Riccardo Mazzocchio

Influence of interhemispheric interactions on motor function in chronic stroke

In patients with chronic stroke, the primary motor cortex of the intact hemisphere (M1intact hemisphere) may influence functional recovery, possibly through transcallosal effects exerted over M1 in the lesioned hemisphere (M1lesioned hemisphere). Here, we studied interhemispheric inhibition (IHI) between M1intact hemisphere and M1lesioned hemisphere in the process of generation of a voluntary movement by the paretic hand in patients with chronic subcortical stroke and in healthy volunteers. IHI was evaluated in both hands preceding the onset of unilateral voluntary index finger movements (paretic hand in patients, right hand in controls) in a simple reaction time paradigm. IHI at rest and shortly after the Go signal were comparable in patients and controls. Closer to movement onset, IHI targeting the moving index finger turned into facilitation in controls but remained deep in patients, a finding that correlated with poor motor performance. These results document an abnormally high interhemispheric inhibitory drive from M1intact hemisphere to M1lesioned hemisphere in the process of generation of a voluntary movement by the paretic hand. It is conceivable that this abnormality could adversely influence motor recovery in some patients with subcortical stroke, an interpretation consistent with models of interhemispheric competition in motor and sensory systems.

Formation of a motor memory by action observation

Mirror neurons discharge with both action observation and action execution. It has been proposed that the mirror neuron system is instrumental in motor learning. The human primary motor cortex (M1) displays mirror activity in response to movement observation, is capable of forming motor memories, and is involved in motor learning. However, it is not known whether movement observation can lead directly to the formation of motor memories in the M1, which is considered a likely physiological step in motor learning. Here, we used transcranial magnetic stimulation (TMS) to show that observation of another individual performing simple repetitive thumb movements gives rise to a kinematically specific memory trace of the observed motions in M1. An extended period of observation of thumb movements that were oriented oppositely to the previously determined habitual directional bias increased the probability of TMS-evoked thumb movements to fall within the observed direction. Furthermore, the acceleration of TMS-evoked thumb movements along the principal movement axis and the balance of excitability of muscle representations active in the observed movements were altered in favor of the observed movement direction. These findings support a role for the mirror neuron system in memory formation and possibly human motor learning.

Transcallosal inhibition in chronic subcortical stroke

Movements of the paretic hand in patients with chronic subcortical stroke are associated with high interhemispheric inhibition (IHI) targeting the motor cortex in the lesioned hemisphere relative to healthy controls. The purpose of this investigation was to determine whether this abnormality also involves IHI operating during movements of the non-paretic hand. Here, we studied IHI in the process of generation of voluntary index finger movements by the paretic and non-paretic hands in a simple reaction time paradigm in a group of patients with chronic subcortical stroke. With movements of the non-paretic index finger, IHI targeting the contralateral primary motor cortex ((c)M1) decreased progressively to turn into facilitation at around movement onset, similar to healthy controls. In contrast, movements of the paretic index finger resulted in significantly deeper inhibition at all premovement timings relative to the non-paretic hand. In conclusion, these results document a deeper premovement IHI with paretic than non-paretic hand movements of patients with chronic subcortical stroke, a possible mechanism underlying deficits in motor control.

Intermanual Differences in Movement-related Interhemispheric Inhibition

Interhemispheric inhibition (IHI) between motor cortical areas is thought to play a critical role in motor control and could influence manual dexterity. The purpose of this study was to investigate IHI preceding movements of the dominant and nondominant hands of healthy volunteers. Movement-related IHI was studied by means of a double-pulse transcranial magnetic stimulation protocol in right-handed individuals in a simple reaction time paradigm. IHI targeting the motor cortex contralateral (IHIc) and ipsilateral (IHIi) to each moving finger was determined. IHIc was comparable after the go signal, a long time preceding movement onset, in both hands. Closer to movement onset, IHIc reversed into facilitation for the right dominant hand but remained inhibitory for left nondominant hand movements. IHIi displayed a nearly constant inhibition with a trough early in the premovement period in both hands. In conclusion, our results unveil a more important modulation of interhemispheric interactions during generation of dominant than nondominant hand movements. This modulation essentially consisted of a shift from a balanced IHI at rest to an IHI predominantly directed toward the ipsilateral primary motor cortex at movement onset. Such a mechanism might release muscles from inhibition in the contralateral primary motor cortex while preventing the occurrence of the mirror activity in ipsilateral primary motor cortex and could therefore contribute to intermanual differences in dexterity.

Evidence for two concurrent inhibitory mechanisms during response preparation

Inhibitory mechanisms are critically involved in goal-directed behaviors. To gain further insight into how such mechanisms shape motor representations during response preparation, motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) and H-reflexes were recorded from left hand muscles during choice reaction time tasks. The imperative signal, which indicated the required response, was always preceded by a preparatory cue. During the postcue delay period, left MEPs were suppressed when the left hand had been cued for the forthcoming response, suggestive of a form of inhibition specifically directed at selected response representations. H-reflexes were also suppressed on these trials, indicating that the effects of this inhibition extend to spinal circuits. In addition, left MEPs were suppressed when the right hand was cued, but only when left hand movements were a possible response option before the onset of the cue. Notably, left hand H-reflexes were not modulated on these trials, consistent with a cortical locus of inhibition that lowers the activation of task-relevant, but nonselected responses. These results suggest the concurrent operation of two inhibitory mechanisms during response preparation: one decreases the activation of selected responses at the spinal level, helping to control when selected movements should be initiated by preventing their premature release; a second, upstream mechanism helps to determine what response to make during a competitive selection process.

Plastic changes in the human H-reflex pathway at rest following skillful cycling training

OBJECTIVEnThe spinal cord is capable of activity-dependent plasticity, but the extent of its participation in human motor learning is not known. Here, we tested the hypothesis that acquisition of a locomotor-related skill modulates the pathway of the H-reflex, a measure of spinal cord excitability that is susceptible to plastic changes.nnnMETHODSnSubjects were tested on their ability to establish a constant cycling speed on a recumbent bike despite frequent changes in pedal resistance. The coefficient of variation of speed (CV(speed)) measured their ability to acquire this skill (decreasing CV(speed) with training reflects performance improvements). Soleus H-reflexes were taken at rest before and after cycling.nnnRESULTSnAbility to establish a target speed increased and H-reflex size decreased more after cycling training involving frequent changes in pedal resistance that required calibrated locomotor compensatory action than with training involving constant pedal resistances and lesser compensation. The degree of performance improvement correlated with the reduction in the amplitude of the H-reflex.nnnCONCLUSIONSnSkillful establishment of a constant cycling speed despite changing pedal resistances is associated with persistent modulation of activity in spinal pathways.nnnSIGNIFICANCEnRecalibration of activity in the H-reflex pathway may be part of the control strategy required for locomotor-related skill acquisition.

Modulation of H-reflex excitability by tetanic stimulation

OBJECTIVEnThis study investigated a strategy to elicit reversible facilitation of the soleus monosynaptic H-reflex in humans using a modified tetanic stimulation technique.nnnMETHODSnInterventional tetanic stimulation (ITS) was applied to the tibial nerve in the popliteal fossa, and soleus H-reflexes were recorded before and after stimulation in 15 healthy volunteers.nnnRESULTSnITS resulted in significantly increased soleus H-reflex amplitudes that outlasted the stimulation period by approximately 16 min. The effect of ITS on soleus motor evoked potentials to transcranial magnetic stimulation and on somatosensory evoked potentials to tibial nerve stimulation was also investigated; no significant changes were found.nnnCONCLUSIONSnITS produced a reversible increase in H-reflexes in the absence of changes in motor evoked potential or somatosensory evoked potential that outlasted the intervention period for up to 16 min.nnnSIGNIFICANCEnThis technique may be used in future studies to investigate whether the induced increased H-reflex excitability influences locomotion.

Influence of Interhemispheric Interactions on Paretic Hand Movement in Chronic Subcortical Stroke

In patients with chronic stroke, the primary motor cortex of the intact hemisphere (M1intact) may influence functional recovery, possibly through transcallosal effects exerted over Ml in the lesioned hemisphere (Mllesioned). Here, we studied interhemispheric inhibition (IHI) between Mlintact and M1lesioned in the process of generation of a voluntary movement by the paretic hand in patients with chronic subcortical stroke and in healthy volunteers. IHI was evaluated in both hands preceding the onset of unilateral voluntary index finger movements (paretic hand in patients, right hand in controls) in a simple reaction time paradigm. IHI at rest and shortly after the Go signal were comparable in patients and controls. Closer to movement onset, IHI targeting the moving index finger turned into facilitation in controls but inhibition still continued in patients, a finding that correlated with poor motor performance. IHI targeting the resting finger remained deep all through the reaction time. In case of intact hand movement, IHI targeting the moving fingers showed similar facilitation with that in control subjects. These results suggest an abnormally high interhemispheric inhibitory drive from M1intact to M1lesioned in the paretic hand movement. It is conceivable that this abnormality could adversely influence motor recovery in some patients with subcortical stroke.