Julie Duque

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.

Encoding a motor memory in the older adult by action observation.

The ability of motor training to encode a motor memory is reduced in older adults. Here, we tested the hypothesis that training-dependent memory encoding, an issue of relevance in neurorehabilitation, is enhanced in elder individuals by action observation which alone can contribute to learning processes. A group of 11 healthy older adults participated in this study, which consisted of three randomized counterbalanced sessions on different days testing the effects of motor training (MT) alone, action observation (AO) alone, and a combination of both (MT + AO) on motor memory encoding. The combination of MT + AO formed a motor memory in the primary motor cortex and differentially modulated motor cortical excitability in muscles that were agonist and antagonist with respect to the training task, but MT or AO alone did not. These results suggest that action observation can enhance the effects of motor training on memory encoding protocols in the older adult, possibly through Hebbian modulation of intracortical excitatory mechanisms.

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.

Dissociating the Role of Prefrontal and Premotor Cortices in Controlling Inhibitory Mechanisms during Motor Preparation

Top-down control processes are critical to select goal-directed actions in flexible environments. In humans, these processes include two inhibitory mechanisms that operate during response selection: one is involved in solving a competition between different response options, the other ensures that a selected response is initiated in a timely manner. Here, we evaluated the role of dorsal premotor cortex (PMd) and lateral prefrontal cortex (LPF) of healthy subjects in these two forms of inhibition by using an innovative transcranial magnetic stimulation (TMS) protocol combining repetitive TMS (rTMS) over PMd or LPF and a single pulse TMS (sTMS) over primary motor cortex (M1). sTMS over M1 allowed us to assess inhibitory changes in corticospinal excitability, while rTMS was used to produce transient disruption of PMd or LPF. We found that rTMS over LPF reduces inhibition associated with competition resolution, whereas rTMS over PMd decreases inhibition associated with response impulse control. These results emphasize the dissociable contributions of these two frontal regions to inhibitory control during motor preparation. The association of LPF with competition resolution is consistent with the role of this area in relatively abstract aspects of control related to goal maintenance, ensuring that the appropriate response is selected in a variable context. In contrast, the association of PMd with impulse control is consistent with the role of this area in more specific processes related to motor preparation and initiation.

Evaluation of handgrip force from EMG measurements.

A series of experiments were performed in order to investigate whether estimates of handgrip force could be derived with fair accuracy from surface EMG levels recorded on the finger flexors of the forearm, taking into account the position of the wrist in the flexion-extension plane and in the ulnar-radial deviation plane. Handgrip forces (on a JAMAR dynamometer) and corresponding surface EMG levels (on the finger flexors of the forearm) were recorded for 20 subjects in 11 postures of the wrist and for 30% and 70% of the MVC in neutral posture. A mathematical empirical model was developed using multiple non-linear regression analysis. Although quite simple, it provides very reliable results, the correlation coefficient between predicted and observed forces being 0.895. Its use must, however, be restricted to work situations where: (a) the hand efforts are of the same type and involve the same muscles as those exerted on the dynamometer; (b) the hand is in neutral pro-supination; and (c) no voluntary effort is exerted by the wrist flexors except for maintaining the wrist posture.

Transcranial magnetic stimulation of posterior parietal cortex affects decisions of hand choice

Deciding which hand to use for an action is one of the most frequent decisions people make in everyday behavior. Using a speeded reaching task, we provide evidence that hand choice entails a competitive decision process between simultaneously activated action plans for each hand. We then show that single-pulse transcranial magnetic stimulation to the left posterior parietal cortex biases this competitive process, leading to an increase in ipsilateral, left hand reaches. Stimulation of the right posterior parietal cortex did not alter hand choice, suggesting a hemispheric asymmetry in the representations of reach plans. These results are unique in providing causal evidence that the posterior parietal cortex is involved in decisions of hand choice.

Influence of somatosensory input on interhemispheric interactions in patients with chronic stroke

Background. Ischemia-induced cutaneous anesthesia of the healthy hand in patients with chronic stroke elicits transient improvements of motor performance in the contralateral, paretic hand. Objective. The present study was designed to investigate one of the possible mechanisms underlying this effect. Methods. The authors evaluated the effects of transient ischemic cutaneous anesthesia of the healthy hand (target intervention) and healthy foot (control intervention) on transcranial magnetic stimulation-induced interhemispheric inhibition from the contralesional onto the ipsilesional primary motor cortex (M1). Ten subjects with chronic, predominantly subcortical stroke with motor impairment were assessed. Results. Cutaneous anesthesia of the intact hand but not the intact leg resulted in reduction of the inhibitory drive from the contralesional to the ipsilesional M1 both at rest and immediately preceding movements of the paretic hand. Changes in premovement interhemispheric inhibition showed a trend for correlation with improvements in finger-tapping speed in the paretic hand. Conclusion. The findings suggest that modulation of interhemispheric inhibitory interactions between the contralesional and ipsilesional M1, either primarily or secondary to intrahemispheric excitability changes in either hemisphere, may contribute to performance improvements with cutaneous anesthesia of the intact hand. The present study provides additional insight into the mechanisms by which rehabilitative interventions focused on training one hand and restraining the other may operate after chronic stroke.