Changes in muscle directional tuning parallel feedforward adaptation to a visuomotor rotation

When people learn to reach in a novel sensorimotor environment, there are changes in the muscle activity required to achieve task goals. Here, we assessed the time course of changes in muscle directional tuning during acquisition of a new mapping between visual information and isometric force production in the absence of feedback-based error corrections. We also measured the influence of visuomotor adaptation on corticospinal excitability, to test whether any changes in muscle directional tuning are associated with adaptations in the final output components of the sensorimotor control system. Nine right-handed subjects performed a ballistic, center-out isometric target acquisition task with the right wrist (16 targets spaced every 22.5° in the joint space). Surface electromyography was recorded from four major wrist muscles, and motor evoked potentials induced by transcranial magnetic stimulation were measured at baseline, after task execution in the absence of the rotation (A1), after adaptation to the rotation (B), and after a final block of trials without rotation (A2). Changes in the directional tuning of muscles closely matched the rotation of the directional error in force, indicating that the functional contribution of muscles remained consistent over the adaptation period. In contrast to previous motor learning studies, we found only minor changes in the amount of muscular activity and no increase in corticospinal excitability. These results suggest that increased muscle co-activation occurs only when the dynamics of the limb are perturbed and/or that online error corrections or altered force requirements are necessary to elicit a component of the adaptation in the final steps of the transformation between motor goal and muscle activation.     

Probing the corticospinal link between the motor cortex and motoneurones: some neglected aspects of human motor cortical function

This review considers the operation of the corticospinal system in primates. There is a relatively widespread cortical area containing corticospinal outputs to a single muscle and thus a motoneurone pool receives corticospinal input from a wide region of the cortex. In addition, corticospinal cells themselves have divergent intraspinal branches which innervate more than one motoneuronal pool but the synergistic couplings involving the many hand muscles are likely to be more diverse than can be accommodated simply by fixed patterns of corticospinal divergence. Many studies using transcranial magnetic stimulation of the human motor cortex have highlighted the capacity of the cortex to modify its apparent excitability in response to altered afferent inputs, training and various pathologies. Studies using cortical stimulation at ‘very low’ intensities which elicit only short-latency suppression of the discharge of motor units have revealed that the rapidly conducting corticospinal axons (stimulated at higher intensities) drive motoneurones in normal voluntary contractions. There are also major non-linearities generated at a spinal level in the relation between corticospinal output and the output from the motoneurone pool. For example, recent studies have revealed that the efficacy of the human corticospinal connection with motoneurones undergoes activity-dependent changes which influence the size of voluntary contractions. Hence, corticospinal drives must be sculpted continuously to compensate for the changing functional efficacy of the descending systems which activate the motoneurones. This highlights the need for proprioceptive monitoring of movements to ensure their accurate execution.     

Stability of maps of human motor cortex made with transcranial magnetic stimulation

Cortical representation maps derived by transcranial magnetic stimulation (TMS) are often used, inter alia, in studying the plasticity of the brain. Parameters such as map area, map volume, optimal stimulation site and centre of gravity are commonly used to quantify changes in the topography of the motor cortex. However, reports on the stability of these parameters over time has not been conclusive. In the present study, the areas of the scalp from which responses were evoked from corticospinal cells projecting to three intrinsic hand muscles were systematically mapped with TMS at intervals of 24 hours, one week and two weeks from eight normal subjects. The area, "volume" and centre of gravity of these maps did not change significantly over this period. It is concluded that mapping with TMS is suitable for studies which aim to study the effect of various interventions on the cortical representation of individual muscles in human subjects.     

Motor cortical organization in an adult with hemimegalencephaly and late onset epilepsy

Hemimegalencephaly is a rare brain malformation whose physiology is largely obscure. In a single patient, we studied motor cortex using several transcranial magnetic stimulation variables testing cortical excitability, and mapping motor area. The megalencephalic hemisphere showed an enlargement of cortical motor map with abnormal axonal orientation and an excess spread of corticospinal excitation, associated with multiple defects of cortical inhibition. TMS gave new information on the anatomic/functional features and epileptogenesis in this complex and physiologically obscure syndrome.     

Functional reorganisation of the corticomotor projection to the hand in skilled racquet players

While it is known that relatively rapid changes in functional representation may occur in the human sensorimotor cortex in short-term motor-learning studies, there have been few studies of changes in organisation of the corticomotor system associated with the long-term acquisition of motor skills. In the present study, we have used transcranial magnetic stimulation (TMS) to investigate the corticomotor projection to the hand in a group of elite racquet players, who have developed and maintained a high level of skill over a period of many years, and have compared the findings with those in a group of social players and a group of non-playing control subjects. Increased motor-evoked-potential (MEP) amplitudes and shifts in the cortical motor maps for the playing hand were found in all of the elite players and cortical motor thresholds were reduced in some players, whereas in the social players all parameters were within the normal range. The findings in the elite players are interpreted as being indications of a process of functional reorganisation with the motor cortex or corticomotor pathway that are associated with the acquisition and retention of complex motor skills.     

Contribution of transcranial magnetic stimulation to the understanding of cortical mechanisms involved in motor control

Transcranial magnetic stimulation (TMS) was initially used to evaluate the integrity of the corticospinal tract in humans non-invasively. Since these early studies, the development of paired-pulse and repetitive TMS protocols allowed investigators to explore inhibitory and excitatory interactions of various motor and non-motor cortical regions within and across cerebral hemispheres. These applications have provided insight into the intracortical physiological processes underlying the functional role of different brain regions in various cognitive processes, motor control in health and disease and neuroplastic changes during recovery of function after brain lesions. Used in combination with neuroimaging tools, TMS provides valuable information on functional connectivity between different brain regions, and on the relationship between physiological processes and the anatomical configuration of specific brain areas and connected pathways. More recently, there has been increasing interest in the extent to which these physiological processes are modulated depending on the behavioural setting. The purpose of this paper is (a) to present an up-to-date review of the available electrophysiological data and the impact on our understanding of human motor behaviour and (b) to discuss some of the gaps in our present knowledge as well as future directions of research in a format accessible to new students and/or investigators. Finally, areas of uncertainty and limitations in the interpretation of TMS studies are discussed in some detail.     

Dynamical changes in corticospinal excitability during imagery of unimanual and bimanual wrist movements in humans: a transcranial magnetic stimulation study

This study explored the dynamical changes in corticospinal excitability during the imagination of cyclical unimanual and bimanual wrist flexion-extension movements. Transcranial magnetic stimulation was applied over the left motor cortex to evoke motor evoked potentials in the right wrist flexor and extensor muscles. Findings provided evidence for increased reciprocal excitability changes during imagery of symmetrical in-phase movements as compared to asymmetrical (anti-phase) or unimanual movements. This suggests that in-phase movements may reinforce whereas anti-phase movements may reduce the temporal representation of the task in the corticospinal motor networks of the brain.     

Peripheral nerve conduction and central motor conduction after magnetic stimulation of the brain in myotonic dystrophy.

Central motor conduction time was calculated after magnetic stimulation of the brain in 15 patients with myotonic dystrophy and in 38 healthy voluntaries of the same age. Conventional electromyography and motor and sensory conduction velocities were also performed. Central motor conduction time from vertex to C8 was within the normal range in all patients whereas motor conduction velocity of the peripheral nerve and amplitude of the nerve evoked potentials were slightly reduced in 3 and 2 cases respectively, supporting peripheral nerve involvement in some subjects. Our results suggest that the reported central nervous system involvement in myotonic dystrophy, including the nonspecific white matter lesions showed by magnetic resonance imaging, would not affect the conduction of the corticospinal tracts. Magnetic stimulation on the motor cortex is a painless method to study the central nervous system and apports a satisfactory approximation to central motor pathways conduction.     

TMS-responses during anticipatory postural adjustment in bimanual unloading in humans

Transcranial magnetic brain stimulation (TMS) was used to assess the influence of the corticospinal system on motor output during forearm unloading in humans. Unloading was obtained either "passively" by the experimenter, or "actively" with the subjects' own contralateral arm. Anticipatory postural adjustments consisted of changes in the activity of a forearm flexor muscle prior to active unloading of the limb and acted to stabilize the forearm position. Motor evoked potentials (MEPs) were recorded in the forearm flexor at different times during active and passive unloading, static forearm loading, and during lifting of an equivalent weight by the contralateral arm while the ipsilateral forearm was statically loaded and held stationary. In active unloading, MEP amplitude decreased with the decrease of muscle activity. Passive unloading resulted in a similar decrease of MEP as with active unloading. During stationary forearm loading, the change in MEP corresponded to the degree of loading. If during static loading the contralateral arm has lifted a separate, equivalent weight, the amplitude of MEP decreased. A possible role of direct corticospinal volley and the motor command mediated by subcortical structures in anticipatory postural adjustments is discussed.     

A multiple streamline approach to high angular resolution diffusion tractography

Diffusion-weighted magnetic resonance imaging has the ability to map neuronal architecture by estimating the 3D diffusion displacement within fibrous brain structures. This approach has non-invasively been demonstrated in the human brain with diffusion tensor tractography. Despite its valuable application in neuroscience and clinical studies however, it faces an inherent limit in mapping fiber tracts through areas with intervoxel incoherence. Recent advances in high angular resolution diffusion imaging have surpassed this limit and have the ability to resolve the complex fiber intercrossing within each MR voxel. To connect the fiber tracts from a multi-fiber system, this study proposed a modified fiber assignment using the continuous tracking (MFACT) algorithm and a tracking browser to propagate tracts along complex diffusion profiles. The Q-ball imaging method was adopted to acquire the diffusion displacements. Human motor pathways with seed points from the internal capsule, motor cortex, and pons were studied respectively. The results were consistent with known anatomy and demonstrated the promising potential of the MFACT method in mapping the complex neuronal architecture in the human brain.     

The effects of inhibitory and facilitatory intracortical circuits on interhemispheric inhibition in the human motor cortex

Inhibitory and facilitatory intracortical pathways regulating motor cortical output can be studied non-invasively in humans with transcranial magnetic stimulation. These circuits include short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF). Stimulation of the motor cortex also inhibits the contralateral motor cortex (interhemispheric inhibition, IHI) at short (∼10 ms, IHI10) or long intervals (∼40 ms, IHI40). We investigated how SICI, ICF, and LICI influence IHI10 and IHI40. We hypothesize that intracortical circuits will have similar effects on IHI and cortical output neurons: SICI and LICI will decrease IHI, and ICF will increase it. Motor evoked potentials were recorded from the first dorsal interosseous muscles bilaterally in 10 healthy subjects. We compared IHI10 and IHI40 alone to IHI10 and IHI40 elicited in the presence of SICI, ICF, or LICI. Our results showed that SICI and LICI reduced IHI10, IHI40 and corticospinal output to a similar degree. ICF increased corticospinal output but had no effect on either IHI10 or IHI40. The different effects of ICF on corticospinal excitability and IHI suggest the transcallosal fibres mediating IHI and the corticospinal output system arise from different neuronal populations. SICI and LICI produce more global inhibition with similar effects on the transcallosal and descending corticospinal circuits.     

Comparison of motor effects following subcortical electrical stimulation through electrodes in the globus pallidus internus and cortical transcranial magnetic stimulation

Current concepts of transcranial magnetic stimulation (TMS) over the primary motor cortex are still under debate as to whether inhibitory motor effects are exclusively of cortical origin. To further elucidate a potential subcortical influence on motor effects, we combined TMS and unilateral subcortical electrical stimulation (SES) of the corticospinal tract. SES was performed through implanted depth electrodes in eight patients treated with deep brain stimulation (DBS) for severe dystonia. Chronaxie, conduction velocity (CV) of the stimulated fibres and poststimulus time histograms of single motor unit recordings were calculated to provide evidence of an activation of large diameter myelinated fibres by SES. Excitatory and inhibitory motor effects recorded bilaterally from the first dorsal interosseus muscle were measured after SES and focal TMS of the motor cortex. This allowed us to compare motor effects of subcortical (direct) and cortical (mainly indirect) activation of corticospinal neurons. SES activated a fast conducting monosynaptic pathway to the alpha motoneuron. Motor responses elicited by SES had significantly shorter onset latency and shorter duration of the contralateral silent period compared to TMS induced motor effects. Spinal excitability as assessed by H-reflex was significantly reduced during the silent period after SES. No ipsilateral motor effects could be elicited by SES while TMS was followed by an ipsilateral inhibition. The results suggest that SES activated the corticospinal neurons at the level of the internal capsule. Comparison of SES and TMS induced motor effects reveals that the first part of the TMS induced contralateral silent period should be of spinal origin while its later part is due to cortical inhibitory mechanisms. Furthermore, the present results suggest that the ipsilateral inhibition is predominantly mediated via transcallosal pathways.This paper is dedicated to Bernd-Ulrich Meyer, who died in a plane accident     

White matter integrity of motor connections related to training gains in healthy aging

Impaired motor skill acquisition is a feature of older age. Acquisition of new motor skills requires the interplay between different cortical motor areas. Using diffusion tensor imaging we reconstructed cortico-cortical connections between the primary motor cortex (M1) and secondary motor areas in 11 older and 11 young participants who took part in a motor skill acquisition paradigm with the nondominant left hand. Examining the extent to which tract-related integrity correlated with training gains we found that white matter integrity of fibers connecting contralateral M1 with both contralateral (r = 0.85) and ipsilateral supplementary motor areas (r = 0.92) were positively associated in old participants. Also, fibers connecting contralateral M1 with ipsilateral dorsal premotor (r = 0.82) and fibers connecting ipsilateral dorsal premotor and supplementary motor area (r = 0.88) were positively related to skill acquisition (all p < 0.05). A similar structure-behavior relationship was not present in the young control subjects suggesting a critical role of brain structural integrity for motor learning in healthy aging.     

Neural correlates of encoding and expression in implicit sequence learning

It has been shown that high-frequency repetitive transcranial magnetic stimulation (rTMS) to the human primary motor hand area (M1-HAND) can induce a lasting increase in corticospinal excitability. Here we recorded motor evoked potentials (MEPs) from the right first dorsal interosseus muscle to investigate how sub-threshold high-frequency rTMS to the M1-HAND modulates cortical and spinal excitability. In a first experiment, we gave 1500 stimuli of 5 Hz rTMS. At an intensity of 90% of active motor threshold, rTMS produced no effect on MEP amplitude at rest. Increasing the intensity to 90% of resting motor threshold (RMT), rTMS produced an increase in MEP amplitude. This facilitatory effect gradually built up during the course of rTMS, reaching significance after the administration of 900 stimuli. In a second experiment, MEPs were elicited during tonic contraction using weak anodal electrical or magnetic test stimuli. 1500 (but not 600) conditioning stimuli at 90% of RMT induced a facilitation of MEPs in the contracting FDI muscle. In a third experiment, 600 conditioning stimuli were given at 90% of RMT to the M1-HAND. Using two well-established conditioning-test paradigms, we found a decrease in short-latency intracortical inhibition (SICI), and a facilitation of the first peak of facilitatory I-waves interaction (SICF). There was no correlation between the relative changes in SICI and SICF. These results demonstrate that subthreshold 5 Hz rTMS can induce lasting changes in specific neuronal subpopulations in the human corticospinal motor system, depending on the intensity and duration of rTMS. Short 5 Hz rTMS (600 stimuli) at 90% of RMT can selectively shape the excitability of distinct intracortical circuits, whereas prolonged 5 Hz rTMS (900 stimuli) provokes an overall increase in excitability of the corticospinal output system, including spinal motoneurones.     

Excitability of corticospinal neurons during tonic muscle contractions in man

Summary A magnetic stimulus applied to the human scalp over the motor cortex causes a short latency contraction of contralateral limb muscles. This is presumed to result from the indirect excitation of corticospinal neurons with monosynaptic connections to motoneurons. The excitability of these cortical neurons can be estimated from the magnitude of the postsynaptic potentials produced in spinal motoneurons by a given magnetic stimulus. In man the characteristics of these postsynaptic potentials can be derived from changes in the firing probability of single motor units. When a subject increases the level of a sustained voluntary contraction the excitability of the corticospinal neurons estimated in this way becomes less. We conclude that the additional synaptic input to motoneurons required to maintain a stronger muscle contraction comes from fiber systems other than the population of fast corticospinal neurons activated by magnetic stimulation.     

Reorganisation of descending motor pathways in patients after hemispherectomy and severe hemispheric lesions demonstrated by magnetic brain stimulation

Summary Numerous clinical studies on patients after hemispherectomy (HS) have provided clear evidence that two distinct groups can be recognized on the basis of the quality of their motor functions after operation. One of these consists of cases where HS was performed after normal brain maturation, the other of patients where the removed hemisphere was damaged early in life. The post-operative motor function has been found to be much better in the latter group. In the present paper it is demonstrated that in contrast to normal subjects ipsilateral compound muscle action potentials (CMAPs) induced by magnetic stimulation of the one intact motor cortex are present in patients after HS. The amplitudes of ipsilateral CMAPs in the muscles roughly correlate with their individual residual motor capacities and show a proximo-distal gradient. In patients with early brain damage prior to HS, CMAPs had short latencies and large amplitudes, whereas in patients with later acquired brain damage prior to HS, CMAPs had long latencies and small amplitudes. It is suggested that reinforcement of the ipsilateral corticospinal pathway may be responsible for residual motor functions in patients with early brain damage, whereas in patients with later acquired brain damage cortico-reticulospinal pathways may play a dominant role in ipsilateral motor control.     

Shaping the excitability of human motor cortex with premotor rTMS

Recent studies have shown that low-frequency repetitive transcranial magnetic stimulation (rTMS) to the left dorsal premotor cortex has a lasting influence on the excitability of specific neuronal subpopulations in the ipsilateral primary motor hand area (M1 _HAND ). Here we asked how these premotor to motor interactions are shaped by the intensity and frequency of rTMS and the orientation of the stimulating coil. We confirmed that premotor rTMS at 1 Hz and an intensity of 90% active motor threshold (AMT) produced a lasting decrease in corticospinal excitability probed with single-pulse TMS over the left M1 _HAND . Reducing the intensity to 80% AMT increased paired-pulse excitability at an interstimulus interval (ISI) of 7 ms. Opposite effects occurred if rTMS was given at 5 Hz: at 90% AMT, corticospinal excitability increased; at 80% AMT, paired-pulse excitability at ISI = 7 ms decreased. No effects were seen if rTMS was applied at the same intensities to prefrontal or primary motor cortices. These findings indicate that the intensity of premotor rTMS determines the net effect of conditioning on distinct populations of neurones in the ipsilateral M1 _HAND , but it is the frequency of rTMS that determines the direction of the induced change. By selecting the appropriate intensity and frequency, premotor rTMS allows to induce a predictable up- or down-regulation of the excitability in distinct neuronal circuits of human M1 _HAND .     

Postnatal development of corticospinal postsynaptic action

The corticospinal system has a delayed and prolonged postnatal development. In the cat, lesion, inactivation, or stimulation of the system influence motor output minimally when corticospinal (CS) terminals have an immature topographic pattern but produce robust effects immediately after developing the mature pattern by weeks 6-7. In this study, we directly tested if the delay in expression of cortical motor functions is due to the inability of the corticospinal synapse to activate spinal neurons. We stimulated corticospinal axons in the pyramid and recorded evoked field potentials from the surface of the cervical spinal cord and locally from within the gray matter in anesthetized cats during development and in adults. Pyramidal stimulation in animals between week 4 and maturity evoked an initial corticospinal surface volley followed by a postsynaptic field response. Depth recordings from the superficial dorsal horn to the ventral white matter showed that local pre- and postsynaptic field potentials could be recorded over the full extent of the gray matter in 4- to 5-wk animals but were restricted to the intermediate zone in older animals and adults. Dorsoventral refinement of CS field potentials parallels anatomical refinement of individual CS axon terminals shown in our earlier studies. Our present findings indicate that the developing corticospinal system could influence the excitability of virtually the entire contralateral gray matter before cortical motor functions are expressed. Given the importance of activity-dependent axon terminal refinement, this capacity for activating spinal neurons during early postnatal life could play an important role in development of CS circuit connectivity.