Study of the silent period following motor evoked potential by magnetic stimulation method

During the voluntary contraction of target muscles, a silent period is observed immediately after the motor evoked potential (MEP) is elicited by transcranial magnetic stimulation. In this study, the silent period was recorded from bilateral abductor digiti minimi (ADM) and abductor hallucis (AH) in 30 normal healthy subjects (120 extremities) and 30 patients with cervical myelopathy (120 extremities). In normal subjects, the silent period was 142.3±41.0 ms (mean±SD) for ADM, and 83.6±42.3 ms for AH. When stimulus intensity was increased from 60% to 95%, the length of the silent period increased, reaching almost maximal level. The length of the silent period correlated with stimulus intensity, but not with the contraction force of voluntary muscles. In patients with cervical myelopathy, the silent period was 69.2±27.8 ms (mean±SD) for ADM and 48.3±17.0 ms for AH, significantly shorter than in the normal subjects. We believe that the length of the silent period can be a useful parameter for indicating the function of the spinal inhibitory system. This work was presented, in part, at the 9th Annual Orthopaedic Research Meeting of the Japanese Orthopaedic Association, Kobe, Japan, 7–8 October 1994, and at the Xth International Congress of EMG and Clinical Neurophysiology, Kyoto, Japan, 15–19 October 1995.     

Magnetic and electrical transcranial brain stimulation: physiological mechanisms and clinical applications

The human brain can be stimulated by electric shocks or by brief intense magnetic fields. The latter cause only a trivial scalp sensation. Stimuli exciting the motor cortex cause contralateral muscle responses, but the threshold for excitation is markedly reduced by slight voluntary contraction of the target muscle. For small hand muscles, the overall latency from scalp to muscle is shorter by 1.8 ms when electrical stimuli are used than when stimuli are magnetic. Central motor conduction time (CMCT) can be estimated by stimulating over the scalp and then over the cervical area. In healthy subjects, the CMCT is 6.1 +/- 0.8 (SD) (n = 29). Physiological studies have shown that the facilitation of responses in hand muscles produced by voluntary contraction is also present when contralateral muscles are used, but not when a leg muscle is contracted. The mechanism of facilitation may involve neural activity at both spinal and cortical levels. Single motor units can be caused to discharge by threshold brain stimuli. These motor units are the same ones activated first during weak voluntary contractions. Clinical studies have shown that the CMCT may be greatly prolonged in patients with multiple sclerosis and that subclinical motor pathway lesions can be detected. Central conduction may also be abnormal in patients with motor neuron disease and cervical myelopathy. Side effects have not been encountered with either type of stimulator.     

The influence of hand posture on corticospinal excitability during motor imagery: a transcranial magnetic stimulation study

In order to study the interaction between proprioceptive information and motor imagery, we herein investigate how compatible and incompatible postural signals influence corticospinal excitability during the mental simulation of hand movements. Subjects were asked to imagine themselves joining the tips of the thumb and the little finger while they maintained one of the two following hand postures: posture A (PA, compatible), little finger, index and thumb extended, the remaining fingers flexed; or posture B (PB, incompatible), index and thumb extended, other fingers flexed. All subjects rated the imagined finger opposition movements as easier to perform when the hand was kept in PA than in PB (P < 0.01) and the correlation between the duration of motor imagery and movement execution was also higher for PA than PB (P < 0.01). For each posture, motor evoked potentials (MEPs) elicited by focal transcranial magnetic stimulation (TMS) of the left motor cortex were recorded from the right opponens pollicis muscle during both motor imagery (MI) and rest (R) conditions. MEP area varied according to the hand posture: PA induced a higher increase in corticospinal excitability, when compared with PB. These results indicate that the actual limb posture affects the process of motor imagery. The source of this postural modulation effect is discussed.     

Corticospinal excitability modulation to hand muscles during movement imagery

Motor evoked potentials (MEPs) to magnetic transcranial stimulation (TCS) were recorded from right abductor digiti minimi (ADM) and first dorsal interosseous (FDI) muscles, sharing the same peripheral innervation but engaged in two different motor demands. In seven healthy and trained subjects, the latencies, amplitudes and variability of MEPs were investigated under the following, randomly intermingled, conditions: full muscular and mental relaxation; mental simulation of selective index finger or little finger abduction; mental non-motor activity (arithmetical calculation); and real motor task (little and index finger abduction). The whole procedure was performed by continuous audiovisual monitoring of electromyographic 'silence' in the tested muscles. The maximal facilitatory effects (= latency shortening and amplitude increase) on MEPs were induced by the real motor task. An amplitude potentiation of MEPs in both tested muscles was present during non-motor mental activity, in comparison to basal values. A further amplitude potentiation, without latency shifts, was confined to the muscle acting as 'prime mover' for the mentally simulated movement, according to the motor program dispatched but not executed by the subject. Similar results were also found in the F-wave, showing that mental simulation affects spinal motoneuronal excitability as well, although -- due to the lack of MEP and F-wave latency shift -- the main effect takes place at cortical level. The study shows that movement imagery can focus specific facilitation on the prime-mover muscle for the mentally simulated movement. This is mainly evident on FDI muscle, which controls fingers (i.e. the index) with highly corticalized motor representation.     

Spinal involvement and muscle cramps in electrically elicited muscle contractions

Electrical stimulation of innervated muscles has been investigated for many decades with alternations of high and low clinical interest in the fields of rehabilitation medicine and sports sciences. Early work demonstrated that afferent fibers have lower thresholds and are usually activated first (therefore eliciting an H-reflex). In the case of nerve trunk stimulation, the order of recruitment is mostly conditioned by the axonal dimension and excitability threshold. In the case of muscle motor point stimulation, the spatial distribution of nerve branches plays a predominant role. Sustained stimulation produces a progressive increase of force that is often maintained in subsequent voluntary activation by stroke patients. This observation suggested a facilitation mechanism at the spinal and/or supraspinal level. Such facilitation has been observed in healthy subjects as well, and may explain the generation of cramps elicited during stimulation and sustained for dozens of seconds after the stimulation has been interrupted. The most recent interpretations of facilitation resulting from peripheral stimulation focused on presynaptic (potentiation of neurotransmitter release from afferent fibers) or postsynaptic (generation of "persistent inward currents" in spinal motor neurons or interneurons) mechanisms. The renewed attention to these phenomena is once more increasing the interest toward electrical stimulation of the neuromuscular system. This is an opportunity for a structured investigation of the field aimed to resolving elements of confusion and controversy that still plague this area of electrophysiology.     

What disconnection tells about motor imagery: evidence from paraplegic patients

Brain activation during motor imagery has been the subject of a large number of studies in healthy subjects, leading to divergent interpretations with respect to the role of descending pathways and kinesthetic feedback on the mental rehearsal of movements. We investigated patients with complete spinal cord injury (SCI) to find out how the complete disruption of motor efferents and sensory afferents influences brain activation during motor imagery of the disconnected feet. Eight SCI patients underwent behavioral assessment and functional magnetic resonance imaging. When compared to a healthy population, stronger activity was detected in primary and all non-primary motor cortical areas and subcortical regions. In paraplegic patients the primary motor cortex was consistently activated, even to the same degree as during movement execution in the controls. Motor imagery in SCI patients activated in parallel both the motor execution and motor imagery networks of healthy subjects. In paraplegics the extent of activation in the primary motor cortex and in mesial non-primary motor areas was significantly correlated with the vividness of movement imagery, as assessed by an interview. The present findings provide new insights on the neuroanatomy of motor imagery and the possible role of kinesthetic feedback in the suppression of cortical motor output required during covert movements.     

Motor evoked potentials of the perineal floor. Preliminary results

Neuromotor pathways from the brain to the pelvic floor have been poorly documented. The recent development of Motor Evoked Potentials may well fill this gap in our basic knowledge. Our technique consists of transcutaneous stimulation of the motor cortex and sacral roots with a magnetic device while recording the evoked response from the bulbocavernosus muscle and anal sphincter. Cortical stimulation is performed first at rest and then during voluntary contraction of the examined muscles ("facilitation" procedure). Sacral root stimulation is performed at rest. Stimulation at 2 different levels allows measurement of the total transit time (brain to muscle transit time) and the peripheral transit time (sacral roots to muscle). By subtracting the latter from the former, the central transit time (brain to sacral roots) is obtained. The technique is painless, and to our knowledge no side effects have been reported. The authors present the preliminary results of this new technique.     

Noninvasive determination of speech dominance by single magnetic stimulation of the bilateral hand motor cortex

Magnetic stimulation of the hand area of the motor cortex in both hemispheres was performed at rest and during reading aloud to observe modulated facilitation of hand muscle motor potentials in 6 right-handed patients, with supratentorial lesions but no motor impairment or aphasia, who had undergone the Wada test to determine speech dominance, showing that 5 were left hemisphere dominant and one was bilateral hemisphere dominant. Motor potentials were facilitated during reading aloud in only the right hand in 3 patients, all left hemisphere dominant, greater in the right hand in one, left hemisphere dominant, and greater in the left hand in one patient, bilateral hemisphere dominant. Based on these results we defined a laterality index which was consistent with the Wada test results. Magnetic stimulation may prove useful for determining cerebral dominance, as our method correlates well with the Wada test, and is safe, convenient, and inexpensive.     

Intracortical hyperexcitability in humans with a GABAA receptor mutation

A missense mutation of the gamma2 subunit of the gamma-aminobutyric acid A (GABA(A)) receptor has been linked to an inherited human generalized epilepsy. As synaptic inhibition in the human brain is largely mediated by the GABA(A) receptor, we tested the hypothesis that the GABRG2(R43Q) mutation alters cortical excitability. Fourteen subjects affected by the GABRG2(R43Q) mutation (5 males, mean age: 44 +/- 15 years) and 24 controls (11 males, mean age: 38 +/- 11 years) were studied with transcranial magnetic stimulation (TMS). To assess the specificity of the effect of the mutation, 4 additional family members unaffected by the GABRG2(R43Q) mutation (2 males, mean age: 41 +/- 16 years) were included. Subjects affected by the GABRG2(R43Q) mutation demonstrated reduced net short-interval intracortical inhibition and increased intracortical facilitation assessed with paired-pulse stimulation. Subjects with the mutation had similar motor thresholds to controls both at rest and with weak voluntary activation. No significant differences were noted between groups in the cortical silent period. Our findings provide in vivo evidence for increased intracortical excitability in subjects affected by the GABRG2(R43Q) mutation. These findings are also likely to represent an important clue to the mechanisms linking this gene defect and the epilepsy phenotype.     

Vision without proprioception modulates cortico-spinal excitability during hand motor imagery

Several studies have shown a cortico-spinal facilitation during motor imagery. This facilitation effect is weaker when the actual hand posture is incompatible with the imagined movement. To determine whether the source of this interference effect arises from online proprioceptive information, we examined transcranial magnetic stimulation (TMS)-induced motor-evoked potentials during motor imagery in the deafferented subject G.L. The patient and 7 control subjects were asked to close their eyes and imagine joining the tips of the thumb and the little finger while maintaining a hand posture compatible or incompatible with the imagined movement. Contrary to control subjects' performance, G.L.'s results show that the facilitation observed during motor imagery was independent of the hand posture. To examine how vision of the hand interacts with the imagery process, G.L. and control subjects performed the same task with the eyes open. Like control subjects, when G.L. looked at her hand, a greater facilitation was observed when her hand posture was compatible with the imagined movement than when it was incompatible. These results suggest that in the absence of proprioception, vision may facilitate or inhibit motor representations and support the idea that limb position in the brain is organized around multisensory representations.     

Zentrales Aktivierungsdefizit des M. deltoideus bei traumatischer Schulterinstabilität

Chronic recurrent anterior shoulder instability (TSI) after primary anterior traumatic shoulder dislocation is a common musculoskeletal problem especially in younger patients. It is unclear if the proprioceptive deficits in patients with TSI lead to central neuromuscular changes. Therefore, this recent study investigated the corticospinal excitability of the deltoid muscle (MD), a key muscle of shoulder function, with transcranial magnetic stimulation (TMS). To achieve this objective the motor-evoked potentials (MEP) in response to TMS of the MD on both sides at rest and low level voluntary activation were obtained from patients with unilateral TSI and compared with age, gender and handedness-matched healthy control subjects. During resting conditions the MEP of the MD showed no differences on both sides between patients and healthy controls. In contrast, the MEP of the MD demonstrated a bilateral hypo-excitability during voluntary activation of MD in patients. This insufficient facilitation of the MD points toward a bilateral central activation deficit. The findings seem to be assigned to adaptive changes in the motor cortex as a consequence of TSI and neuromuscular alteration of the MD should be considered when treating patients with TSI.     

Boosting focally-induced brain plasticity by dopamine

Dopamine (DA) simultaneously produces both excitation and inhibition in the human cortex. In order to shed light on the functional significance of these seemingly opposing effects, we administered the DA precursor levodopa (L-dopa) to healthy subjects in conjunction with 2 neuroplasticity-inducing motor cortex stimulation protocols. Transcranial direct current stimulation (tDCS) induces cortical excitability enhancement by anodal and depression by cathodal brain polarization, which is not restricted to specific subgroups of synapses. In contrast, paired associative stimulation (PAS) induces focal excitability enhancements of somatosensory and motor cortical neuronal synaptic connections. Here, we show that administering L-dopa turns the unspecific excitability enhancement caused by anodal tDCS into inhibition and prolongs the cathodal tDCS-induced excitability diminution. Conversely, it stabilizes the PAS-induced synapse-specific excitability increase. Most importantly, it prolongs all of these aftereffects by a factor of about 20. Hereby, DA focuses synapse-specific excitability-enhancing neuroplasticity in human cortical networks.     

Enhanced cortical activation in the contralesional hemisphere of chronic stroke patients in response to motor skill challenge

The brain processes involved in the restoration of motor skill after hemiparetic stroke are not fully understood. The current study compared cortical activity in chronic stroke patients who successfully recovered hand motor skill and normal control subjects during performance of kinematically matched unskilled and skilled hand movements using functional magnetic resonance imaging. We found that cortical activation during performance of the unskilled movement was increased in the patients relative to controls in the contralesional primary sensorimotor cortex. Performance of the skilled movement elicited increased activation in the patients relative to controls in the contralesional primary sensorimotor cortex, ventral premotor cortex, supplementary motor area/cingulate, and occipitoparietal cortex. Further, the activation change in the contralesional occipitoparietal cortex was greater in the patients relative to controls with the increase in motor skill challenge. Kinematic differences, mirror movements, and residual motor deficits did not account for the enhanced activation in the contralesional cortices in the patients. These results suggest that activation in the contralesional cortical network was enhanced as a function of motor skill challenge in stroke patients with good motor recovery. The findings of the current study suggest that successful recovery of motor skill after hemiparetic stroke involves participation of the contralesional cortical network.     

Assessing recovery in middle cerebral artery stroke using functional MRI

Primary objective: To understand the temporal evolution of brain reorganization during recovery from stroke. Research design: A patient who suffered left middle cerebral artery stroke 9 months earlier was studied on three occasions, ∼1 month apart. Methods and procedures: Brain activation was studied using functional Magnetic Resonance Imaging (fMRI). During each session, the patient performed a finger-to-thumb opposition task, which involved one bimanual and two unimanual conditions. Each condition consisted of overt movement of fingers and imagery of the same task. Results: With recovery, greater recruitment was observed of the affected primary motor cortex (M1) and a decrease in activation of the unaffected M1 and supplementary motor area. In addition, the widespread activation of brain areas seen during the initial session changed to a more focused pattern of activation as the patient recovered. Imagery tasks resulted in similar brain activity as overt execution pointing to imagery as a potential tool for rehabilitation.     

Effects of a competitive stressor on motor cortex excitability: a pilot study

Several intervening variables may influence motor evoked potentials (MEP) from transcranial magnetic stimulation (TMS). Among the most common are motor (e.g. executed or intended muscle contraction) and sensory factors. However, little is known about the effects of a well defined stressor on MEPs and thus on central motor control. We studied 11 healthy right‐handed volunteers (five men and six women), aged 21–32 years (mean 25.2 years, SD=3.5). All subjects underwent a 20 min rest and a 20 min stress period (sequence‐controlled, cross‐over design). The stressor employed a competitive videogame. MEPs from the left abductor digiti minimi muscle were obtained immediately after rest and stress. We found that six (54.5 per cent) subjects presented a significant increase (p<0.05) of MEP amplitudes from rest to stress, three (27.3 per cent; p<0.05) decreased, and two (18.2 per cent) did not change. F‐ and M‐waves did not change significantly. Psychological testing (state and trait anxiety inventory, STAI) revealed that individuals who presented an increase in MEP latency scored lower in state and trait anxiety than others, probably indicating a lower vulnerability to stress. We believe that the observed increase in MEP amplitudes, combined with a decrease in MEP latency, can be regarded as neurophysiological evidence of stress‐induced facilitation related to higher excitability of the corticospinal system and/or presynaptic neurons. Copyright © 2000 John Wiley & Sons, Ltd.     

Effects of subarachnoid lidocaine, meperidine and fentanyl on somatosensory and motor evoked responses in awake humans

Although the effects of local anaesthetics (LA) on motor and sensory transmission in the spinal cord have been described, the effects of opioids are controversial. Our aim was to evaluate the action of clinically relevant doses of subarachnoid (SA) meperidine (MP) and fentanyl (FN), on somatosensory (SSEP) and cortical motor evoked responses (CMER) in awake subjects. Thirty ASA I-II patients scheduled for infra umbilical surgery received SA (N = 10/group): 1 mg/kg lidocaine (LD), 1 mg/kg MP or 25 μg FN. SSEP elicited by stimulation of the posterior tibial nerve at the ankle, and cortical motor evoked response at rest (r-CMER) and during facilitation (f-CMER) were obtained prior and 30 min after treatment. Conduction at the proximal segment of the motor nerve (F-wave) was evaluated by stimulation ot the posterior tibial nerve at the popliteal fossa. Motor/sensory block and side effects were clinically assessed.
LD completely abolished SSEP and CMER. At the same dose, MP abolished SSEP in 40% of the patients, while r-CMER and f-CMER were absent in 70% and 30%, respectively; in addition, the F-wave was absent in 50% of the patients. Fentanyl induced small changes in the latencies of SSEP and F-wave; however, a 28% decrease in the amplitude of the f-CMER (P<0.05) was observed. Pruritus was present in 60% of patients in the FN group (P<0.006).
Our results show that while LD and MP block sensory and motor conduction at the spinal roots, FN seems to decrease the excitability of the spinal interneurons in the corticospinal tract.     

Depression of human corticospinal excitability induced by magnetic theta-burst stimulation: evidence of rapid polarity-reversing metaplasticity

Metaplasticity refers to the activity-dependent modification of the ability of synapses to undergo subsequent potentiation or depression, and is thought to maintain homeostasis of cortical excitability. Continuous magnetic theta-burst stimulation (cTBS; 50 Hz-bursts of 3 subthreshold magnetic stimuli repeated at 5 Hz) is a novel repetitive magnetic stimulation protocol used to model changes of synaptic efficacy in human motor cortex. Here we examined the influence of prior activity on the effects induced by cTBS. Without prior voluntary motor activation, application of cTBS for a duration of 20 s (cTBS300) facilitated subsequently evoked motor potentials (MEP) recorded from APB muscle. In contrast, MEP-size was depressed, when cTBS300 was preceded by voluntary activity of sufficient duration. Remarkably, even without prior voluntary activation, depression of MEP-size was induced when cTBS was extended over 40 s. These findings provide in vivo evidence for extremely rapid metaplasticity reversing potentiation of corticospinal excitability to depression. Polarity-reversing metaplasticity adds considerable complexity to the brain's response toward new experiences. Conditional dependence of cTBS-induced depression of corticospinal excitability on prior neuronal activation suggests that the TBS-model of synaptic plasticity may be closer to synaptic mechanisms than previously thought.     

Circadian modulation of GABA-mediated cortical inhibition

Circadian rhythms exert powerful influence on various aspects of human physiology and behavior. Here, we tested changes of human cerebral cortex excitability over the course of the day with transcranial magnetic stimulation (TMS). At different times of the day, intracortical and corticospinal excitability of the primary motor cortex (M1) was evaluated in 15 healthy subjects by TMS of left M1. While motor thresholds, short-interval intracortical inhibition and facilitation and input/output curves remained unchanged, we found that a specific form of γ-aminobutyric acid (GABA)-mediated intracortical inhibition, revealed by long-interval intracortical inhibition and cortical silent periods, progressively decreased during the course of the day. Additional experiments demonstrated that morning inhibition persisted irrespective of previous sleep or sleep deprivation. Corticotropin-releasing hormone (CRH) infusions in the evening lead to morning cortisol levels but did not restore levels of morning inhibition, whereas suppression of endogenous CRH release by repeated oral dexamethasone intake over 24 h prevented morning inhibition. The findings suggest a specific modulation of GABAergic motor cortex inhibition within the circadian cycle, possibly linked to the CRH system, and may indicate a neurobiological basis for variable neuroplasticity over the course of the day.     

Hemispheric specialization for movement control produces dissociable differences in online corrections after stroke

In this study, we examine whether corrections made during an ongoing movement are differentially affected by left hemisphere damage (LHD) and right hemisphere damage (RHD). Our hypothesis of motor lateralization proposes that control mechanisms specialized to the right hemisphere rely largely on online processes, while the left hemisphere primarily utilizes predictive mechanisms to specify optimal coordination patterns. We therefore predict that RHD, but not LHD, should impair online correction when task goals are unexpectedly changed. Fourteen stroke subjects (7 LHD, 7 RHD) and 14 healthy controls reached to 1 of the 3 targets that unexpectedly "jumped" during movement onset. RHD subjects showed a considerable delay in initiating the corrective response relative to controls and LHD subjects. However, both stroke groups made large final position errors on the target jump trials. Position deficits following LHD were associated with poor intersegmental coordination, while RHD subjects had difficulty terminating their movements appropriately. These findings confirm that RHD, but not LHD, produces a deficit in the timing of online corrections and also indicate that both stroke groups show position deficits that are related to the specialization of their damaged hemisphere. Further research is needed to identify specific neural circuits within each hemisphere critical for these processes.     

Temporary occlusion of associative motor cortical plasticity by prior dynamic motor training

A novel Hebbian stimulation paradigm was employed to examine physiological correlates of motor memory formation in humans. Repetitive pairing of median nerve stimulation with transcranial magnetic stimulation over the contralateral motor cortex (paired associative stimulation, PAS) may decrease human motor cortical excitability at interstimulus intervals of 10 ms (PAS10) or increase excitability at 25 ms (PAS25). The properties of this plasticity have previously been shown to resemble associative timing-dependent long-term depression (LTD) and long-term potentiation (LTP) as established in vitro. Immediately after training a novel dynamic motor task, the capacity of the motor cortex to undergo plasticity in response to PAS25 was abolished. PAS10-induced plasticity remained unchanged. When retested after 6 h, PAS25-induced plasticity recovered to baseline levels. After training, normal PAS25-induced plasticity was observed in the contralateral training-naive motor cortex. Motor training did not reduce the efficacy of PAS25 to enhance cortical excitability when PAS10 was interspersed between the training and application of the PAS25 protocol. This indicated that the mechanism supporting PAS25-induced plasticity had remained intact immediately after training. Behavioral evidence was obtained for continued optimization of force generation at a time when PAS25-induced plasticity was blocked in the training motor cortex. Application of the PAS protocols after motor training did not prevent the consolidation of motor skills evident as performance gains at later retesting. The results are consistent with a concept of temporary suppression of associative cortical plasticity by neuronal mechanisms involved in motor training. Although it remains an open question exactly which element of motor training was responsible for this effect, our findings may link dynamic properties of LTP formation, as established in animal experiments, with human motor memory formation and possibly dynamic motor learning.