Timothy S. Miles

Age and sex differences in human motor cortex input–output characteristics

Stimulus‐response curves for motor evoked potentials (MEPs) induced in a hand muscle by transcranial magnetic stimulation (TMS) were constructed for 42 subjects with the aim of identifying differences related to age and sex. There was no effect of age on the resting threshold to TMS, the maximal amplitude of the MEP that could be evoked (MEPmax) or the maximal slope of the stimulus‐response curve. However, higher stimulus intensities were required to achieve both MEPmax and the maximal slope in the older subjects. The trial‐to‐trial variability of MEPs was greater in the older subjects, particularly at intensities near threshold. There was a significant interaction between age, threshold and trial‐to‐trial variability of MEP amplitude. Overall, MEP variability fell markedly as stimulus intensity increased above threshold but less rapidly in older than in younger subjects. Females tended to have larger MEP variability than males, but age and threshold were much stronger modulators than sex. These differences in input‐output characteristics are likely to be due either to a decreased number of spinal motoneurones being activated synchronously in older subjects, or to the activation of the same number of motoneurones in a less synchronous manner, leading to phase cancellation in the surface electromyogram.

Changes in corticomotor representations induced by prolonged peripheral nerve stimulation in humans

OBJECTIVE Manipulation of afferent input can induce reorganization within the sensorimotor cortex which may have important functional consequences. Here we investigate whether prolonged peripheral nerve stimulation can induce reorganization within the human motor cortex. METHODS Using transcranial magnetic stimulation, we mapped the scalp representation of the corticospinal projection to hand muscles in 8 normal subjects before and after 2h of simultaneous repetitive electrical stimulation of the ulnar and radial nerves at the wrist. Control mapping experiments were conducted in 6 subjects. RESULTS Following nerve stimulation, larger motor-evoked potentials were evoked from more scalp sites. The induced changes were most apparent in first dorsal interosseous, but were also seen in other hand muscles. The increases in area of the representational maps were accompanied by changes in the location of the optimal site for evoking responses in first dorsal interosseous, and changes in the centres of gravity of the maps. CONCLUSIONS Prolonged afferent stimulation induces an increase in excitability of the corticospinal projection. This is accompanied by a significant shift in the centre of gravity of the stimulated muscles which we propose is evidence of a non-uniform expansion in their cortical representation.

Does induction of plastic change in motor cortex improve leg function after stroke

Combined peripheral nerve and brain stimulation (“dual stimulation”) induces changes in the excitability of normal motor cortex. The authors sought to establish whether dual stimulation would also induce motor cortex plasticity and associated functional improvements in nine stroke patients with chronic stable hemiparesis. Following 4 weeks of daily dual stimulation, improvements were seen in some neurophysiological and functional measures. This technique may offer therapeutic opportunities in some stroke patients.

Position sense at the elbow after fatiguing contractions

Fatigue is often associated with increased clumsiness. One possible explanation for this is that the proprioceptive signals from receptors in and around muscles change during muscle fatigue. Thirteen human subjects were tested for their ability to match the elbow angle of one arm with the contralateral arm, before and after a fatiguing contraction of one arm. Contractile fatigue was induced by a series of maximal voluntary contractions of the elbow flexors of the dominant arm. While fatigue of either the target arm or the matching arm usually changed the ability of individual subjects to match arm position, this effect varied markedly from one subject to another and no consistent pattern was discerned. In particular, there was no reciprocal change when the fatigued arm was the matching arm compared with when the nonfatigued arm was the matching arm. The absence of a consistent reciprocal effect indicates that the fatigue-related changes in the ability to match arm position are not solely due to changes in proprioceptive signals and that central fatigue processes are probably involved.

Ia reflexes and EPSPs in human soleus motor neurones

SummaryThe reflex responses of single motor units in the soleus muscle to electrical stimulation of the tibial nerve were recorded in human volunteers. A feature of the experiments was the stimulation paradigm used. In order to control the peristimulus firing rate, a computer triggered the stimulus isolator only when 2 interspike intervals of specified duration occurred in succession. In addition, the timing of the stimulus in relation to the preceding action potential was controlled in a manner similar to a conditioning/testing paradigm. The general pattern of response was an initial, “H-reflex” excitation at monosynaptic latency, followed first by a silent period due to the refractoriness of the motor neurone, then by other phases of reduced activity. When the stimulus intensity was increased, the intensity of the excitation and the duration of the silent period increased in parallel. When the pre-stimulus firing rate of the motor unit was varied, the amplitude of the H-reflex response, normalized to the number of stimulus trials, was similar at 6, 8 and 10 Hz, but was greater at 4 Hz in most units tested. These findings were consistent with a simple model of the events occurring at the cell membrane in this reflex which was proposed by Ashby and Zilm (1982a), although some modification of the model was necessary to account for the different response at 4 Hz. The improved stimulation paradigm enabled a direct estimate to be made of the amplitude and shape of the rising phase of the Ia EPSP in human motor neurones.

Influence of Combined Afferent Stimulation and Task-Specific Training Following Stroke: A Pilot Randomized Controlled Trial

Background. Reorganization of the human motor cortex can be induced by specific patterns of peripheral afferent stimulation. The potential for afferent stimulation to facilitate the functional recovery associated with conventional rehabilitative techniques has not previously been investigated. Objective. The authors sought to determine whether combining appropriate afferent stimulation with task-specific training resulted in greater improvements than training alone in patients with impaired upper limb function in the subacute phase following stroke. Method. Twenty patients with hemiparesis due to stroke were allocated randomly to either a stimulation or control group. All received 9 sessions of task-specific physiotherapy training over 3 weeks. Prior to each training session, associative electrical stimulation of the motor point of 2 hand muscles was given in the stimulation group, whereas the control group received sham stimulation. Changes in dexterity were assessed using a grip-lift task, and standard measures of upper-limb function were made before and following the intervention. Corticospinal excitability was examined using transcranial magnetic stimulation. Results. Both groups showed comparable improvements in functional measures of upper-limb function. Of the 20 patients, only 14 could perform the grip-lift task, which is an objective measure of dexterity. Patients in the stimulation group From the Research Centre for Human Movement Control, School of exhibited significantly greater improvements in this task than the control group. There was no significant change in corticospinal excitability in either group. Conclusion. This pilot study provides preliminary data suggesting that targeted afferent stimulation may facilitate the response to conventional rehabilitation in patients with hemiparesis due to stroke, but these results need to be confirmed in a larger scale study.

Induction of persistent changes in the organisation of the human motor cortex

Motor learning must involve changes in the organisation of the brain, and it seems axiomatic that afferent signals generated during repeated motor practice contribute to this. In this study, motor-point stimulation of the first dorsal interosseous (FDI) muscle was paired with transcranial magnetic stimulation of the human motor cortex on three successive days to determine whether repeated stimulation sessions result in enduring reorganisation of the motor cortex. This repeated “dual” stimulation induced significant changes in the excitability of the motor cortex together with expansion of the area of scalp from which these responses were elicited. The expansion in muscle representation was accompanied by large movements in the centre of gravity (CoG), suggesting a true reorganisation of the underlying cortical representational zone. The changes persisted for at least 2 days following the last stimulation session. It is concluded that repeated dual stimulation is capable of inducing long-lasting reorganisation within the motor cortex. These changes may be similar in nature to those seen in the motor cortex during motor learning. Moreover, these observations suggest that it may be possible to induce the motor cortex of patients who have suffered strokes to reorganise in a way that improves the voluntary control of the weakened muscles.

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

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

Suppression of motor evoked potentials in a hand muscle following prolonged painful stimulation

Earlier investigations have shown that stimulation of peripheral afferent nerves induces prolonged changes in the excitability of the human motor cortex. The present study compared the effect of experimental pain and non‐painful conditioning stimulation on motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in the relaxed first dorsal interosseous (FDI) and flexor carpi ulnaris (FCU) muscles. The MEPs were measured in 10 healthy subjects, and stimulus—response curves were generated before and after each of four stimulation paradigms conducted in random order on separate occasions: (a) control; (b) “dual stimulation” consisting of electrical stimulation of the FDI motor point paired with TMS; (c) painful infusion of hypertonic saline in the FDI muscle; and (d) pain combined with dual stimulation. There were no significant changes in FDI MEPs following the control paradigm, and dual stimulation induced an increase in the FDI MEPs only inconsistently. In contrast, the painful stimulation and the combined pain and dual stimulation paradigms were followed by significant suppression of the FDI MEPs at higher stimulus intensities. No changes were observed in the FCU MEPs following the four paradigms. In two additional subjects, the responses evoked in FDI by direct stimulation of the descending corticospinal tracts were significantly depressed following painful stimulation of the FDI, although the ulnar‐evoked M‐waves remained constant. It is concluded that muscle pain is followed by a period with profound depression of MEPs amplitudes in the resting muscle, but that these changes are at least in part due to a lasting depression of the excitability of the motoneurones in the spinal cord. Hence, painful stimulation differs from non‐painful, repetitive stimulation, which facilitates the corticomotor pathway.

Time course of induction of increased human motor cortex excitability by nerve stimulation

Manipulation of afferent input induces changes in the excitability and organisation of human corticomotor representations. These changes are generally short lived, although can be prolonged by repetition. Here, we charted the time-course of the change of motor cortex excitability induced by electrical stimulation of radial and ulnar nerves. Corticomotor excitability was evaluated by measuring the amplitude of the motor evoked potentials in the first dorsal interosseous muscle by transcranial magnetic stimulation of the optimal cortical area. Measurements were carried out before the start of peripheral nerve stimulation, and then during the peripheral nerve stimulation at 15 min intervals over a period of 2 h. The amplitudes of the motor evoked potentials significantly increased during the 2 h period of peripheral nerve stimulation. Cortical excitability peaked after about 45–60 min stimulation. These clear-cut changes in cortical excitability following peripheral nerve stimulation may reveal some of the mechanisms underlying motor learning and cortical plasticity.