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Biomedical subjects

J C Rothwell

Publications and source records attributed to J C Rothwell.

At least 91 records · Page 5Linked to original sources
PubMed2000

Dissociation of motor preparation from memory and attentional processes using movement-related cortical potentials.

The EEG activity preceding self-paced voluntary movements (movement-related cortical potential, MRCP) is smaller if subjects make the same movement each time (regular task) compared with when different movements are made each time (random task). To test whether extra activity in the random task is due to increased motor preparation needed to switch between different movements, or to memory/attentional processes needed to select movements randomly, we compared regular and random movements with an additional alternating task. This alternating task required subjects to make different movements each time as in the random task, but since the task was very simple, the memory/attentional load was similar to that in the regular task. The MRCP was equally large over motor areas in both random and alternating tasks, suggesting that the extra activity over sensorimotor areas reflected processes involved in motor preparation rather than memory/attention. We speculate that, in the regular task, some part of the instructions for the previous movement remains intact, reducing the amount of preparation needed for the next repetition. Thus the MRCP is smaller than in the alternating and random tasks. Although the MRCPs in alternating and random tasks were similar over the motor areas, the random task had more activity than the alternating task in contralateral frontal areas. This part of the MRCP may therefore be related to memory/attentional processes required to randomize the sequence of movements. We conclude that the MRCP contains dissociable components related to motor preparation and memory/attention.

Adult↗
PubMed2000

Muscarinic receptor blockade has differential effects on the excitability of intracortical circuits in the human motor cortex.

The aim of the present study was to investigate whether muscarinic receptor blockade with scopolamine modifies the excitability of specific cortical networks of the human motor cortex as tested with transcranial magnetic stimulation. The effects of scopolamine on the excitability of human motor cortex were investigated in four healthy subjects using transcranial magnetic stimulation before and after an intravenous dose of scopolamine (0.006 mg/kg). We measured the threshold for motor responses, amplitude of motor responses, the duration of the cortical silent period, intracortical inhibition and facilitation, and short-latency inhibition produced by somatosensory input from the hand. In addition, we evaluated the amplitude of motor responses evoked by electrical anodal stimulation, since these responses originate from direct activation of corticospinal axons in the white matter and are not sensitive to changes in cortical excitability. Scopolamine decreased the threshold to magnetic stimuli and increased the amplitude of motor responses evoked by magnetic stimulation. In contrast, motor responses evoked by electrical stimulation were unaffected by administration of scopolamine. Scopolamine also led to a highly significant reduction in the amount of short-latency inhibition produced by somatosensory input from the hand. In contrast, short-latency intracortical inhibition and facilitation were not modified by scopolamine. The differential effect of scopolamine on motor responses evoked by magnetic and electrical stimulation of the motor cortex and the selective effect on somatosensory inhibition demonstrate that muscarinic blockade modifies the excitability of specific cortical networks in the human motor cortex.

Acetylcholine↗
PubMed2000

What do reflex and voluntary mean? Modern views on an ancient debate.

Are the words reflex and voluntary useful scientific concepts, or are they prescientific terms that should be discarded? Physiologists use these words routinely in their publications, in laboratory experiments and, indeed, like most lay people, in their daily lives. The tacit assumption is that we all know, more or less, what they mean. However, the issue has a rich history of philosophical and scientific debate; and, as this article demonstrates, present-day researchers still cannot reach a consensus on the meaning of the words and on whether it is possible to draw a scientific distinction between them. The five authors present five quite different analyses. In broad terms, they split into two camps: those who equate voluntary behaviours with consciousness and suppressibility and those who view all behaviours as sensorimotor interactions, the complexity of which determines whether they are reflexive or voluntary. According to the first view, most movements of daily life are neither purely reflex nor purely voluntary. They fall into the middle ground of automatic motor programs. According to the second view, as neuroscience advances the class of reflex behaviours will grow and the class of voluntary behaviours will shrink.

Animals↗
PubMed2000

The sternocleidomastoid test: an in vivo assay to investigate botulinum toxin antibody formation in humans.

In a small number of patients treated with botulinum toxin (BT) antibody (Ab) formation occurs. BT Ab can be detected by the mouse protection assay (MPA) or by the mouse diaphragm assay (MDA). Both methods, however, have major drawbacks. We tested a method for detecting BT Ab which measures the BT-induced reduction in the electromyographic amplitude of the mean maximal voluntary activation (M-EMG) of the sternocleidomastoid muscle. The M-EMG reduction was compared in 17 patients with cervical dystonia and secondary BT therapy failure to the M-EMG reduction previously measured in controls. Values more than 2 SD below the mean of controls were considered abnormal. Six patients showed BT Ab on the MPA and MDA; all of these had abnormal M-EMG reductions. Eleven patients showed no BT Ab on MPA and MDA testing; in ten of these the M-EMG reduction was normal, and in one it was pathological, but MDA testing later changed to positive under continued BT therapy. The sternocleidomastoid test is easy to perform and produces quantitative results. Since its sensitivity and specificity are at least as good as those of the MDA and the MPA, it can replace them.

Adult↗
PubMed2000

Phase relationships between cortical and muscle oscillations in cortical myoclonus: electrocorticographic assessment in a single case.

AIM: To compare voluntary- and sensory-induced myoclonic jerks using spectral analysis in a subject with cortical myoclonus. METHODS: The coherence, phase and cumulant density estimates were calculated between right electrocorticographic (ECoG) signals and distal left leg muscles in a patient with subdural electrodes inserted over the right sensorimotor cortex. RESULTS: Significant coherence between sensorimotor cortex and muscle was found up to 60 Hz during voluntary induced myoclonic jerks. Additional higher frequency coherence ( approximately 140 and 190 Hz) was found during sensory-induced myoclonic jerks. The cortical signals phase led muscle signals at frequencies >15 Hz by delays consistent with transmission along corticospinal pathways. Below 15 Hz the cortex phase lagged the muscle signals. Polarity reversal of the cumulant density estimate and the ECoG site demonstrating the highest coherence helped to localize the site of the abnormal oscillatory activity to the leg area of the motor cortex. CONCLUSIONS: Oscillations of different frequencies can co-exist at a given location and can both phase lead and lag contralateral muscle. This has implications for cortex-muscle latency measures calculated by back-averaging techniques.

Aged↗
PubMed2000

Direct demonstration of the effect of lorazepam on the excitability of the human motor cortex.

OBJECTIVES: The present study explored the effects of lorazepam, a benzodiazepine with agonist action at the GABA(A) receptor, on human motor cortex excitability as tested using transcranial magnetic stimulation. METHODS: We recorded directly the descending volley evoked by single and paired transcranial magnetic stimulation from the spinal cord of a conscious subject with a cervical epidural electrode before and after a single oral dose of lorazepam. We evaluated the effects of lorazepam on the descending volleys evoked by a single magnetic stimulation and paired cortical stimulation using the intracortical inhibition paradigm (subthreshold conditioning stimulus) and the short latency intracortical facilitation paradigm (suprathreshold conditioning stimulus). RESULTS: Using a single magnetic stimulus lorazepam decreased the amplitude of the later I waves in the descending volley; this was accompanied by a decrease in the amplitude of the evoked EMG response. Using the intracortical inhibition paradigm lorazepam increased the amount of corticocortical inhibition, particularly at 4 and 5 ms interstimulus intervals. There was no effect on the amount of facilitation observed in the short latency intracortical facilitation paradigm. CONCLUSIONS: The present findings provide direct evidence that lorazepam increases the excitability of inhibitory circuits in the human motor cortex.

Aged↗
PubMed2000

The timing of primary orthostatic tremor bursts has a task-specific plasticity.

Primary orthostatic tremor is characterized by unsteadiness and shakiness of the legs while standing. It is due to a remarkably strong and regular EMG modulation at approximately 16 Hz that is thought to be of CNS origin. Previous studies have shown that the tremor frequency is the same in all involved muscles and that the time relation between bursts of activity in different muscles may be fixed (e.g. always co-contracting or always contracting in an alternating pattern). Here we have used frequency domain analysis of postural muscle EMG signals in five primary orthostatic tremor patients and in two normal controls to explore the nature of such fixed timing patterns. The timing is found not to relate simply to the relative conduction times for passage of rhythmic bursts from a central oscillation to different muscles. Indeed, although the timing pattern (expressed as phase) of the 16-Hz EMG bursts in different postural muscles remains constant while the subject adopts a certain steady posture, it is different for different subjects and also changes when the same subject adopts a different posture. It seems unlikely that such complex task-dependent timing relations of rhythmic postural muscle activity are due to the primary pathology of primary orthostatic tremor. Instead, we suggest that the abnormally strong peripheral manifestation of a 16-Hz CNS oscillation merely unmasks normal central processes so that the timing patterns may provide a clue to the nature of postural motor control.

Aged↗
PubMed2000

The impact of deep brain stimulation on executive function in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the internal segment of the globus pallidus (GPi) improves Parkinson's disease and increases frontal blood flow. We assessed the effects of bilateral DBS on executive function in Parkinson's disease patients, seven with electrodes implanted in the STN and six in the GPi. Patients were assessed off medication with stimulators off, on and off again. The groups showed differential change with stimulation on the Reitan Trail-Making test (TMT B) (STN more improved) and on some measures of random number generation and Wisconsin Card Sorting (STN improved, GPi worse with stimulation). Across the groups, stimulation speeded up responding (Stroop control trial, TMT A) and improved performance on paced serial addition and missing digit tests. Conversely, conditional associative learning became more errorful with stimulation across the two groups. In general, change in performance with stimulation was significant for the STN but not the GPi group. These results support two opposite predictions. In support of current models of Parkinson's disease, 'releasing the brake' on frontal function with DBS improved aspects of executive function. Conversely, disruption of basal ganglia outflow during DBS impaired performance on tests requiring changing behaviour in novel contexts as predicted by Marsden and Obeso in 1994.

Association Learning↗
PubMed2000

Coherence between cerebellar thalamus, cortex and muscle in man: cerebellar thalamus interactions.

Local field potentials (LFPs) were recorded in seven unanaesthetized patients between the four adjacent contacts of a macroelectrode stereotactically implanted for the treatment of tremor. The LFPs were presumed to arise predominantly from the nucleus ventralis intermedius (Vim) of the thalamus, the implantation target. They were recorded simultaneously with the ipsilateral EEG and contralateral EMG during an isometric contraction or at rest. The patients had a history of either isolated tremor (essential tremor, n = 2; benign tremulous Parkinson's disease, n = 1) or tremor with signs of a cerebellar syndrome (multiple sclerosis, n = 3; essential tremor and ataxia, n = 1), although clinical tremor was absent at the time of recording because of a temporary microthalamotomy effect in four patients. In patients with isolated tremor, oscillatory activity picked up by contacts in Vim (cerebellar thalamus) was invariably coherent with that in the sensorimotor cortex or contracting muscle in the 8-27 Hz range. Such coherence was absent in two of the four subjects with tremor associated with a cerebellar syndrome. Coherence between LFPs recorded from more caudally placed contacts and the sensorimotor cortex or contracting muscle was negligible in all patients. These caudally placed contacts demonstrated the highest sensory evoked potential in response to median nerve stimulation. Oscillatory activity in the cerebellar thalamus (Vim) lagged behind that in both cortex and muscle. Coherent activity between the cerebellar thalamus (Vim) and the cortex persisted at rest. It is suggested that rhythmicities in the 8-27 Hz range could provide the basis for a temporal framework that is widely distributed within the motor system.

Aged↗
PubMed2000

Abnormal premovement gating of somatosensory input in writer's cramp.

One characteristic of focal dystonia is the sensory trick, by which sensory input to a certain area of the body can reduce abnormal contractions in muscles nearby. This suggests that adjusting the link between sensory input and movement allows motor commands to be issued more effectively from the brain. To explore this sensorimotor link, we studied the attenuation (gating) of somatosensory evoked potentials (SEPs) before and during hand movements in patients with writer's cramp. For premovement gating, 10 patients and 11 age-matched normal subjects were given a warning sound followed 1s later by an electric stimulus to the right median nerve at the wrist. The latter served both as a reaction signal to start a finger extension task and as the input to evoke SEPs over the scalp. Because reaction times always exceeded 70 ms, short-latency SEPs thus obtained were unaffected by the afferents activated by the movement. The amplitudes of frontal N30 components were significantly decreased over the frontal leads compared with SEPs elicited at rest (P: < 0.002) in the normal group, whereas significant gating was found not for N30 but for frontal P22 (P: = 0. 002) in the patient group. For midmovement gating studies, SEPs to the right median nerve stimulation were recorded in 16 patients and 12 age-matched normal subjects at rest, and during active and passive finger extension-flexion movements. In contrast to the premovement SEPs, the frontal N30 was equally gated during active and passive movements both in the patient (P: < or = 0.002) and the normal group (P: < or = 0.003). These findings indicate that in writer's cramp the sensitivity of sensory input channels from the hand is wrongly set by the central command to move. Perhaps the sensory trick, by supplying additional input not usually present during unobstructed movement, is a manoeuvre to correct this imbalance. Dystonia may result not only from abnormalities in the central motor command but also from disturbed central processing of sensory input.

Adult↗
PubMed2000

I-waves in motor cortex.

I-waves refer to high-frequency (approximately 600 Hz) repetitive discharge of corticospinal fibers produced by single-pulse stimulation of the motor cortex. First detected in animal preparations, this multiple discharge can also be recorded in humans with epidural electrodes over the spinal cord, and with recently developed noninvasive paired-pulse transcranial magnetic stimulation protocols. The exact nature of the generation of I-waves is still unclear, but there is convincing evidence that they originate in the motor cortex, mainly through activation of corticocortical projections onto corticospinal neurons. The ability to measure I-waves in human motor cortex allows one to test the integrity and excitability of the underlying corticocortical circuits in health and disease.

Humans↗
PubMed2000

Electromyographic quantification of the paralysing effect of botulinum toxin in the sternocleidomastoid muscle.

The effect of botulinum toxin (BT) upon the human body has so far been measured by using clinical scales monitoring its overall therapeutic effect upon the disorders treated. Clinical scales, however, usually lack sensitivity, are rarely validated and are integrating a number of uncontrollable parameters. After validation of the methodology in a group of 10 controls, we investigated the BT-induced amplitude reduction of the maximal voluntary electromyographic activity (M-EMG amplitude reduction) of the sternocleidomastoid muscle in a group of 34 patients with cervical dystonia undergoing regular BT therapy with Botox (Allergan, Irvine, Calif., USA; n = 16) or Dysport (Ipsen, Maidenhead, UK; n = 18). With Botox doses of 20 mouse units the M-EMG amplitude reduction was 80% (SD = 3.9%, n = 4), with 40 it was 84% (SD = 10.8%, n = 4), with 60 it was 85% (SD = 2.6%, n = 2) and with 80 it was 91% (SD = 5.8%, n = 6). With Dysport doses of 100 mouse units the M-EMG amplitude reduction was 70% (SD = 7.6%, n = 4), with 200 it was 85% (SD = 10.4%, n = 5), with 300 it was 83% (SD = 9.2%, n = 3), with 400 it was 78% (SD = 6.7%, n = 3) and with 500 it was 91% (SD = 5.8%, n = 5). The methodology presented can measure M-EMG amplitude reductions with a precision of about 10%. Dose-efficacy relationships can be used for dose optimisation, evaluation of BT therapy failure and comparison of different preparations and types of BT.

Botulinum Toxins, Type A↗
PubMed2000

Organization and reorganization of human swallowing motor cortex: implications for recovery after stroke.

Swallowing problems can affect as many as one in three patients in the period immediately after a stroke. In some cases this can lead to serious morbidity, in particular malnutrition and pulmonary aspiration. Despite this, swallowing usually recovers to a safe level in the majority of patients within weeks. This propensity for recovery is likely to relate to how the swallowing motor cortex is organized and then reorganized after cerebral injury. In this review, we examine present knowledge on the cortical control of swallowing in humans, and examine the aspects of its organization that are important for compensating for recovery after damage. In addition, we examine approaches which may be useful in speeding up the process of recovery. Swallowing may turn out to be a useful model for studying central nervous system plasticity.

Animals↗
PubMed2000

Neurophysiologic aspects of deep brain stimulation.

Implanting electrodes for deep brain stimulation (DBS) allows performance of a number of different neurophysiologic studies. Before definitive internalization of the device, recording and stimulation through the electrodes is possible. Stimulation of the globus pallidum produced a mixture of excitation and inhibition of ongoing muscle activity. The excitatory response is probably produced by activation of the large-diameter fibers of the corticospinal tract. Stimulation of the thalamus is mainly associated with EMG inhibition. These findings indicate that the effect of stimulation may vary in different targets and that the mechanism of action of DBS is heterogeneous. A different type of study concerns those undertaken after chronic DBS of the subthalamic nucleus (STN) and globus pallidum internum (GPi) in parkinsonian patients. Cortical mechanisms subserving movement preparation and execution have been assessed. The main findings were that stimulation had a more prominent effect on execution than on preparation and that this was greater in patients treated with STN DBS than GPi DBS.

Electric Stimulation Therapy↗
PubMed1999

Cortical potentials related to decision-making: comparison of two types of go/no-go decision.

The S1-S2 go/no-go reaction time task has been frequently used to assess volitional inhibition. In this study our aim was to compare the ERPs elicited by S1 and S2 by using a modified S1-S2 paradigm which involved a two-stage go/no-go decision. The go and the no-go S1 ERPs did not differ substantially, and both displayed a prominent negativity with peaks at 260 ms (S1N260) and at 330 ms (S1N330) post-S1. The S1N260 was similar to the N2 from no-go S2 trials. Since after all three types of stimuli, movement is not required and is inappropriate, this negativity may represent the correlate of the voluntary decision to suppress movement. Later, the S1 ERPs were dominated by frontal negativity (S1N330), probably reflecting further processes related to response preparation, while the S2 ERPs displayed a large central and parietal positivity (P3), probably reflecting the processes of evaluation of response accuracy.

Adult↗
PubMed1999

Pre-movement gating of short-latency somatosensory evoked potentials.

Somatosensory evoked potentials (SEPs) are reduced in amplitude during movement (gating). The mechanism involves central gating of afferent input and competition from other afferents activated by the movement. We distinguished these two by giving 11 normal subjects a warning sound followed 1 s later by an electric stimulus to the right median nerve at the wrist. The latter served both as a cue to start a finger movement and as stimulation to evoke SEPs. Gating effects were widespread in frontal (N30) and central (N60) areas, but were also seen, albeit to a lesser extent, in the recordings at P3 (P30). Since finger movement began after the stimulus, such gating must have been purely central in origin, presumably reflecting motor preparation.

Adult↗
PubMed1999

Patterned ballistic movements triggered by a startle in healthy humans.

1. The reaction time to a visual stimulus shortens significantly when an unexpected acoustic startle is delivered together with the 'go' signal in healthy human subjects. In this paper we have investigated the physiological mechanisms underlying this effect. If the commands for the startle and the voluntary reaction were superimposed at some level in the CNS, then we would expect to see alterations in the configuration of the voluntary response. Conversely, if the circuit activated by the startling stimulus is somehow involved in the execution of voluntary movements, then reaction time would be sped up but the configuration of the motor programme would be preserved. 2. Fourteen healthy male and female volunteers were instructed to react as fast as possible to a visual 'go' signal by flexing or extending their wrist, or rising onto tiptoe from a standing position. These movements generated consistent and characteristic patterns of EMG activation. In random trials, the 'go' signal was accompanied by a very loud acoustic stimulus. This stimulus was sufficient to produce a startle reflex when given unexpectedly on its own. 3. The startling stimulus almost halved the latency of the voluntary response but did not change the configuration of the EMG pattern in either the arm or the leg. In some subjects the reaction times were shorter than the calculated minimum time for processing of sensory information at the cerebral cortex. Most subjects reported that the very rapid responses were produced by something other than their own will. 4. We conclude that the very short reaction times were not produced by an early startle reflex adding on to a later voluntary response. This would have changed the form of the EMG pattern associated with the voluntary response. Instead, we suggest that such rapid reactions were triggered entirely by activity at subcortical levels, probably involving the startle circuit. 5. The implication is that instructions for voluntary movement can in some circumstances be stored and released from subcortical structures.

Acoustic Stimulation↗