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Biomedical subjects

J C Rothwell

Publications and source records attributed to J C Rothwell.

At least 73 records · Page 4Linked to original sources
PubMed2001

Comparison of descending volleys evoked by monophasic and biphasic magnetic stimulation of the motor cortex in conscious humans.

The descending spinal volleys evoked by monophasic and biphasic magnetic stimulation of the motor cortex were recorded from a bipolar electrode inserted into the cervical epidural space of four conscious human subjects. The results suggest that both phases of the biphasic pulse are capable of activating descending motor output. The pattern of recruitment of descending activity depends on the intensity of the stimulus and the relative threshold of each volley to each direction of current flow.

Adult↗
PubMed2001

Motor and phosphene thresholds: a transcranial magnetic stimulation correlation study.

OBJECTIVE: To investigate the stability of visual phosphene thresholds and to assess whether they correlate with motor thresholds. BACKGROUND: Currently, motor threshold is used as an index of cortical sensitivity so that in transcranial magnetic stimulation (TMS) experiments, intensity can be set at a given percentage of this value. It is not known whether this is a reasonable index of cortical sensitivity in non-motor and hence whether it should be used in experiments where other cortical areas are targeted. Previous studies have indicated that phosphene threshold might be a suitable alternative in TMS studies of the visual system. METHOD: Using single pulse TMS visual phosphene and motor thresholds were measured in 15 subjects. Both thresholds were retested in seven of these subjects a week later. RESULT: Visual phosphene thresholds, though stable within subjects across the two sessions, showed greater variability than motor thresholds. There was no correlation between the two measures. CONCLUSION: TMS motor thresholds cannot be assumed to be a guide to visual cortex excitability and by extension are probably an inappropriate guide to the cortical excitability of other non-motor areas of the brain. Phosphene thresholds are proposed as a potential standard for inter-individual comparison in visual TMS experiments.

Adult↗
PubMed2001

Uncoupling of contingent negative variation and alpha band event-related desynchronization in a go/no-go task.

OBJECTIVES: To examine how the differences in the sequences of brain activation during the go/no-go delayed response choice reaction time (RT) task are reflected into two concurrent methods of measuring brain electrical activity, the alpha band event-related desynchronization (alpha ERD) and the contingent negative variation (CNV). METHODS: alpha ERD and CNV were calculated using appropriate techniques from the same samples of electroencephalographic activity recorded during performance of a cued choice go/no-go delayed response RT task (i.e. S1 (go/no-go)--S2 paradigm) in 8 healthy subjects. RESULTS: All segments of the CNV traces were different in the go and the no-go conditions. The go CNV traces displayed a typical pattern of slow rising negativity reflecting the build-up of attentional resources necessary for adequate performance of the task. On the other hand, the no-go traces remained close to zero reflecting the 'withdrawal' of further preparation after evaluation of S1. During the same period, both go and no-go ERD traces showed a gradual decrease in alpha band power (desynchronization) that was evident until shortly before the presentation of S2. It was only in the 500 ms before S2 presentation that there was any indication that the go and no-go ERD traces were different, but this did not reach statistical significance. CONCLUSIONS: Our data show that the pattern of the go/no-go difference in alpha ERD traces does not correspond to the pattern that can be seen in the CNV traces. This suggests that there is no direct coupling of CNV and alpha ERD, most probably because they measure different aspects of cortical electrical activity. In addition, the extent of the no-go alpha ERD reveals that refraining from performance of a pre-programmed movement is by no means a passive/inactive process.

Adult↗
PubMed2001

Are the after-effects of low-frequency rTMS on motor cortex excitability due to changes in the efficacy of cortical synapses?

OBJECTIVES: To investigate the mechanisms responsible for suppressing the amplitude of electromyogram (EMG) responses to a standard transcranial magnetic stimulus (TMS) after prior conditioning of the motor cortex with repetitive subthreshold TMS (rTMS) at a frequency of 1 Hz. METHODS: EMG responses from the first dorsal interosseous, abductor pollicis brevis and flexor carpi radialis (FCR) muscles were recorded after suprathreshold TMS of the motor cortex. In some experiments, H-reflexes were also obtained in the FCR. The amplitude of these responses was compared before and after applying from 150 to 1500 rTMS pulses to motor cortex at an intensity of 95% resting motor threshold through the same figure-of-8 coil. RESULTS: When tested with subjects relaxed, rTMS conditioning reduced the amplitude of motor evoked potentials (MEPs) to approximately 60% of pre-conditioning values for 2-10 min after the end of the conditioning train, depending on the number of pulses in the train. There was more suppression with 1500 rTMS pulses than with 150 pulses. There was no effect on H-reflexes. There was no effect on MEPs if the test stimuli were given during active contraction of the target muscle. CONCLUSIONS: The findings confirm previous observations that low-frequency, low-intensity rTMS to motor cortex can produce transient depression of MEP excitability. Since there was no effect on spinal H-reflexes, this is consistent with the idea that some of the suppression occurs because of an effect on the motor cortex itself. The lack of any conditioning effect on MEPs evoked in actively contracting muscle is not readily consistent with the idea that rTMS depresses transmission in synaptic connections to pyramidal cells activated by the test TMS pulse. An alternative explanation is that rTMS reduces the excitability of cortical neurones in relaxed subjects, so that responses to a given input are smaller than before conditioning. Voluntary contraction normalises excitability levels so that the effect is no longer seen.

Adult↗
PubMed2001

Transcranial magnetic stimulation of medial-frontal cortex impairs the processing of angry facial expressions.

Growing evidence suggests that the recognition of different emotional states involves at least partly separable neural circuits. Here we assessed the discrimination of both anger and happiness in healthy subjects receiving transcranial magnetic stimulation (TMS) over the medial-frontal cortex or over a control site (mid-line parietal cortex). We found that TMS over the medial-frontal cortex impairs the processing of angry, but not happy, facial expressions of emotion.

Adult↗
PubMed2001

Abnormal interaction between vestibular and voluntary head control in patients with spasmodic torticollis.

The functional status of vestibulo-collic reflexes in the sternocleidomastoid (SCM) muscles was investigated in 24 patients with spasmodic torticollis using small, abrupt 'drops' of the head. None had been treated with botulinum toxin injections during at least 4 months preceding the study. Eight of the patients, four of whom had been studied before surgery, were also studied after selective peripheral denervation of neck muscles. The reflex was of normal latency and duration in the 'passive drop' condition, in which subjects were instructed not to oppose the fall of the head. To study voluntary interaction with the reflex response, subjects were then asked to flex the neck as quickly as possible after onset of the head drop ('active drop'). In this condition, voluntary responses in patients were delayed, smaller and less effective in counteracting the head fall than in normal subjects. The same abnormalities were also found in patients after surgery when the head posture was improved. Somatosensory/auditory voluntary reaction times in SCM were normal, as was the latency of the startle reflex. We conclude that voluntary interaction with the vestibulo-collic reflex is disrupted in patients with spasmodic torticollis, a finding which corroborates the patients' aggravation of their symptoms by head or body perturbations. Lack of effective interaction between two major systems controlling head position may contribute to torticollis.

Adult↗
PubMed2001

Pathophysiology of bradykinesia in Parkinson's disease.

Bradykinesia means slowness of movement and is one of the cardinal manifestations of Parkinson's disease. Weakness, tremor and rigidity may contribute to but do not fully explain bradykinesia. We argue that bradykinesia results from a failure of basal ganglia output to reinforce the cortical mechanisms that prepare and execute the commands to move. The cortical deficit is most apparent in midline motor areas. This leads to particular difficulty with self-paced movements, prolonged reaction times and abnormal pre-movement EEG activity. Movements are often performed with normally timed EMG bursts but the amount of EMG activity is underscaled relative to the desired movement parameters. There are also abnormalities in sensory scaling and sensorimotor integration. The brain appears to be able to compensate to some degree for the basal ganglia deficit. There is overactivity in the lateral premotor areas during task performance and movements can be speeded by giving sensory cues. Attention to movement is also beneficial. However, we propose that the engagement of compensatory processes may also lead to reduced performance in other tasks. For example, patients' problems in performing more than one task at the same time could result from lack of sufficient resources both to compensate for their basal ganglia deficit and to run two tasks simultaneously. Surgical therapies are unlikely to work solely by normalizing basal ganglia output to that seen in healthy individuals. It seems more plausible that surgery removes an interfering signal that allows more efficient compensation by other structures.

Animals↗
PubMed2001

Arm tremor in cervical dystonia differs from essential tremor and can be classified by onset age and spread of symptoms.

The pathophysiology of arm tremor in patients with cervical dystonia (CD) and its relationship to other types of tremor is unclear. In the present study, we have compared the tremor in these patients with that seen in patients with essential tremor (ET) using two neurophysiological techniques: the triphasic EMG pattern accompanying ballistic wrist flexion movements; and reciprocal inhibition between forearm muscles. During ballistic wrist flexion movements, the latency of the second agonist EMG burst was later in ET than CD patients. This suggests that the mechanism of the arm tremor in CD may differ from that in ET. There was no group difference between reciprocal inhibition in patients with ET or CD. However, there was much more variability in the data from patients with CD. Because of this, we subdivided the CD patients into two groups, group A with normal levels of presynaptic inhibition and group B with reduced or absent presynaptic inhibition. A posteriori, it turned out that the patients in these two subgroups had similar clinical symptoms, but different clinical histories. The arm tremor of patients in group A started simultaneously with torticollis (mean onset age of arm tremor 40 years +/- 20.7 SD, interval between onset of arm tremor and torticollis 0 +/- 2.9 years) whereas it began much earlier (mean onset age 14 years +/- 6 SD) and preceded onset of torticollis by a longer interval (21.6 +/- 17.5 years) in patients of group B. Patients in group A also had less co-contraction in their ballistic wrist movements between the first agonist and the antagonist burst than those patients in group B. We conclude that arm tremor in patients with CD may have a mechanism different from that seen in patients with ET. Moreover, the data imply that there are two subgroups of CD patients with arm tremor, one with a late and simultaneous onset of arm tremor and torticollis (group A), and another with an early onset of arm tremor and later development of torticollis (group B). These groups do not correspond to the currently proposed clinical subdivision of 'dystonic tremor' and 'tremor associated with dystonia'.

Adult↗
PubMed2001

The planning and guiding of reading saccades: a repetitive transcranial magnetic stimulation study.

A previous positron emission tomography study that investigated the cortical areas involved in directing eye movements during text reading showed two areas of extra-occipital asymmetry: left > right posterior parietal cortex (PPC), and right > left frontal eye-field (FEF). We used the temporal resolution of repetitive TMS (rTMS) to isolate the contributions of the left and right PPC and FEF to the planning and execution of rightward reading saccades. We present eye-movement data collected during text reading, which involves the initiation and maintenance of a series of saccades (scanpath). rTMS over the left but not right PPC slowed reading speeds for the whole array of words, indicating that this area is involved throughout the scanpath. rTMS over the right but not the left FEF slowed the time to make the first saccade, but only when triggered before the stimuli appeared, demonstrating that the role of this region is in the preparation of the scanpath. Our results are compatible with the hypotheses that the left PPC maintains reading saccades along a line of text while the right FEF is involved in the preparation of the motor plan for the scanpath at the start of each new line of text.

Adult↗
PubMed2001

Levodopa reversible loss of the Piper frequency oscillation component in Parkinson's disease.

OBJECTIVES: Although Parkinson's disease is typically characterised by bradykinesia, rigidity, and rest tremor, the possibility that two additional motor deficits are manifest during small hand muscle activity was explored-namely, weakness and abnormal physiological tremor. METHODS: A paradigm previously used in normal subjects reliably records the strength, tremor and surface EMG of index finger abducting contractions against a compliant (elastic) resistance. In addition to the well known physiological tremor at around 10 Hz, there are other co existing peak tremor frequencies at around 20 and 40 Hz; the last of these frequencies corresponds to the range of EMG Piper rhythm. The same technique was used to study parkinsonian patients while on and off dopaminergic medication. RESULTS: The maximum strength of finger abduction produced by first dorsal interosseous contraction was considerably lower when patients were off medication (mean (SD) 6.27 (1.49) N when off v 12.33 (3.64) N when on). There was also a marked reduction in the power of Piper frequency finger tremor (p<0.0005) and EMG (p<0.0005) oscillations that did not simply result from weaker contraction. CONCLUSION: As the components of physiological tremor at higher frequencies are thought to derive from CNS oscillations important in motor control, their loss in parkinsonism in association with severe off symptoms may represent an important pathophysiological link between dopaminergic depletion and parkinsonian motor deficits.

Electromyography↗
PubMed2001

Physiology and pathophysiology of the swallowing area of human motor cortex.

Swallowing problems can affect as many as one in three patients in the period immediately after stroke. Despite this, in the majority of cases, recovery usually occurs to a safe level after a month or two. In this review, we show how the organization of the cortical projections to swallowing muscles can account for many of the clinical observations on swallowing after stroke and explain why recovery is common in the long term. In addition, we examine approaches that may be useful in speeding up recovery of swallowing. Swallowing may be a useful model in which to study central nervous reorganization after injury.

Deglutition↗
PubMed2001

Polymyography combined with time-locked video recording (video EMG) for presurgical assessment of patients with cervical dystonia.

We assessed 26 patients with cervical dystonia, in whom botulinum toxin (BT) injections had failed, before selective peripheral denervation. We decided to base the decision which muscle should be denervated on both clinical information and EMG data and focussed on the following features: activity at onset or during 'dystonic spasms' (according to the concept of the 'leading' dystonic muscle), paradoxical activity during voluntary head movements causing restriction of head movements opposite the side of head turn or tilt and activity when symptoms deteriorated during walking. To identify these muscles we developed a new recording system that integrates simultaneous video-taping and polymyography (video EMG) by means of a digital counter, driven by the recording software (resolution 0.1 s), that was fixed in view of the video camera. This system time-locked clinical signs with relevant EMG activity thus allowing demonstration of the above features. These were found in 68% of dystonic muscles with each of them being present in approximately 40%. Video EMG allows an integrated approach to identify overactive neck muscles in patients with cervical dystonia taking into account both relevant clinical findings and EMG data.

Adult↗
PubMed2000

Time-varying changes in corticospinal excitability accompanying the triphasic EMG pattern in humans.

Nine healthy subjects performed single rapid wrist movements from neutral to targets at 20 deg of flexion or extension in response to an auditory cue. Surface EMG was recorded from the wrist flexors and extensors together with wrist position. Movements in both directions were characterised by the usual triphasic pattern of EMG activity in agonist (AG1), antagonist (ANTAG) and again in agonist (AG2) muscles. Single pulses of transcranial magnetic stimulation (TMS) were applied over the motor cortex at an intensity of 80 % of resting threshold at random times between 80 and 380 ms after the cue. We measured the peak-to-peak amplitude of the evoked motor potential (MEP) and the integrated EMG (IEMG) activity that preceded the MEP. In a separate set of experiments H reflexes were elicited in the wrist flexors instead of MEPs. MEP amplitudes in the agonist muscle increased by an average of 10 +/- 8 ms (range -1 to 23 ms) prior to the onset of the AG1 burst and were associated with an increase of over sevenfold in the MEP:IEMG ratio, irrespective of movement direction. Agonist H reflex amplitudes were linearly related to, and increased at the same time as, changes in agonist IEMG. The principal ANTAG burst was not preceded by an increase in the antagonist muscle MEP:IEMG ratio. No relationship was found between the amplitude of the antagonist H reflexes and the preceding antagonist IEMG. Five subjects showed an increase in the MEP:IEMG ratio preceding and during the initial part of the AG2 burst. Our method of analysis shows that changes in motor cortical excitability mediating the initiation of movement occur much closer to the onset of EMG activity (less than 23 ms) than the 80-100 ms lead time previously reported. The lack of such changes before the onset of the ANTAG burst suggests that this may be initiated by a different, perhaps subcortical, mechanism.

Adult↗
PubMed2000

Firing patterns of pallidal cells in parkinsonian patients correlate with their pre-pallidotomy clinical scores.

It is unclear how the disordered activity of cells in the basal ganglia contributes to the symptoms of Parkinson's disease (PD). We recorded from single neurons extracellularly in 3 regions of the globus pallidus (GPe, GPie and GPii) in patients undergoing pallidotomy for PD. Movement-related cell firing patterns, analysed using hidden Markov models, were significantly correlated with patients' preoperative clinical scores (off drugs). Responses of cells in GPii correlated best with the scores for specific motor tasks, rather than general ones related to activities of daily living, but the reverse was true for responses from GPe. In both GPii and GPe, a higher score (i.e. greater parkinsonian severity) was associated with greater variability in cell firing rather than an increase in firing rate itself.

Activities of Daily Living↗
PubMed2000

Short latency inhibition of human hand motor cortex by somatosensory input from the hand.

1. EMG responses evoked in hand muscles by transcranial stimulation over the motor cortex were conditioned by a single motor threshold electrical stimulus to the median nerve at the wrist in a total of ten healthy subjects and in five patients who had electrodes implanted chronically into the cervical epidural space. 2. The median nerve stimulus suppressed responses evoked by transcranial magnetic stimulation (TMS) in relaxed or active muscle. The minimum interval between the stimuli at which this occurred was 19 ms. A similar effect was seen if electrical stimulation was applied to the digital nerves of the first two fingers. 3. Median or digital nerve stimulation could suppress the responses evoked in active muscle by transcranial electrical stimulation over the motor cortex, but the effect was much less than with magnetic stimulation. 4. During contraction without TMS, both types of conditioning stimuli evoked a cutaneomuscular reflex that began with a short period of inhibition. This started about 5 ms after the inhibition of responses evoked by TMS. 5. Recordings in the patients showed that median nerve stimulation reduced the size and number of descending corticospinal volleys evoked by magnetic stimulation. 6. We conclude that mixed or cutaneous input from the hand can suppress the excitability of the motor cortex at short latency. This suppression may contribute to the initial inhibition of the cutaneomuscular reflex. Reduced spinal excitability in this period could account for the mild inhibition of responses to electrical brain stimulation.

Adult↗
PubMed2000

Cortical potentials related to the nogo decision.

The go/nogo reaction time task has been frequently used to assess volitional inhibition. Psychophysiological studies of the correlates of the go/nogo decision have almost exclusively been concerned with N2 and P3 potentials of the event-related potentials (ERPs). However, in studies where the EMG onset latency was available, it was obvious that this latency was shorter than or at least equal to the latencies of the studied cerebral potentials. In this study, by concurrent recording of the EEG and EMG activity we aimed to better define the temporal relationship between cortical activity and motor response. Particularly, we wanted to identify the early (i.e. pre EMG-onset) electrophysiological correlates of the nogo decision. We used a modified S1-S2 paradigm that involved a two-stage go/nogo decision. In this task both S1 and S2 were informative and required the subject to make a decision, but the nature of the decision differed. The decision at S1 involved whether to prepare a movement, whereas the decision at S2 involved whether to initiate or inhibit an already prepared response. To better visualise the nogo decision related components of the ERPs, the go ERPs were subtracted from the corresponding nogo ERPs and difference ERPs were formed. Before EMG onset, a small negative component common to both go/nogo difference traces and corresponding roughly with the N1 wave was detected. It is suggested that this early negativity may be a more specific electrophysiological reflection of the nogo decision proper.

Adult↗
PubMed2000

Long-term changes of GABAergic function in the sensorimotor cortex of amputees. A combined magnetic stimulation and 11C-flumazenil PET study.

Primary sensory and motor areas of the cerebral cortex contain organised maps of the body. These maps appear to reorganise after damage to the peripheral parts of the sensory or motor systems, so that the cortical representation of undamaged structures expands at the expense of the damaged parts. Several studies in animals have suggested that decreased activity of the inhibitory GABAergic neurones is responsible for driving these changes. However, whether similar mechanisms sustain the effects in the longer term in humans is unknown. The present study addressed this question by examining reorganisation of sensorimotor areas of cortex in six unilateral upper limb amputees several years after the initial injury. We measured two independent indices of GABAergic function. Volumes of distribution of GABA(A) receptors were determined from 11C-flumazenil binding measured with positron emission tomography (PET). The strength of inhibition in the motor cortex was measured with paired-pulse transcranial magnetic stimulation. In the six amputees taken as a whole and compared with 24 normal subjects, there was a highly significant increase in 11C-flumazenil binding in the upper limb region of primary sensorimotor cortex bilaterally and in medial frontal cortex of the hemisphere contralateral to the amputation. Surprisingly, however, there was no change in the time course or strength of intra-cortical inhibition in the motor cortex of the amputees compared with matched control subjects. The increased 11C-flumazenil binding may reflect up-regulation of GABA(A) receptors to compensate for a decrease in the GABA content or activity of inhibitory neurones. Up-regulation of GABA(A) receptors may also indicate that long-term changes require stabilisation of cortical organisation.

Adult↗