Mechanisms underlying mirror movements in Parkinson's disease: a transcranial magnetic stimulation study.

The neural mechanisms underlying unintended mirror movements (MMs) of one hand during unimanual movements of the other hand in patients with Parkinson's disease (PD) are largely unexplored. Here we used surface electromyographic (EMG) analysis and focal transcranial magnetic stimulation (TMS) to investigate the pathophysiological substrate of MMs in four PD patients. Surface EMG was recorded from both abductor pollicis brevis (APB) and first dorsal interosseous (FDI) muscles. Cross-correlation EMG analysis revealed no common motor drive to the two APBs during intended unimanual tasks. Focal TMS of either primary motor cortex (M1) elicited normal motor-evoked potentials (MEPs) in the contralateral APB, whereas MEPs were not seen in the ipsilateral hand. During either mirror or voluntary APB contraction, focal TMS of the contralateral M1 produced a long-lasting silent period (SP), whereas stimulation of the ipsilateral M1 produced a short-lasting SP. During either mirror or voluntary finger tapping, 5 Hz repetitive TMS (rTMS) of the contralateral M1 disrupted EMG activity in the target FDI, whereas the effects of rTMS of the ipsilateral M1 were by far slighter. During either mirror or voluntary APB contraction, paired-pulse TMS showed a reduction of short-interval intracortical inhibition in the contralateral M1. These findings provide converging evidence that, in PD, MMs do not depend on unmasking of ipsilateral projections but are explained by motor output along the crossed corticospinal projection from the mirror M1.     

Motor control in simple bimanual movements: a transcranial magnetic stimulation and reaction time study.

OBJECTIVE: Simple reaction time (RT) can be influenced by transcranial magnetic stimulation (TMS) to the motor cortex. Since TMS differentially affects RT of ipsilateral and contralateral muscles a combined RT and TMS investigation sheds light on cortical motor control of bimanual movements. METHODS: Ten normal subjects and one subject with congenital mirror movements (MM) were investigated with a RT paradigm in which they had to move one or both hands in response to a visual go-signal. Suprathreshold TMS was applied to the motor cortex ipsilateral or contralateral to the moving hand at various interstimulus intervals (ISIs) after presentation of the go-signal. EMG recordings from the thenar muscles of both hands were used to determine the RT. RESULTS: TMS applied to the ipsilateral motor cortex shortened RT when TMS was delivered simultaneously with the go-signal. With increasing ISI between TMS and go-signal the RT was progressively delayed. This delay was more pronounced if TMS was applied contralateral to the moving hand. When normal subjects performed bimanual movements the TMS-induced changes in RT were essentially the same as if they had used the hand in an unimanual task. In the subject with MM, TMS given at the time of the go-signal facilitated both the voluntary and the MM. With increasing ISI, however, RT for voluntary movements and MM increased in parallel. CONCLUSIONS: Ipsilateral TMS affects the timing of hand movements to the same extent regardless of whether the hand is engaged in an unimanual or a bimanual movement. It can be concluded, therefore, that in normal subjects simple bimanual movements are controlled by each motor cortex independently. The results obtained in the subject with MM are consistent with the hypothesis that mirror movements originate from uncrossed corticospinal fibres. The alternative hypothesis that a deficit in transcallosal inhibition leads to MM in the contralateral motor cortex is not compatible with the presented data, because TMS applied to the motor cortex ipsilateral to a voluntary moved hand affected voluntary movements and MM to the same extent.     

Primary motor cortex and movement prevention: where Stop meets Go

Processes that engage frontal cortex and the basal ganglia are responsible for the prevention of planned movements. Here, we review the role of primary motor cortex (M1) in this function. M1 receives and integrates input from a range of cortical and subcortical sites. It is also the final cortical processing site for voluntary motor commands, before they descend to the spinal cord. Inhibitory networks within M1 may be an important mechanism for the prevention or suppression of movement. Transcranial magnetic stimulation (TMS) has been used to evaluate corticospinal excitability and intracortical inhibition in humans, during the performance of a range of movement selection and prevention tasks. This review explores how M1 intracortical inhibition is selectively reduced to initiate desired voluntary movements, while movement prevention is associated with rapid, non-selective recruitment of inhibition within M1. The relationship between deficient intracortical inhibition and behavioural inhibition is also explored. Examples of neuropathology are reviewed, including focal dystonia, attention deficit hyperactivity disorder and Tourette syndrome. The strengths and limitations of TMS in the study of movement prevention are also discussed. While the precise functional links between M1 neuronal populations and the fronto-basal-ganglia network activated by movement prevention have yet to be elucidated, it is clear that M1 plays a critical role in the final processing stage of response inhibition.     

Dominance of ipsilateral corticospinal pathway in congenital mirror movements

OBJECTIVE: To clarify the mechanism of congenital mirror movements. DESIGN: The triple stimulation technique (TST) and the silent period were used to investigate a patient with congenital mirror movements. The TST was used to calculate the ratio of ipsilateral to contralateral corticospinal tracts from the two hemispheres to the spinal motor neurones. RESULTS: Transcranial magnetic stimulation over unilateral M1 induced larger ipsilateral than contralateral motor evoked potentials on both sides. Only 9% of spinal motor neurones innervating the abductor digitorum minimi were excited by contralateral primary motor cortex (M1) stimulation, while 94% were excited by the ipsilateral M1 stimulation. The silent period was examined during mirror movements and with voluntary contraction of the right first dorsal interosseus mimicking mirror movements. Left M1 stimulation (through the crossed corticospinal tract) did not show any difference in silent period between the two conditions, while right M1 stimulation (through the uncrossed tract) caused a longer silent period during mirror movements than during voluntary contractions. CONCLUSIONS: The results suggest that mirror movements may be caused by a strong connection between ipsilateral M1 and the mirror movements conveyed through a dominant ipsilateral corticospinal pathway.     

Bilateral motor cortex output with intended unimanual contraction in congenital mirror movements

In congenital mirror movements (MM), it is unclear whether the "mirror" motor cortex (M1) produces output during intended unimanual movements. In two patients with MM, the cortical silent period (CSP) was abnormally short after focal transcranial magnetic stimulation (TMS) of either M1, but simultaneous bilateral TMS led to significant CSP lengthening. Thus, it is likely that the shortened CSP after unilateral TMS is caused by output from the nonstimulated M1, suggesting that both M1 produce output with intended unimanual movements in patients with MM.     

Corticospinal excitability is specifically modulated by motor imagery: a magnetic stimulation study

Transcranial magnetic stimulation (TMS) was used to investigate whether the excitability of the corticospinal system is selectively affected by motor imagery. To this purpose, we performed two experiments. In the first one we recorded motor evoked potentials from right hand and arm muscles during mental simulation of flexion/extension movements of both distal and proximal joints. In the second experiment we applied magnetic stimulation to the right and the left motor cortex of subjects while they were imagining opening or closing their right or their left hand. Motor evoked potentials (MEPs) were recorded from a hand muscle contralateral to the stimulated cortex. The results demonstrated that the excitability pattern during motor imagery dynamically mimics that occurring during movement execution. In addition, while magnetic stimulation of the left motor cortex revealed increased corticospinal excitability when subjects imagined ipsilateral as well as contralateral hand movements, the stimulation of the right motor cortex revealed a facilitatory effect induced by imagery of contralateral hand movements only. In conclusion, motor imagery is a high level process, which, however, manifests itself in the activation of those same cortical circuits that are normally involved in movement execution.     

Early non‐specific modulation of corticospinal excitability during action observation

Activity of the primary motor cortex (M1) during action observation is thought to reflect motor resonance. Here, we conducted three studies using transcranial magnetic stimulation (TMS)‐induced motor‐evoked potentials (MEPs) of the first dorsal interosseus muscle (FDI) during action observation to determine: (i) the time course of M1 corticospinal excitability during the observation of a simple finger movement; (ii) the specificity of M1 modulation in terms of type of movement and muscle; and (iii) the relationship between M1 activity and measures of empathy and autistic traits. In a first study, we administered single‐pulse TMS at 30‐ms intervals during the observation of simple finger movements. Results showed enhanced corticospinal excitability occurring between 60 and 90 ms after movement onset. In a second experiment, TMS‐induced MEPs were recorded from the FDI and abductor digiti minimi muscles while pulses were delivered 90 ms after movement onset during observation of simple finger movement and dot movement. Increased corticospinal excitability was restricted to finger movement and was present in both muscles. Finally, in an exploratory experiment, single‐pulse TMS was administered at 30, 90 and 150 ms after movement onset, and participants were asked to complete the Empathy Quotient (EQ) and the Autism Spectrum Quotient (AQ). Correlational analysis revealed a significant link between motor facilitation at 90 ms and the EQ and AQ scores. These results suggest that corticospinal excitability modulation seen at M1 during action observation is the result of a rapid and crude automatic process, which may be related to social functioning.     

Paired Associative Stimulation drives the emergence of motor resonance

BackgroundAssociative plasticity, the neurophysiological bases of Hebbian learning, has been implied in the formation of the association between sensory and motor representations of actions in the Mirror Neuron System; however, such inductor role still needs empirical support.Objective/hypothesisWe have assessed whether Paired Associative Stimulation (PAS), known to activate Hebbian associative plasticity, can induce the formation of atypical (absent in normal conditions), visuo-motor associations, reshaping motor resonance.MethodsHealthy participants underwent a novel PAS protocol (mirror-PAS, m-PAS), during which they were exposed to repeated pairings of transcranial magnetic stimulation (TMS) applied over the right primary motor cortex (M1), time-locked with the view of index-finger movements of the right (ipsilateral) hand. In a first experiment, the inter-stimulus interval (ISI) between visual-action stimuli and TMS pulses was varied. Before and after each m-PAS session, motor resonance was assessed by recording Motor Evoked Potentials induced by single-pulse TMS applied to the right M1, during the observation of both contralateral (left) and ipsilateral (right) index-finger movements. In the second experiment, the specificity of the m-PAS was assessed by presenting a visual stimulus depicting a non-biological movement.ResultsBefore m-PAS, the facilitation of corticospinal excitability occurred only during the view of contralateral (with respect to the TMS side) index-finger movements. The m-PAS induced new ipsilateral motor resonance responses, indexed by atypical facilitation of corticospinal excitability by the view of ipsilateral hand movements. This effect occurred only if the associative stimulation followed the chronometry of motor control (ISI of 25 ms) and if the visual stimulus of the m-PAS depicts a biological movement (human hand action).ConclusionsThe present findings provide the first empirical evidence that Hebbian learning induced by a PAS protocol shapes the visual-motor matching properties of the human Mirror Neuron System.     

Cortical activities associated with voluntary movements and involuntary movements

Recent advance in non-invasive techniques including electrophysiology and functional neuroimaging has enabled investigation of control mechanism of voluntary movements and pathophysiology of involuntary movements in human. Epicortical recording with subdural electrodes in epilepsy patients complemented the findings obtained by the non-invasive techniques. Before self-initiated simple movement, activation occurs first in the pre-supplementary motor area (pre-SMA) and SMA proper bilaterally with some somatotopic organisation, and the lateral premotor area (PMA) and primary motor cortex (M1) mainly contralateral to the movement with precise somatotopic organisation. Functional connectivity among cortical areas has been disclosed by cortico-cortical coherence, cortico-cortical evoked potential, and functional MRI. Cortical activities associated with involuntary movements have been studied by jerk-locked back averaging and cortico-muscular coherence. Application of transcranial magnetic stimulation helped clarifying the state of excitability and inhibition in M1. The sensorimotor cortex (S1-M1) was shown to play an important role in generation of cortical myoclonus, essential tremor, Parkinson tremor and focal dystonia. Cortical myoclonus is actively driven by S1-M1 while essential tremor and Parkinson tremor are mediated by S1-M1. 'Negative motor areas' at PMA and pre-SMA and 'inhibitory motor areas' at peri-rolandic cortex might be involved in the control of voluntary movement and generation of negative involuntary movements, respectively.     

Concurrent bilateral projection and activation of motor cortices in a patient with congenital mirror movements: A TMS study

Objectives

Mirror movements (MMs) are unintended and unnecessary movements accompanying voluntary activity in homologous muscles on the opposite side of the body, particularly in distal arm muscles. Congenital MMs may be sporadic or familial. Several mechanisms have been proposed to explain persistent congenital MMs. Hypothesis 1 assumes the existence of an ipsilateral corticospinal pathway, and Hypothesis 2 the activation of both motor cortices. We report a new case of congenital mirror movements in a healthy woman.

Methods

Electromyographic recordings and focal transcranial magnetic stimulation (TMS) were used for neurophysiological evaluation.

Results

Voluntary contraction of either abductor pollicis brevis (APB) elicited mirror activation of the other APB. Focal TMS of either M1 elicited motor evoked potential (MEP) of normal latency and amplitude in both resting APB. TMS of the left cortex upon maximal contraction of the right APB and mirror contraction of the left APB produced interhemispheric inhibition (IHI) in the former and silent period (SP) in the later.

Conclusions

The electrophysiological evaluation using transcranial magnetic stimulation provides evidence of the concurrent action of both mechanisms in this patient.

Significance

The combination of more than one hypothesis could be more appropriate for understanding the underlying mechanism in some MM cases.     

Effects of motor imagery on finger force responses to transcranial magnetic stimulation

The purpose of this study was to investigate whether characteristics of finger interaction seen in voluntary finger force production tasks could also be observed during motor imagery. Transcranial magnetic stimulation (TMS) was applied over the contralateral M1 hand area. Three conditions were tested in eight young healthy volunteers: At rest, during motor imagery of maximal force production by the index finger (ImIn), and during motor imagery of maximal force production by all four fingers simultaneously (ImAll). We obtained measures of motor threshold (MT), motor-evoked potentials (MEP) from the contralateral flexor digitorium superficialis, and TMS-induced forces from individual fingers. Increased MEP and decreased MT during motor imagery tasks suggested enhanced excitability of structures involved in the generation of TMS-induced responses. TMS-induced forces were larger during motor imagery tasks than at rest. This effect was present, albeit significantly smaller, in the middle, ring, and little fingers during ImIn as compared to ImAll. This finding has been interpreted as a correlate of the phenomenon of unintended finger force production (enslaving). The motor imagery effect on finger forces evoked by TMS was significantly larger during ImIn (4% MVC) than during ImAll (2.8% MVC) tasks, corresponding to the phenomenon of force deficit. These results provide direct evidence of the neural origin of the main phenomena of finger interaction. Furthermore, the similarities between characteristics of finger interaction during motor imagery and during voluntary movement suggest the involvement of similar neural structures (including M1).     

The time course of changes in motor cortex excitability associated with voluntary movement.

The excitability of the motor cortex is modulated before and after voluntary movements. Transcranial magnetic stimulation studies showed increased corticospinal excitability from about 80 and 100 ms before EMG onset for simple reaction time and self-paced movements, respectively. Following voluntary movements, there are two phases of increased corticospinal excitability from 0 to approximately 100 ms and from approximately 100 to 160 ms after EMG offset. The first phase may correspond to the frontal peak of motor potential in movement-related cortical potentials studies and the movement-evoked magnetic field I (MEFI) in magnetoencephalographic (MEG) studies, and likely represents a time when decreasing output from the motor cortex falls below that required for activation of spinal motoneurons, but is still above resting levels. The second phase of increased corticospinal excitability may be due to peripheral proprioceptive inputs or may be centrally programmed representing a subthreshold, second agonist burst. This may correspond to the MEFII in MEG studies. Corticospinal excitability was reduced below baseline levels from about 500 to 1,000 ms after EMG offset, similar to the timing of increase in the power (event-related synchronization, ERS) of motor cortical rhythm. Similarly, motor cortex excitability is reduced at the time of ERS of motor cortical rhythm following median nerve stimulation. These findings support the hypothesis that ERS represents an inactive, idling state of the cortex. The time course of cortical activation is abnormal in movement disorders such as Parkinson's disease and dystonia, reflecting abnormalities in both movement preparation and in cortical excitability following movement.     

Reciprocal change of motor-evoked potentials preceding voluntary movement in humans

Reciprocal change of motor-evoked potentials (MEPs) recorded from the agonist and antagonist muscles of the forearm was studied in 10 normal subjects in whom transcranial magnetic stimulation (TMS) was applied to the hand motor area before voluntary wrist movements. MEP recorded from the agonist muscles, that is, radial extensor muscles for wrist extension and ulnar flexor muscle for wrist flexion, were gradually facilitated with shortening of the interval between the magnetic stimulation and the voluntary muscle contraction. In contrast, MEP recorded from the antagonist muscles, that is, ulnar flexor muscle for wrist extension and radial extensor muscles for wrist flexion, were gradually suppressed as the interval shortened. The reciprocal change of MEP was recognized when TMS was applied within 60 ms prior to the voluntary movements. The present data confirmed that reciprocal change of MEP was recognized before voluntary movements; they further suggest that cortically originated reciprocal control of the corticospinal pathway may exist and that it may be generated just before the voluntary movement. © 1996 John Wiley & Sons, Inc.     

Role of the ipsilateral motor cortex in mirror movements.

The mechanism of mirror movements in two patients was investigated; one with congenital mirror movement, the other with schizencephaly. Transcranial magnetic stimulation on one side elicited motor evoked potentials (MEPs) in their thenar muscles on both sides with almost the same latencies, minimal thresholds, and cortical topographies. During voluntary contraction of the thenar muscle on one side, contralateral transcranial magnetic stimulation induced a silent period not only on the voluntary contraction side but on the mirror movement side and of the same duration. By contrast, ipsilateral transcranial magnetic stimulation elicited MEPs without silent periods in both muscles. With intended unilateral finger movements, an H2(15)O-PET activation study showed that the regional cerebral blood flow increased predominantly in the contralateral sensorimotor cortex, as seen in normal subjects, although mirror movements occurred. It is considered that the ipsilateral motor cortex plays a major part in the generation of mirror movements, which may be induced through the ipsilateral uncrossed corticospinal tract.     

Event-related desynchronization and excitability of the ipsilateral motor cortex during simple self-paced finger movements.

OBJECTIVE: To study the time course of oscillatory EEG activity and corticospinal excitability of the ipsilateral primary motor cortex (iM1) during self-paced phasic extension movements of fingers II-V. METHODS: We designed an experiment in which cortical activation, measured by spectral-power analysis of 28-channel EEG, and cortical excitability, measured by transcranial magnetic stimulation (TMS), were assessed during phasic self-paced extensions of the right fingers II-V in 28 right-handed subjects. TMS was delivered to iM1 0-1500 ms after movement onset. RESULTS: Ipsilateral event-related desynchronization (ERD) during finger movement was paralleled by increased cortical excitability of iM1 from 0-200 ms after movement onset and by increased intracortical facilitation (ICF) without changes in intracortical inhibition (ICI) or peripheral measures (F waves). TMS during periods of post-movement event-related synchronization (ERS) revealed no significant changes in cortical excitability in iM1. CONCLUSIONS: Our findings indicate that motor cortical ERD ipsilateral to the movement is associated with increased corticospinal excitability, while ERS is coupled with its removal. These data are compatible with the concept that iM1 contributes actively to motor control. No evidence for inhibitory modulation of iM1 was detected in association with self-paced phasic finger movements. SIGNIFICANCE: Understanding the physiological role of iM1 in motor control.     

Ipsilateral corticospinal projections do not predict congenital mirror movements: a case report

Congenital mirror movements (CMMs) are involuntary, symmetric movements of one hand during the production of voluntary movements with the other. CMMs have been attributed to a range of physiological mechanisms, including excessive ipsilateral projections from each motor cortex to distal extremities. We examined this hypothesis with an individual showing pronounced CMMs. Mirror movements were characterized for a set of hand muscles during a simple contraction task. Transcranial magnetic stimulation (TMS) was then used to map the relative input to each muscle from both motor cortices. Contrary to our expectations, CMMs were most prominent for muscles with the strongest contralateral representation rather than in muscles that were activated by stimulation of either hemisphere. These findings support a bilateral control hypothesis whereby CMMs result from the recruitment of both motor cortices during intended unimanual movements. Consistent with this hypothesis, bilateral motor cortex activity was evident during intended unimanual movements in an fMRI study. To assess the level at which bilateral recruitment occurs, motor cortex excitability during imagined unimanual movements was assessed with TMS. Facilitory excitation was only observed in the contralateral motor cortex. Thus, the bilateral recruitment of the hemispheres for unilateral actions in individuals with CMMs appears to occur during movement execution rather than motor planning.     

Moving with or without will: functional neural correlates of alien hand syndrome

Alien hand syndrome is a rare neurological disorder in which movements are performed without conscious will. By using functional magnetic resonance imaging in a patient with alien hand syndrome after right parietal lesion, we could identify brain regions activated during involuntary or voluntary actions with the affected left hand. Alien hand movements involved a selective activation of contralateral primary motor cortex (M1), presumably released from conscious control by intentional planning systems. By contrast, voluntary movements activated a distributed network implicating not only the contralateral right M1 and premotor cortex but also the left inferior frontal gyrus, suggesting an important role of the dominant hemisphere in organizing willed actions.     

Corticospinal excitability during motor imagery of a simple tonic finger movement in patients with writer's cramp.

Motor imagery (MI) is the mental rehearsal of a motor act without overt movement. Using transcranial magnetic stimulation (TMS), we tested the effect of MI on corticospinal excitability in patients with writer's cramp. In 10 patients with writer's cramp and 10 healthy controls, we applied focal TMS over each primary motor area and recorded motor evoked potentials (MEPs) from contralateral hand and arm muscles while participants imagined a tonic abduction of the index finger contralateral to the stimulated hemisphere. In healthy controls and patients, the MEP amplitude in the relaxed first dorsal interosseus muscle (FDI) showed a muscle-specific increase during MI; however, the increase was less pronounced in patients than in healthy controls. In addition, in patients but not in controls, the MEP amplitude also increased in hand and forearm muscles not involved in the imagined movement. This abnormal spread of facilitation was observed in the affected and unaffected upper limb. MI of simple hand movements is less efficient and less focussed in patients with writer's cramp than it is in normal subjects.     

Time course of corticospinal excitability in reaction time and self-paced movements

We used transcranial magnetic stimulation (TMS) to study the time course of corticospinal excitability before and after brisk thumb abduction movements, either in a simple reaction time (RT) paradigm or self-paced. Premovement increase in corticospinal excitability began about 20 msec earlier for self-paced compared with simple RT movements. For both simple RT and self-paced movements after electromyographic (EMG) offset, there was a first period of increased excitability from 0 to 100 msec, followed by a second period from 100 to 160 msec. Corticospinal excitability was decreased from about 500 to 1,000 msec after EMG offset for both types of movements. Our results show that motor preparation that begins 1.5 to 2 seconds before self-paced movement is not associated with increased corticospinal excitability. The first phase of increased corticospinal excitability after EMG offset may be due to activity of motor cortex neuron subthreshold for activating spinal motor neurons, and the second phase may reflect a subthreshold second agonist burst. The period of decreased corticospinal excitability after movement corresponds to the onset of event-related synchronization (ERS) of electroencephalographic signals in the 20-Hz band, and supports the hypothesis that ERS may be related to an inactive, idling state of the motor cortex.     

Inhibitory and facilitatory connectivity from ventral premotor to primary motor cortex in healthy humans at rest – A bifocal TMS study

ObjectiveIn macaques, intracortical electrical stimulation of ventral premotor cortex (PMv) can modulate ipsilateral primary motor cortex (M1) excitability at short interstimulus intervals (ISIs).MethodsAdopting the same conditioning-test approach, we used bifocal transcranial magnetic stimulation (TMS) to examine intrahemispheric connectivity between left PMv and M1 in humans. A conditioning stimulus (CS) was applied to PMv at intensities of 80% and 90% of active motor threshold (AMT) and 90% and 110% of resting motor threshold (RMT). A supra-threshold test stimulus (TS) was given 2, 4, 6, 8 and 10 ms after the CS and the amplitude of the motor evoked potential (MEP) was measured to probe corticospinal excitability.ResultsThe CS facilitated corticospinal excitability in ipsilateral M1 when PMv was stimulated with 80% AMT 4 or 6 ms before the TS. At the same ISIs, the CS suppressed corticospinal excitability when the stimulus intensity was increased to 90% RMT. Conditioning effects were site-specific because conditioning the dorsal premotor cortex (PMd) at three different sites produced different effects. Using neuronavigated TMS the PMv site where applied CS produced changes in ipsilateral M1 excitability was located at the border between ventral Brodmann area (BA) 6 and BA 44, the human homologue of monkey’s PMv (area F5).ConclusionWe infer that the corticospinal motor output from M1 to contralateral hand muscles can be facilitated or inhibited by a CS over ipsilateral PMv.SignificanceThe fact that conditioning effects following PMd stimulation differ from those after PMv stimulation supports the concept that inputs from premotor cortices to M1 are functionally segregated.