Abnormal acute changes in upper limb muscle cortical representation areas in the patients with writer's cramp during co-activation of distal and proximal muscles.

AIM: We analysed cortical muscle representation areas during single muscle activation and during the co-activation of several upper arm muscles in the patients with writer's cramp to determine the possible occurrence of abnormal dynamic somatotopic changes in M1, in addition to the static map abnormalities already described in this form of dystonia. METHODS: Using transcranial magnetic stimulation, we assessed cortical representations of medial deltoid, extensor carpi radialis and the first dorsal interosseus muscles in eight patients with writer's cramp and in eight healthy control subjects. Cortical maps were obtained during distal muscles' activation either in isolation or in conjunction with voluntary medial deltoid co-activation. RESULTS: This study showed a difference in the organization of cortical representations of these muscles between the patients with dystonia and control subjects. The first dorsal interosseus and the extensor carpi radialis cortical representation areas were larger in the dystonic group. The cortical representations became larger when the medial deltoid was simultaneously co-activated, and this effect was not observed in the control group. In the dystonic group, the three cortical muscle representations largely overlapped and their centres of gravity were closer. CONCLUSION: Patients with dystonia showed not only a different spatial organization of muscle cortical representation areas, but also abnormal acute somatotopic changes during proximal muscle co-activation. Task-specific motor impairment in writer's cramp may result not only from lack of cortical inhibition and the well-known anomalous cortical organization observed in these patients, but also from abnormal patterns of proximo-distal functional muscle coupling.

Writer's cramp: cortical excitability in tasks involving proximo-distal coordination.

AIM: The aim of this work was to analyse how writer's cramp patients coordinate each element of the proximal to distal upper arm muscle chain during voluntary movement. METHODS: Using transcranial magnetic stimulation, we have assessed motor cortex excitability properties in patients by recording motor-evoked potentials and silent periods in both the extensor carpi radialis (ECR) and the first dorsal interosseus muscles (FDI), activated either in isolation, or in conjunction with voluntary medial deltoid (MD) co-activation during performance of precise tasks. Ten dystonic patients and ten healthy controls were tested. RESULTS: In both test groups, the ECR muscle displayed a similar active motor threshold, but the excitability curves reached higher plateau values, when the proximal MD muscle was co-activated. In the dystonic group, the FDI muscle excitability curves reached higher plateau values when the MD was co-activated, whereas co-activation had no effect on the control group. In the control group, silent periods, in both the ECR and the FDI were longer when the MD was co-activated. This effect was not observed in the dystonic group. CONCLUSION: In the dystonic group, facilitation of the FDI was observed during a task involving proximo-distal coordination. No differences in silent periods were observed when the muscle was activated alone. Our results suggest that such abnormal facilitation is not only an impairment of the central inhibitory mechanisms reported for dystonic patients, but, in addition, represents true abnormality in cortical muscle activation strategies.

Postexercise facilitation of motor evoked potentials elicited by ipsilateral voluntary contraction.

Motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) increase in amplitude when obtained immediately after a period of exercise of the target muscle (postexercise facilitation). We studied postexercise facilitation of MEPs to TMS after periods of voluntary activation of either the ipsilateral or contralateral primary motor cortex (simple finger movements) or supplementary motor area (complex finger movements). Postexercise facilitation of the first dorsal interosseous MEPs occurred ipsilaterally even after simple, unilateral finger movements of the dominant hand. The findings are taken to suggest transcallosal transfer of excitability from the dominant to nondominant cerebral hemisphere, perhaps related to mechanisms involved in bimanual motor coordination.

Circadian latency variability of sympathetic skin responses.

Sympathetic skin responses (SSRs) have been increasingly used as tests for autonomic function in the clinical setting. In spite of the known circadian rhythmicity of sympathetic function, however, normative studies have not addressed the possibility of circadian variability of SSR parameters. Ten normal volunteers (7 men, 3 women, aged 19 to 43) had SSR testing performed in the morning, at noon, and in the early evening, and response latencies and amplitudes were compared for the different day periods. Although amplitude values varied in a random fashion, regardless of the time of testing, there was a statistically significant variability in response latencies, which were, on the average, approximately 150 ms shorter in the morning trials, as compared to the early evening ones. This difference was statistically significant (ANOVA, p < 0.01). We propose that circadian variability of SSR latencies should be taken into account in normative studies of SSR parameters.

Role of intracortical mechanisms in the late part of the silent period to transcranial stimulation of the human motor cortex.

Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) of the human motor cortex produce a silent period (SP) following motor evoked potentials (MEPs). The early part of the SP can be explained by decreased alpha motor neuron excitability, whereas the late part is presumably due to suprasegmental mechanisms. In order to determine the level of the suprasegmental contribution of the generation of SPs, we recorded excitatory and inhibitory responses to TMS, TES and percutaneous electrical brainstem stimulation (PBS) in the voluntarily activated first dorsal interosseous muscle of the hand. Stimulus intensities were set so that PBS and TES induced MEPs with areas equal to or larger than those of MEPs obtained with TMS. This procedure revealed that SPs were 49% and 83% shorter with TES and PBS, respectively, than with TMS. As TMS is more effective than TES or PBS in activating cortical interneurons, these findings support the idea that a significant component of the SP arises from intracortical mechanisms.

Modulation of muscle responses evoked by transcranial magnetic stimulation during the acquisition of new fine motor skills.

1. We used transcranial magnetic stimulation (TMS) to study the role of plastic changes of the human motor system in the acquisition of new fine motor skills. We mapped the cortical motor areas targeting the contralateral long finger flexor and extensor muscles in subjects learning a one-handed, five-finger exercise on the piano. In a second experiment, we studied the different effects of mental and physical practice of the same five-finger exercise on the modulation of the cortical motor areas targeting muscles involved in the task. 2. Over the course of 5 days, as subjects learned the one-handed, five-finger exercise through daily 2-h manual practice sessions, the cortical motor areas targeting the long finger flexor and extensor muscles enlarged, and their activation threshold decreased. Such changes were limited to the cortical representation of the hand used in the exercise. No changes of cortical motor outputs occurred in control subjects who underwent daily TMS mapping but did not practice on the piano at all (control group 1). 3. We studied the effect of increased hand use without specific skill learning in subjects who played the piano at will for 2 h each day using only the right hand but who were not taught the five-finger exercise (control group 2) and who did not practice any specific task. In these control subjects, the changes in cortical motor outputs were similar but significantly less prominent than in those occurring in the test subjects, who learned the new skill.(ABSTRACT TRUNCATED AT 250 WORDS)

Central fatigue as revealed by postexercise decrement of motor evoked potentials.

We have previously shown that the amplitudes of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) were transiently decreased after exercise, indicating fatigue of motor pathways in the central nervous system. The responsible mechanism is apparently decreased efficiency in the generation of the descending volleys in the motor cortex. We also noted a progressive decrement in amplitude from the first to the fourth MEP. To further clarify the mechanism of this phenomenon, 5 subjects were studied with TMS delivered at the rates of 0.1, 0.15, 0.3, 1, 3, and 6 Hz. The effect was best demonstrated at 0.3 Hz, and occurred after both isometric and isotonic exercise. Three of the subjects also had 0.3-Hz percutaneous electrical stimulation of the brainstem, and a decrement in MEP amplitude did not occur. Further, the delivery of TMS during muscle contraction after muscle fatigue failed to produce a decrement. The results are similar to those found at the neuromuscular junction in myasthenia gravis and are consistent with a reduced safety factor of cortical synaptic transmission in central nervous system fatigue.

Differentiation of sensorimotor neuronal structures responsible for induction of motor evoked potentials, attenuation in detection of somatosensory stimuli, and induction of sensation of movement by mapping of optimal current directions.

Transcranial magnetic stimulation (TMS) of the sensorimotor cortex can evoke motor evoked potentials (MEPs), attenuation in detection of somatosensory stimuli (ADSS), and sensation of movement (SOM) referred to the same body part. In this study we tried to differentiate the substrates responsible for these effects. In 6 normal volunteers, TMS was applied with a nearly monopolar Dantec stimulator and a butterfly coil. Optimal scalp location and current direction were determined for induction of MEPs in abductor pollicis brevis (APB), first dorsal interosseous (FDI), and adductor digiti minimi (ADM); SOM in digits 2 and 5 in an ischemically paralyzed hand; and ADSS applied to digits 2 and 5. All 3 muscles' MEPs and SOM and ADSS in both digits were optimally activated from a single scalp position. In all subjects, optimal current directions for MEPs pointed anteriorly; those for ADSS and SOM pointed posteriorly. Optimal current directions showed the same progression in all subjects for MEPs (ADM, FDI, and APB from antero-lateral to antero-medial), ADSS (digit 5 postero-medial, 2 postero-lateral), and SOM (digit 1 through 5 postero-lateral to postero-medial). We conclude that neuronal networks targeting corticospinal neurons responsible for MEPs are different from those leading to SOM and ADSS (which could not be differentiated).

Akinesia in Parkinson's disease. I. Shortening of simple reaction time with focal, single-pulse transcranial magnetic stimulation.

We studied the effects of transcranial magnetic stimulation (TMS) of the motor cortex on simple reaction time (RT) in 10 patients with Parkinson's disease compared with 10 age-matched normal controls. The subjects flexed their right elbow rapidly in response to a visual go-signal. In random trials, TMS was applied to the left motor cortex at varying delays after the go-signal. In trials without TMS, RT was longer in the patients. However, in the trials with subthreshold TMS, RT in the patients became as fast as RT in trials without TMS in the controls. This shortening was associated with normalization of the voluntary triphasic EMG pattern and the pre-movement cortical excitability increase.

Akinesia in Parkinson's disease. II. Effects of subthreshold repetitive transcranial motor cortex stimulation.

We studied the effects of repetitive transcranial stimulation of the motor cortex (rTMS) on choice reaction time (cRT), movement time (MT), and error rate (ER) in a serial reaction-time task in six medicated patients with Parkinson's disease (PD) and 10 age-matched normal controls. In normal subjects, subthreshold 5-Hz rTMS did not significantly change cRT, slightly shortened MT, but increased ER. In the patients, rTMS significantly shortened cRT and MT without affecting ER. These effects did not impair procedural learning. Performance on a grooved peg-board test was improved by rTMS in the same PD patients, especially when they were off medications, but worsened in the normal subjects. Repetitive, subthreshold motor cortex stimulation can improve performance in patients with PD and could be useful therapeutically.

Abnormal facilitation of the response to transcranial magnetic stimulation in patients with Parkinson's disease.

We studied the facilitation of the motor evoked potential (MEP) elicited with transcranial magnetic stimulation by increasing the stimulus intensity and the degree of voluntary activation of the target muscle in patients with Parkinson's disease (PD) and in normal volunteers. The threshold intensity for eliciting MEPs with the muscle at rest did not differ in PD patients and normal subjects. At rest, stimuli of similar intensity, related to the individual's threshold, elicited MEPs with amplitudes consistently larger in patients than in normal subjects, although when we compared the averaged MEP amplitude across all stimulus intensities, the differences reached only borderline statistical significance. Voluntary muscle activation elicited a smaller increase in the MEP area in PD patients than in normal subjects. Increasing the degree of voluntary muscle activation at fixed stimulus intensities elicited a smaller increase of MEP amplitude, duration, and area in PD patients than in normal subjects. These results suggest that control of the excitability of the motor system is abnormal in PD patients, with enhancement of excitability at rest and weak energization during voluntary muscle activation.

Non-invasive differentiation of motor cortical representation of hand muscles by mapping of optimal current directions.

Non-invasive mapping of human motor cortex by stimulating different scalp positions with a magnetic coil held at a constant orientation allows differentiation of proximal and distal arm muscles. This study describes a technique for more precise mapping of closely represented muscles using different orientations of a coil that delivers nearly monopolar current pulses. EMG was recorded from abductor pollicis brevis (APB), first dorsal interosseous (FDI), abductor digiti minimi (ADM), and flexor carpi radialis (FCR) of 9 normal volunteers. Stimuli were delivered from a Dantec stimulator through an 8-shaped coil. The center of the coil was kept flat on the scalp on a given position, and the coil rotated at different angles. The amplitudes of the motor evoked potentials were used for calculation of optimal current directions in the brain for activation of each muscle in each position. The optimal current direction for FCR activation pointed antero-medially. ADM, FDI and APB mapped progressively more antero-laterally. The relationship between current directions was constant across subjects and did not change in different scalp positions. This technique improves the spatial resolution of non-invasive cortical mapping and may express the differences in orientations of interneuronal nets in the precentral gyrus.

Modulation of motor cortical outputs to the reading hand of braille readers.

We used focal transcranial magnetic stimulation to map the motor cortical areas targeting the first dorsal interosseous and the abductor digiti minimi muscles bilaterally in 10 proficient braille readers and 10 blind controls who were matched for age (mean, 50.6 yr) and age at time of blindness (mean, 7.5 yr). The proficient braille readers had learned braille at age 8 to 14 years and used it daily for 5 to 10 hours. Controls had not learned braille until age 17 to 21 years and used it daily for < 1 hour. In the controls, motor representations of the right and left first dorsal interosseous and abductor digiti minimi muscles were not significantly different. However, in the proficient braille readers, the representation of the first dorsal interosseous muscle in the reading hand was significantly larger than that in the nonreading hand or in either hand of the controls. Conversely, the representation of the abductor digiti minimi muscle in the reading hand was significantly smaller than that in the nonreading hand or in either hand of the controls. These differences were not due to differences in motor thresholds. Our results suggest that the cortical representation of the reading finger in proficient braille readers is enlarged at the expense of the representation of other fingers.

Rapid modulation of human cortical motor outputs following ischaemic nerve block.

The amplitudes of motor evoked potentials to transcranial magnetic stimulation from muscles immediately proximal to a temporarily anaesthetized (Bier's block) human forearm increase in minutes after the onset of anaesthesia and return to control values after the anaesthesia subsides. In order to determine the level at which the early modulation of human motor outputs takes place, we recorded maximal H reflexes, peripheral M responses, motor evoked potentials to transcranial magnetic stimulation, and motor evoked potentials to transcranial electrical stimulation and spinal electrical stimulation from a muscle immediately proximal to a limb segment made ischaemic by a pneumatic tourniquet. The amplitudes of motor evoked potentials to transcranial magnetic stimulation, but not to transcranial electrical stimulation and spinal electrical stimulation, were larger during ischaemia, implying that the site of change was in the motor cortex. The maximal H/M ratios were unaffected by ischaemia, indicating that alpha-motor neuron excitability to segmental Ia inputs remained unchanged. The map of cortical representation areas for this muscle obtained with transcranial magnetic stimulation was also enlarged. Taken together, our findings suggest that the temporary removal by ischaemic nerve block of myelinated afferent inputs reduces inhibition at the motor cortical level and that this disinhibition is responsible for the increased excitability of the corticospinal system.

Safety of rapid-rate transcranial magnetic stimulation in normal volunteers.

In 9 normal volunteers, we studied the safety of rapid-rate transcranial magnetic stimulation (rTMS) applied to different scalp positions at various frequencies and intensities. Pure tone threshold audiometry showed temporary threshold shifts in 3 subjects. In the subject stimulated at the highest intensity, rTMS induced a focal, secondarily generalized seizure despite the absence of definite risk factors for seizures. Rapid-rate TMS did not result in any important changes in the neurological examination findings, cognitive performance, electroencephalogram, electrocardiogram, and hormone levels (prolactin, adrenocorticotropic hormone, thyroid-stimulating hormone, luteinizing hormone, and follicle-stimulating hormone). In 10 additional subjects, the electromyographic activity in several contralateral muscles showed that trains of rTMS applied to the motor cortex induced a spread of cortical excitability. The spread of excitability depended on the intensity and frequency of the stimuli and probably constituted an early epileptogenic effect of rTMS. Guidelines for preventing the undesirable side effects of rTMS are offered.

Postexercise depression of motor evoked potentials: a measure of central nervous system fatigue.

Fatigue of voluntary muscular effort is a complex and multifaceted phenomenon. Fatigue of peripheral nervous system components, including the contractile apparatus and the neuromuscular junction, has been well studied. Central nervous system components also fatigue, but studies have lagged for want of objective methods. Transcranial magnetic stimulation is a relatively new technique that can be used to assess central nervous system excitability from the motor cortex to the alpha-motoneuron. In six normal volunteers, including four of the investigators, the amplitudes of motor evoked potentials elicited by transcranial magnetic stimulation were transiently decreased after exercise, indicating fatigue of motor pathways in the central nervous system. The decrease in amplitude was associated with a feeling of fatigue. The mechanism of this phenomenon is apparently decreased efficiency in the generation of the motor command in the motor cortex.

Focal transcranial magnetic stimulation and response bias in a forced-choice task.

The effects of transcranial magnetic stimulation were studied on the performance of a warned, forced-choice response time task by normal adults. The task consisted of extension of the index finger in response to the click produced by the discharge of the magnetic coil (go-signal). The subjects were asked to choose the right or left finger only after the go-signal was delivered. Single magnetic stimuli were delivered to the prefrontal or motor area, and in the control situation, away from the head. Magnetic stimulation affected hand preference only when it was delivered to the motor area. With stimulation of this area, subjects more often chose the hand contralateral to the site stimulated with response times that were mainly less than 200 ms. With longer response times (between 200 and 1100 ms), magnetic stimulation had no effect on hand preference regardless of the site stimulated. Stimulation of prefrontal areas yielded results similar to the control situation. These results suggest that response bias in this paradigm is caused by an effect of magnetic stimulation on neural structures within, or closely related to, the motor areas of the brain. Although the response bias was clear and predictable, the subjects were unaware of its existence. It is possible to influence endogenous processes of movement preparation externally without disrupting the conscious perception of volition.

Electrophysiologic studies in leprosy.

The author reviews the literature on electromyography and nerve conduction velocity studies in leprosy. It is concluded that these studies can be helpful in the early diagnosis of neural involvement, in the elucidation of pathophysiological mechanisms, and in the follow-up of patients under medical and/or surgical treatment.