoneurons recorded in three anaesthetized macaques. The hand representations of SMA and M1 were first identified using structural magnetic resonance imaging scans and intracortical microstimulation. In the anatomical study we then made focal injections of wheatgerm agglutinin- horseradish peroxidase into these representations, which were subsequently confirmed by analysis of retrograde cortical labelling. Densitometric analysis showed that corticospinal projections from M1 were denser and occupied a greater proportion of the hand muscle motor nuclei than did projections from SMA. In caudal Th1 the densest projections from M1 occupied 81% of this motoneuronal area, compared with only 6% from SMA. In the electrophysiological study, bipolar intracortical stimulation of the hand representation of M1 and SMA evoked direct (D) and indirect (I) corticospinal volleys. Volleys elicited by M1 stimulation had larger amplitudes and faster conduction velocities than those evoked from the SMA. Intracellular recordings were made from 84 contralateral upper limb motoneurons. M1 and SMA stimulation evoked markedly different responses in tested motoneurons: EPSPs were larger and more common from M1 (88% of motoneurons) than from SMA (48%). Some motoneurons (16/84) showed evidence of excitatory postsynaptic potentials mediated by monosynaptic action of the D-wave evoked from M1; these early effects were not observed from the SMA. In most motoneurons (74/84) EPSPs had segmental latencies indicating that they were due to monosynaptic action of the I-wave. The results are consistent with cortico-motoneuronal (CM) connections originating from both SMA and M1 converging upon single motoneurons, but those from M1 are far more numerous and exert stronger excitatory effects than from the SMA. Thus although they may function in parallel, the two CM projections probably make different contributions to upper limb motor control.

Animals↗

PubMed2001

Motor control: forcing neurons to change.

New research shows that the properties of cells in motor cortex change during learning of new tasks, shedding new light on the neural basis of motor adaptation.

Adaptation, Physiological↗

PubMed2001

Synchronization in monkey motor cortex during a precision grip task. I. Task-dependent modulation in single-unit synchrony.

Neural synchronization in the cortex, and its potential role in information coding, has attracted much recent attention. In this study, we have recorded long spike trains (mean, 33,000 spikes) simultaneously from multiple single neurons in the primary motor cortex (M1) of two conscious macaque monkeys performing a precision grip task. The task required the monkey to use its index finger and thumb to move two spring-loaded levers into a target, hold them there for 1 s, and release for a food reward. Synchrony was analyzed using a time-resolved cross-correlation method, normalized using an estimate of the instantaneous firing rate of the cell. This was shown to be more reliable than methods using trial-averaged firing rate. A total of 375 neurons was recorded from the M1 hand area; 235 were identified as pyramidal tract neurons. Synchrony was weak [mean k' = 1.05 +/- 0.04 (SD)] but widespread among pairs of M1 neurons (218/1359 pairs with above-chance synchrony), including output neurons. Synchrony usually took the form of a broad central peak [average width, 18.7 +/- 8.7 (SD) ms]. There were marked changes during different phases of the task. As a population, synchrony was greatest during the steady hold period in striking contrast to the averaged cell firing rate, which was maximal when the animal was moving the levers into target. However, the modulation of synchrony during task performance showed considerable variation across individual cell pairs. Two types of synchrony were identified: oscillatory (with periodic side lobes in the cross-correlation) and nonoscillatory. Their relative contributions were quantified by filtering the cross-correlations to exclude either frequencies from 18 to 37 Hz or all higher and lower frequencies. At the peak of population synchrony during the hold period, about half (51.7% in one monkey, 56.2% in the other) of the synchronization was within this oscillatory bandwidth. This study provides strong support for assemblies of neurons being synchronized during specific phases of a complex task with potentially important consequences for both information processing within M1 and for the impact of M1 commands on target motoneurons.

Action Potentials↗