Biomedical subjects

John Rothwell

Publications and source records attributed to John Rothwell.

17 recordsLinked to original sources

PubMed2007

Abnormal plasticity of the sensorimotor cortex to slow repetitive transcranial magnetic stimulation in patients with writer's cramp.

Previous studies demonstrated functional abnormalities in the somatosensory system, including a distorted functional organization of the somatosensory cortex (S1) in patients with writer's cramp. We tested the hypothesis that these functional alterations render S1 of these patients more susceptible to the "inhibitory" effects of subthreshold 1 Hz repetitive transcranial magnetic stimulation (rTMS) given to S1. Seven patients with writer's cramp and eight healthy subjects were studied. Patients also received rTMS to the motor cortex hand area (M1). As an outcome measure, short-latency afferent inhibition (SAI) was tested. SAI was studied in the relaxed first dorsal interosseous muscle using conditioning electrical stimulation of the index finger and TMS pulses over the contralateral M1. Baseline SAI did not differ between groups. S1 but not M1 rTMS reduced SAI in patients. rTMS had no effects on SAI in healthy subjects. Because SAI is mediated predominantly at a cortical level in the sensorimotor cortex, we conclude that there is an abnormal responsiveness of this area to 1 Hz rTMS in writer's cramp, which may represent a trait toward maladaptive plasticity in the sensorimotor system in these patients.

Adult↗

PubMed2007

A randomized, controlled trial with 6-month follow-up of repetitive transcranial magnetic stimulation and electroconvulsive therapy for severe depression.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) has been reported to be as effective as electroconvulsive therapy (ECT) for major depression. The authors conducted a multicenter randomized, controlled trial to test the equivalence of rTMS with ECT. METHOD: Forty-six patients with major depression referred for ECT were randomly assigned to either a 15-day course of rTMS of the left dorsolateral prefrontal cortex (N=24) or a standard course of ECT (N=22). The primary outcome measures were the score on the 17-item Hamilton Depression Rating Scale (HAM-D) and the proportion of patients with remissions (Hamilton score, <or=8) at the end of treatment. Secondary outcomes included mood self-ratings on the Beck Depression Inventory-II and visual analogue mood scales, Brief Psychiatric Rating Scale (BPRS) score, and both self-reported and observer-rated cognitive changes. The patients were followed up after 6 months. RESULTS: HAM-D scores at the end of treatment were significantly lower for ECT, with 13 patients (59.1%) achieving remission in the ECT group and four (16.7%) in the rTMS group. However, at 6 months the HAM-D scores did not differ between groups. Beck scale, visual analogue mood scale, and BPRS scores were lower for ECT at the end of treatment and remained lower after 6 months. Self- and observer-rated cognitive measures were similar in the two groups. CONCLUSIONS: rTMS was not as effective as ECT, and ECT was substantially more effective for the short-term treatment of depression.

Aged↗

PubMed2006

Aging is associated with contrasting changes in local and distant cortical connectivity in the human motor system.

Pathophysiological changes in neurological and neuropsychiatric diseases are increasingly described in terms of abnormal network connectivity. However, the anatomical integrity and efficacy of connections among multiple brain regions change with aging, even in healthy adults. We combined low-frequency transcranial magnetic stimulation and positron emission tomography to study the age-related changes in regional activation and effective connectivity, associated with voluntary action by healthy adults between 22 and 68 years old. Contrasting effects of aging on the motor network were seen using analyses of regional activation, effective connectivity mediating task-related neuronal activation and effective connectivity in response to transcranial magnetic stimulation. Low-frequency rTMS reduced cerebral blood flow during both movement and resting conditions, at the site of stimulation and neighboring frontal cortex. Aging was associated with increased movement-related activation in premotor cortex, bilaterally. Increasing age also increased the susceptibility of the cortex to the inhibitory effects of rTMS, at the site of stimulation and its contralateral homologue. Moreover, older subjects showed enhanced local effective connectivity, centered on the left premotor cortex, but reduced effective connectivity between distant motor-related cortical areas. We discuss these results in relation to the HAROLD model of aging and propose that there are differential effects of aging on local and distributed neuronal subpopulations in the motor network. This differential effect of aging has important implications for the study of neurodegenerative and cerebrovascular diseases that primarily affect older people, as well as our understanding of the normal aging process.

Adult↗

PubMed2006

Reduction of intracortical inhibition in soleus muscle during postural activity.

Short-interval intracortical inhibition (SICI) decreases during voluntary contraction of the target muscle. It is unknown whether this effect also occurs with postural contractions. We have compared the effects of voluntary and postural contractions on SICI in the soleus (SOL) muscle. We applied transcranial magnetic stimuli (TMS) in subjects under three tasks: sitting at rest (Rest), sitting while activating the SOL muscle (Voluntary), or standing quietly (Postural). In control trials, we applied suprathreshold TMS to obtain unconditioned motor-evoked potentials (MEPs). In test trials, the same TMS was preceded by a subthreshold TMS at different interstimulus intervals (ISIs), to obtain a conditioned MEP. SICI and intracortical facilitation (ICF) were expressed as the decrease or increase in MEP size relative to unconditioned MEPs. There was significant effect of task in mean SICI or mean ICF in SOL. Mean SICI in SOL was 52% in Rest and decreased to 21% in Voluntary and 15% in Postural. Mean ICF in SOL was 132% and decreased to 113% in Voluntary and to 108% in Postural. Mean SICI in SOL was not different in Voluntary and Postural tasks. There was no effect of task in mean SICI or mean ICF in TA. Our results indicate that decrease of SICI with muscle contraction occurs to a similar extent with tonic voluntary and postural activation, suggesting that those contractions require a similar type of cortical involvement. However, it cannot be excluded that some part of the SICI reduction with muscle contraction depends on changes in segmental excitability.

Adult↗

PubMed2006

Transcallosal sensorimotor integration: effects of sensory input on cortical projections to the contralateral hand.

OBJECTIVE: Low amplitude vibration of forearm or hand muscles predominantly activates proprioceptive inputs that influence corticospinal projections in a focal manner, increasing output to the stimulated muscle while reducing output to neighbouring muscles. Modulation of contralateral forearm muscles by vibration has also been reported on one occasion. The aim of the current investigation was to investigate the effects of proprioceptive input from a hand muscle on corticospinal excitability, intracortical inhibition (SICI) and interhemispheric inhibition (IHI) targeting the homologous contralateral muscle. METHODS: Transcranial Magnetic Stimulation (TMS) was delivered to the left cortical hand area of 10 healthy subjects and surface electromyography (EMG) recordings taken from the right First Dorsal Interosseus (FDI) and Abductor Digiti Minimi (ADM). The effect of low amplitude vibration of the left FDI on MEP amplitudes, SICI and IHI targeting the right hand was assessed. RESULTS: Vibration of the left FDI caused a significant reduction in MEP amplitudes in the homologous right FDI but not in the right ADM. SICI and IHI targeting both muscles were also significantly increased. CONCLUSIONS: We conclude that proprioceptive input from a hand muscle reduces the corticospinal excitability of the contralateral homologous muscle. The increases in SICI and IHI suggest that at least some of this effect occurs in the cortex ipsilateral to the stimulus and this may be mediated via transcallosal fibres. SIGNIFICANCE: These results suggest that sensory input can modulate excitability in both motor cortices simultaneously, as well as the relationship between them. Interventions which modulate this transcallosal relationship may become useful in disorders where abnormal IHI is a potential therapeutic target.

Adult↗

PubMed2006

Does brain stimulation after stroke have a future?

PURPOSE OF REVIEW: Transcranial methods of cortical stimulation can induce long-term changes in excitability of the cerebral cortex in humans and may be useful as therapeutic interventions in stroke rehabilitation. RECENT FINDINGS: Two approaches have been tested: (1) increasing excitability of the cortex in the stroke hemisphere and (2) suppression of the non-stroke hemisphere to reduce potential interference with function of the stroke hemisphere. The interventions have been transcranial direct current stimulation, transcranial magnetic stimulation and implanted epidural stimulation. All have been reported to give 10-20% functional improvement in small numbers of patients in single-session studies as well as in a small number of longer-term therapeutic trials. Preliminary experiments in aphasic patients using transcranial magnetic stimulation in an interference design show, however, that stimulation of the nonstroke hemisphere can in some patients reduce verbal fluency, questioning the general applicability of the second approach. SUMMARY: Cortical stimulation appears to be a safe and promising intervention for stroke patients. More studies are needed to assess its long-term benefits on substantial numbers of patients. We need to know what type of intervention is best, which patients are likely to benefit, the optimum time to intervene and the duration of any benefits.

Aphasia↗

PubMed2005

Grip force behavior in Gilles de la Tourette syndrome.

We analyzed predictive and reactive grip force behavior in 15 patients with Gilles de la Tourette syndrome (GTS) and 15 sex- and age-matched healthy control subjects. Nine patients were without medication; six patients were on medication. In a first experiment, participants lifted and held instrumented objects of different weight. In a second experiment, participants performed vertical point-to-point and continuous arm movements at different frequencies with a hand-held object. In a third experiment, preparatory and reactive grip force responses to sudden load perturbations were analyzed when a weight was dropped into a hand-held cup either by the subject or unexpectedly by the experimenter. Compared to the healthy subjects, GTS patients had increased grip forces relative to the load force in all tasks. Despite this finding, they adjusted the grip force to changes in load force (due to either a change in the mass lifted or accelerating the mass during continuous movements) in the same way as healthy subjects. The temporal coupling between grip and load force profiles was also similar in patients and healthy controls, and they displayed normal anticipation of impact forces when they dropped a weight into a hand-held cup. We found no significant effect of medication on the performance of GTS patients, regardless of the task performed. These results are consistent with deficient sensory-motor processing in Gilles de la Tourette syndrome.

Acceleration↗

PubMed2004

Short-term high-frequency transcutaneous electrical nerve stimulation decreases human motor cortex excitability.

Several previous studies have shown that periods of changed sensory input can have after effects on the excitability of the corticospinal system. Here we test whether the parameters of peripheral stimulation conventionally used to treat pain with transcutaneous electrical nerve stimulation (TENS: 90 Hz) also have modulatory effects on the motor system. We measured the amplitude of motor evoked potentials (MEPs) elicited by the focal transcranial magnetic stimulation in the right abductor pollicis brevis and first dorsal interosseous muscles before and after 30 min TENS over the right thenar eminence. In addition, we evaluated tactile and 2-point discrimination thresholds at the same site. TENS transiently reduced MEPs and increased sensory thresholds. This suggests that short-term TENS might have an inhibitory effect on both the sensory and motor systems.

Adult↗

PubMed2004

Memory for fingertip forces: passive hand muscle vibration interferes with predictive grip force scaling.

When subjects repetitively lift an object, the grip force they select is influenced by the mechanical object properties of the preceding lift. Similar effects on grip force scaling are observed whether the subsequent lift is performed with the same hand or the hand contralateral to the preceding lift. Here we demonstrate that passive vibration of the hand muscles involved in the generation of grip force in the interval between two blocks of lifting trials interferes with predictive grip force scaling. Following ten trials in which subjects lifted an object with constant mechanical properties with the dominant hand, muscle vibration was given to the first interosseus and adductor pollicis muscles of the dominant hand during a 10-min rest period. Compared with the last lift preceding vibration, peak rates of grip force increase and peak grip forces were scaled too high during the first lift following vibration whether the lift was made with the dominant or non-dominant hand. Subjects scaled grip force accurately to the object properties within three lifts following vibration. If subjects rested for 10 min after the first ten trials and received no vibration, then there was no significant difference in the peak grip force or its rate of increase between the last lift preceding rest and the first lift following it. We suggest that vibration impairs the memory processes responsible for predictive grip force scaling. Our data are consistent with the recent suggestion that these memory processes are neither specific for a certain motor action nor do they reflect internal representations of mechanical object properties.

Adult↗

PubMed2004

Identification of psychogenic, dystonic, and other organic tremors by a coherence entrainment test.

The differentiation of psychogenic from organic tremors, particularly those of a dystonic nature, can be difficult on clinical grounds. Entrainment of tremulous movements of different body parts into a single rhythm has been used clinically as a means of distinguishing these tremor forms, based on the inability of a patient with hysterical tremor to generate voluntary tapping oscillations independent of their ongoing tremor oscillation. The coherence entrainment test is a quantified electrophysiological entrainment test performed on accelerometer or surface EMG tremor signals. This test was carried out on 25 patients referred with suspected psychogenic tremor or dystonic tremor and on 10 normal subjects attempting to tap two independent voluntary oscillations. Using established and new clinical diagnostic criteria, patients were assigned the following final clinical diagnoses: 6 cases of clinically definite dystonic tremor, 5 cases of probable dystonic tremor, 2 cases of classic essential tremor, 5 cases of clinically definite psychogenic tremor, 3 cases of probable psychogenic tremor and 4 uncertain cases. On comparing these clinical diagnoses with those reached by a coherence entrainment test subsequently carried out on each patient, there was 100% concordance in both clinically definite and clinically probable patients. In uncertain cases, when later clinical information came to light, this also corroborated with the coherence entrainment diagnosis. No normal subjects were able to "mimic" organic tremor. The coherence entrainment test appears to be a sensitive and specific means of distinguishing psychogenic tremor from dystonic and other organic tremors.

Adolescent↗

PubMed2004

Effects of low frequency and low intensity repetitive paired pulse stimulation of the primary motor cortex.

OBJECTIVE: Following a previous report [Bestmann et al. Clin Neurophysiol 2004;115:755-64] that pairs of subthreshold pulses of transcranial magnetic stimulation (TMS) can show temporal summation, we explored whether repeated application of pairs of stimulation could produce long-lasting after effects on the excitability of the human motor cortex. METHODS: Twelve healthy subjects received 25 min repetitive paired pulse magnetic stimulation (paired rTMS) given at a frequency of about 0.6 Hz over the left primary motor cortex (500 paired stimuli in total). The interval between the paired stimuli was 3 ms and the intensity of both stimuli was 80% of active motor threshold. The resting and active motor threshold, MEP recruitment curve, short interval intracortical inhibition (SICI) and facilitation, and the duration of the cortical silent period (SP) were tested for the right first interosseous muscle (FDI) before and two times after the end of 25 min paired rTMS. RESULTS: Prolonged subthreshold paired rTMS produced a significant decrease in excitability in the corticospinal projection to FDI: resting motor threshold was significantly increased and MEP recruitment was significantly decreased, SICI was significantly increased at 2 and 4 ms and the SP was significantly increased in duration. CONCLUSIONS: Prolonged low frequency paired rTMS at subthreshold intensity can modulate cortical excitability by producing inhibitory effects that outlast the period of stimulation.

Adolescent↗

PubMed2004

Induction of long-term plasticity in human swallowing motor cortex following repetitive cortical stimulation.

OBJECTIVE: The excitability of corticobulbar projections to swallowing musculature undergoes remarkable long-term increases after short periods of pharyngeal stimulation. The aim of this study was to investigate the excitability of swallowing motor cortex following repetitive transcranial magnetic stimulation (rTMS). METHODS: Twelve healthy subjects were given 100 rTMS pulses over motor cortex at frequencies of 1, 5 and 10 Hz at an intensity of 80% threshold for corticobulbar activation. The excitability of the corticobulbar projection was assessed before and after rTMS and compared both to sham stimulation and to the corticospinal projection. RESULTS: Stimulation at 5 Hz, but not 1 Hz, 10 Hz or sham stimulation increased the excitability of the corticobulbar projection to the pharynx, reaching a peak 60 min after rTMS (Delta increase: 65%, P=0.016). Excitability in the projection from the opposite hemisphere also increased, suggesting the presence of inter-hemispheric interactions, whereas excitability in the projection to thenar muscles was unchanged. CONCLUSIONS: Corticobulbar and corticospinal projections may differ in response to rTMS, implying differences in relative thresholds of inhibitory and excitatory elements in hand versus swallowing cortex. SIGNIFICANCE: This might be a useful approach in the motor rehabilitation of dysphagic stroke patients who have damage to sensory projections to the swallowing cortex.

Adult↗

PubMed2003

Differential changes in human pharyngoesophageal motor excitability induced by swallowing, pharyngeal stimulation, and anesthesia.

We investigated the effects of water swallowing, pharyngeal stimulation, and oropharyngeal anesthesia on corticobulbar and craniobulbar projections to human swallowing musculature. Changes in pathway excitability were measured via electromyography from swallowed intraluminal pharyngeal and esophageal electrodes to motor cerebral and trigeminal nerve magnetic stimulation. After both water swallowing and pharyngeal stimulation, pharyngoesophageal corticobulbar excitability increased (swallowing: pharynx = 59 +/- 12%, P < 0.001; esophagus = 45 +/- 20%, P < 0.05; pharyngeal stimulation: pharynx = 76 +/- 19%, P < 0.001; esophagus = 45 +/- 23%, P = 0.05), being early with swallowing but late with stimulation. By comparison, craniobulbar excitability increased early after swallowing but remained unaffected by pharyngeal stimulation. After anesthesia, both corticobulbar (pharynx =-24 +/- 10%, P < 0.05; esophagus = -28 +/- 7%, P < 0.01) and craniobulbar excitability showed a late decrease. Thus swallowing induces transient early facilitation of corticobulbar and craniobulbar projections, whereas electrical stimulation promotes delayed facilitation mainly in cortex. With removal of input, both corticobulbar and craniobulbar projections show delayed inhibition, implying a reduction in motoneuron and/or cortical activity.

Adult↗

PubMed2002

Transcranial magnetic stimulation: new insights into representational cortical plasticity.

In the last decade, transcranial magnetic stimulation (TMS) has been used increasingly as a tool to explore the mechanisms and consequences of cortical plasticity in the intact human cortex. Because the spatial accuracy of the technique is limited, we refer to this as plasticity at a regional level. Currently, TMS is used to explore regional reorganization in three different ways. First, it can map changes in the pattern of connectivity within and between different cortical areas or their spinal projections. Important examples of this approach can be found in the work on motor cortex representations following a variety of interventions such as immobilization, skill acquisition, or stroke. Second, TMS can be used to investigate the behavioural relevance of these changes. By applying TMS in its "virtual lesion" mode, it is possible to interfere with cortical function and ask whether plastic reorganization within a distinct cortical area improves function. Third, TMS can be used to promote changes in cortical function. This is achieved by using repetitive TMS (rTMS) to induce short-term functional reorganization in the human cortex. The magnitude and the direction of rTMS-induced plasticity depend on extrinsic factors (i.e. the variables of stimulation such as intensity, frequency, and total number of stimuli) and intrinsic factors (i.e. the functional state of the cortex targeted by rTMS). Since conditioning effects of rTMS are not limited to the stimulated cortex but give rise to functional changes in interconnected cortical areas, rTMS is a suitable tool to investigate plasticity within a distributed functional network. Indeed, the lasting effects of rTMS offer new possibilities to study dynamic aspects of the pathophysiology of a variety of diseases and may have therapeutic potential in some neuropsychiatric disorders.

Animals↗

PubMed2002

Driving plasticity in human adult motor cortex is associated with improved motor function after brain injury.

Changes in somatosensory input can remodel human cortical motor organization, yet the input characteristics that promote reorganization and their functional significance have not been explored. Here we show with transcranial magnetic stimulation that sensory-driven reorganization of human motor cortex is highly dependent upon the frequency, intensity, and duration of stimulus applied. Those patterns of input associated with enhanced excitability (5 Hz, 75% maximal tolerated intensity for 10 min) induce stronger cortical activation to fMRI. When applied to acutely dysphagic stroke patients, swallowing corticobulbar excitability is increased mainly in the undamaged hemisphere, being strongly correlated with an improvement in swallowing function. Thus, input to the human adult brain can be programmed to promote beneficial changes in neuroplasticity and function after cerebral injury.

Adult↗

PubMed2002

Bilaterally coherent tremor resembling enhanced physiological tremor: report of three cases.

The contribution of the central nervous system to tremor pathogenesis is unclear. Poor side-to-side coherence in physiological, essential, and parkinsonian tremors suggests distinct bilateral generators. By contrast, significant bilateral coherence demonstrated in orthostatic tremor and in enhanced physiological tremor (EPT) in patients with persistent mirror movements favours single or closely linked bilateral oscillators. We describe three patients (aged 21-37 years) who developed unusual bilateral postural and kinetic tremors at 6-13 Hz resembling EPT. The tremor involved all limbs, and in two cases the face or jaw, in the absence of other significant neurological features. Significant side-to-side coherence was demonstrated in each case using cross-correlation of electromyographic recordings from homologous muscle pairs. We postulate that these unusual tremors originate from a single brainstem source or from bilateral oscillators closely linked at or below this level.

Adult↗

PubMed2002

Neurophysiological investigations in patients with primary writing tremor.

The pathophysiology of primary writing tremor (PWT) is still unknown: it has been classified as a focal form of essential tremor and as a tremulous form of writer's cramp. We studied cortical and spinal excitability in patients with PWT and compared the results with published data of patients with essential tremor, and writer's cramp. We used electrical stimulation of median and radial nerve to study reciprocal inhibition of forearm antagonist muscles and paired transcranial magnetic stimulation at short and long interstimulus intervals (ISIs) to assess intracortical excitability. Both studies were conducted on patients with PWT and on control subjects. The early (presynaptic) and late (disynaptic) phases of reciprocal inhibition were normal as was intracortical excitability at short and long ISIs. Our study suggests that the pathophysiology of PWT is different from that of writer's cramp and partially also from that of essential tremor.

Aged↗